JCS/JACR 2021 Guideline on Rehabilitation in Patients With Cardiovascular Disease

Abbreviations

CR	cardiac rehabilitation
1RM	1-repetition maximum
6MWD	6-minute walk distance
ACC (F)	American College of Cardiology (Foundation)
ACS	acute coronary syndrome
ADL	activities of daily living
AF	atrial fibrillation
AHA	American Heart Association
AMI	acute myocardial infarction
AT	anaerobic threshold
BMI	body mass index
BNP	brain natriuretic peptide / B-type natriuretic peptide
CABG	coronary artery bypass grafting
CAD	coronary artery disease
CHD	congenital heart disease
CKD	chronic kidney disease
CORE	cardio-oncology rehabilitation
COPD	chronic obstructive pulmonary disease
CONUT	Controlling Nutritional Status
CPX	cardiopulmonary exercise testing
CRT	cardiac resynchronization therapy
CRT-D	cardiac resynchronization therapy defibrillator
CRT-P	cardiac resynchronization therapy pacemaker
CVD	cardiovascular disease
CVRF	cardiovascular risk factor
eGFR	estimated glomerular filtration rate
EOV	exercise oscillatory ventilation
ESC	European Society of Cardiology
GLIM	Global Leadership Initiative on Malnutrition
GNRI	Geriatric Nutritional Index
HFpEF	heart failure with preserved ejection fraction
HFrEF	heart failure with reduced ejection fraction
HIIT	high-intensity interval training
HR	heart rate
HRR	heart rate reserve
HRQOL	health-related quality of life
IADL	instrumental activities of daily living
ICD	implantable cardioverter defibrillator
LVAS/LVAD	left ventricular assist system/device
LVEF	left ventricular ejection fraction
MET	metabolic equivalent
MI	myocardial infarction
MNA®	Mini Nutritional Assessment
MNA®-SF	Mini Nutritional Assessment-Short Form
PAD	peripheral arterial disease
PCI	percutaneous coronary intervention
peak V̇O2	peak oxygen uptake
PH	pulmonary hypertension
PVCs	premature ventricular contraction
QOL	quality of life
RCT	randomized controlled trial
RPE	rating of perceived exertion
SGA	Subjective Global Assessment
STEMI	ST elevation myocardial infarction
TG	triglyceride
TAVI	transcatheter aortic valve implantation
VAD	ventricular assist device
V̇CO2	carbon dioxide output
V̇E	minute ventilation
V̇E/V̇CO2	ventilatory equivalent for carbon dioxide
V̇E vs. V̇CO2 slope	minute ventilation vs. carbon dioxide output slope
V̇O2	oxygen uptake
V̇O2/HR	oxygen pulse

Introduction

Eight years have passed since the publication of the only guideline on cardiac rehabilitation (CR) in Japan, “Guidelines for rehabilitation in patients with cardiovascular disease (JCS 2012)” (Chair: Ryuji Nohara).¹ In that time, the situation surrounding CR, including cardiovascular care in Japan, has changed dramatically. Specifically, compared with 2012, the following changes have occurred: (1) new findings on CR and exercise training, including transcatheter aortic valve implantation (TAVI) and pulmonary hypertension (PH), have emerged, (2) CR is becoming highly recognized as a disease management program after discharge from acute care hospitals due to the shortening of hospital stay and the increasing number of older patients with heart failure (HF), (3) several clinical guidelines, such as the “Guideline on diagnosis and treatment of acute and chronic heart failure” have been revised, but descriptions are inconsistent from guideline to guideline, (4) due to revision of the Japanese medical reimbursement system, the criteria that CR facilities must follow have changed, causing a discrepancy between the guidelines and the medical practice.

The main points of this revision are as follows.

(1) From the viewpoint that comprehensive CR is important in daily clinical practice, in addition to exercise training, we have added sections on nutrition and diet therapy, patient education, and disease management as well as psychological interventions.

(2) With a growing number of older patients with cardiovascular disease (CVD), we have listed the targets of basic physical function, in particular muscle strength and walking ability of lower limbs; as important goals; sarcopenia and frailty are also discussed.

(3) With the growing number of HF patients, we have included HF as a target disease, and added sections on rehabilitation after TAVI, device implantation, and endovascular treatment of aortic disease and that for PH.

(4) As a special patient group, older cardiac patients (including super-aged patients) are listed as an independent section. Additionally we have completely rewritten the sections on rehabilitation protocol during intravenous inotropic drug administration, rehabilitation after implantation of a ventricular assist device (in particular, the implantable type), and rehabilitation after heart transplantation. We have also explained and incorporated onco-cardiology as a focus, because it is becoming a topic in cardiology practice, and the role of CR is attracting attention in this field.

(5) As for future issues and perspectives, we have included the theoretically ideal CR in the recovery phase, and the relationship with home medical care, community-based comprehensive care, and palliative care. We have also added a section on telemedicine as a new approach to outpatient and maintenance CR, given the new coronavirus epidemic.

After the first meeting of the Guideline Development Group for the JCS/JACR “2021 Guideline on rehabilitation in patients with cardiovascular disease” in March 2019, the initial draft of this guideline was revised three times by the group members and collaborators. In light of the comments from external reviewers, the guideline was finalized after discussions at the group meeting. This guideline was based on the latest guidelines from Europe and the USA, while incorporating evidence and actual clinical experience in Japan, with the aim of becoming a standard guideline for CR. We express our gratitude again to all involved and hope that this guideline will make a significant contribution to CR medicine in Japan and be useful to many medical professionals in their daily clinical practice.

Classes of Recommendations and Levels of Evidence

The classes of recommendations (COR) and levels of evidence (LOE) in this guideline were determined by the authors based on the literature published to date, and finally assessed by peer review of the members and external evaluators; the descriptions are in accordance with the conventional methods of labeling COR and LOE (Tables 1,2). In the cardiovascular field in Japan, the conventional classifications of COR and LOE are widely used, and are consistent with the overseas descriptors. In contrast, the Medical Information Network Distribution Service (MINDS), a medical information service operated by the Japan Council for Quality Health Care, describes the MINDS grades of recommendations and MINDS levels of evidence differently in the “MINDS handbook for clinical practice guideline development 2007” (Tables 3,4).² Therefore, in this guideline, the MINDS Grades of Recommendations and MINDS Levels of Evidence are provided for reference only.

Table 1. Classes of Recommendations

Class I	Evidence and/or general agreement that a given procedure or treatment is effective and useful
Class IIa	Weight of evidence/opinion is in favor of usefulness/efficacy
Class IIb	Usefulness/efficacy is less well established by evidence/opinion
Class III (No benefit)	Evidence or general agreement that the given procedure or treatment is not useful/effective
Class III (Harm)	Evidence or general agreement that the given procedure or treatment is harmful

Table 2. Levels of Evidence

Level A	Data derived from multiple randomized clinical trials or meta-analyses
Level B	Data derived from a single randomized clinical trial or large non-randomized clinical trials
Level C	Consensus of opinion of the experts and/or small clinical trials (including retrospective trials, registries)

Table 3. MINDS Grades of Recommendations

Grade A	Strongly recommended and supported by strong evidence
Grade B	Recommended with moderately strong supporting evidence
Grade C1	Recommended despite the lack of supporting evidence
Grade C2	Not recommended because of the absence of supporting evidence
Grade D	Not recommended as evidence indicates that the treatment is ineffective or even harmful

The grades of recommendations are based on a comprehensive assessment of the level and quantity of evidence, variation of conclusion, level of clinical efficacy, clinical applicability, and evidence of harm and cost. (Adapted from MINDS Handbook for Clinical Practical Guideline Development, 2007, p.16.²)

Table 4. MINDS Levels of Evidence (Levels of Evidence in the Literature on Treatment)

I	Systematic review/meta-analysis of randomized controlled trials
II	One or more randomized controlled trial
III	Non-randomized controlled trials
IVa	Analytical epidemiological studies (cohort studies)
IVb	Analytical epidemiological studies (case-control studies, cross-sectional studies)
V	Descriptive research (case reports, case series)
VI	Not based on patient data, or based on opinions from a specialist committee or individual specialists

(Adapted from MINDS Handbook for Clinical Practice Guideline Development, 2007, p.16² with modifications.)

I. Definition, Components, and Phase-Based Classification

1. Definition

The title of this guideline is “JCS/JACR 2021 guideline on rehabilitation in patients with cardiovascular disease.” The term “cardiovascular rehabilitation” has been used consistently since the revision in 2007, but because the definition of cardiac rehabilitation (CR) clearly states that cardiovascular diseases (CVDs) are the target of CR, and “cardiac rehabilitation (CR)” is widely used in daily clinical practice and related academic societies, the term “cardiac rehabilitation (CR)” is used in this revision.

The Japanese Society of Cardiac Rehabilitation defines CR as follows: “Cardiac rehabilitation refers to a long-term, multifaceted, comprehensive program designed to optimize a cardiac patient’s physical, psychological, social, and vocational status, in addition to stabilizing, slowing, or even reversing the progression of the underlying atherosclerotic or heart failure processes, thereby reducing recurrence, rehospitalization and mortality and enabling patients to live comfortably and actively. Cardiac rehabilitation programs include ‘medical assessment, prescribed exercise training, coronary risk factor modification, patient education, counseling and optimal medical therapy’ for individual patients, which are provided by a multi-disciplinary team in a coordinated manner.”

Recent trends in the treatment of CVDs in Japan include: (1) a decrease in in-hospital mortality rates for acute myocardial infarction (AMI) and acute heart failure (HF),³ (2) an increase in patients with multiple comorbidities such as chronic HF, atrial fibrillation (AF), diabetes mellitus, chronic kidney disease (CKD), and dementia,⁴ (3) an increase in older cardiac patients with the complication of frailty, (4) progression of disuse syndrome and the need for nursing care due to prolonged bed rest,⁵ (5) an increase in readmissions due to inadequate management after hospital discharge,⁴ and (6) an increase in national health care expenditure.³ Considering these current circumstances, we need to focus not only on reducing the acute mortality, but also on improving quality of life (QOL) after discharge and preventing rehospitalization.

2. Components

The components of CR include the following conventional aspects: (1) medical evaluation of the patient’s condition and severity, (2) exercise prescription and exercise training based on medical evaluation, (3) improvement of coronary risk factors and patient education, and (4) counseling on psychosocial factors and on returning to work.⁶ Also, (5) disease management. “Prevention of hospital readmission, prevention of frailty, and improvement of depression” are also important objectives of CR.⁷ The disease management program consists of interventions by a multidisciplinary medical team, including (1) provision of standard medical care based on practice guidelines, (2) thorough self-management (self-care) through “patient education, lifestyle intervention, and motivation”, and (3) early detection of disease progression through telephone and home monitoring. These interventions have been reported to reduce rehospitalization for HF and improve life expectancy.^8,9 Considering the current situation of the limitations of advanced acute care, outpatient CR is important as a comprehensive disease management program after hospital discharge.

3. Phase-Based Classification

CR is a comprehensive and long-term intervention program. Currently, it is thought that rehabilitation should be classified according to the form (monitoring level) and content, such as ambulation and return to social life, and is classified as “acute phase (phase I)” from the day of onset (surgery) to getting out of bed, “recovery phase (phase II)” after getting out of bed (early recovery phase, late recovery phase), and “maintenance phase (phase III)” after social return (Figure 1).¹⁰ It is important to note that the acute phase and early recovery phase were shortened in the 2000s, and the focus changed to lifelong prevention. CR is systematically performed not only as exercise training but also recurrence prevention with lifestyle interventions and correction of coronary risk factors, and it is expected to include a comprehensive disease management program from the acute phase to the chronic phase.

Figure 1.

Phase-based classification of cardiac rehabilitation (CR). (Adapted from Izawa, et al, 2019¹⁰ with modifications.)

3.1 Acute Phase (Phase I)

CR in the acute phase is performed under supervision in the intensive care unit, cardiac care unit or hospital ward. The goal of CR is to enable the patient to safely perform activities of daily living (ADL), such as eating, toileting, and bathing (independence in ADL), and to start secondary prevention education. In the treatment of AMI, a clinical pathway including acute CR is also used. Immediately after hospitalization for AMI or acute HF, or in the acute phase after cardiovascular surgery, treatment is aimed at achieving hemodynamic stability.

If bed rest is prolonged during this phase, exercise capacity will decline and frailty will progress. Therefore, an early mobilization program should be started from the bedside, in parallel with the acute treatment, leading to early exercise training. At the end of this phase, a 6-minute walk test is performed, and if the patient can walk more than 300 m, the program shifts from an ambulation program to an exercise training program. It is also important to provide patient education in parallel with the ambulation program. The patient’s understanding of his/her own condition will not only be useful for subsequent lifestyle interventions and management of coronary risk factors, but will also motivate the patient to engage in CR.

3.2 Recovery Phase (Phase II): Early and Late Recovery Phases

CR in the recovery phase is defined as the period from becoming ambulatory until the time when the condition stabilizes after social return. CR in the early recovery phase is started under supervision in the CR room during hospitalization, and is followed by supervised exercise training in the outpatient CR room after discharge. In late recovery phase CR, outpatient supervised exercise training and home unsupervised exercise training are combined; in low-risk patients, it is possible to perform only the unsupervised home exercise training. Eventually, patients are instructed to self-manage their exercise program. Exercise capacity is assessed by cardiopulmonary exercise testing (CPX), an exercise prescription is prepared based on the risk in terms of severity of illness, and then a treatment and CR plan is established. If CPX cannot be performed due to complications, low physical fitness, or low left ventricular function, exercise capacity should be confirmed by the 6-minute walk test.

For frail patients, after hospital discharge, their living environment, nursing care certification, and use of nursing care services should be confirmed. In addition, a counseling program for lifestyle modification and adherence to medication, assessment and management of comorbidity, and psychological counseling should be provided. It is not rare for patients with cardiac disease to be depressed after hospital discharge due to anxiety about their physical health, financial problems, and concerns about returning to work or sexual potency.¹¹ Regarding recovery phase CR, a comprehensive disease management program that includes exercise training, smoking cessation, diet therapy, appropriate treatment of coronary risk factors, as well as psychological evaluations, return-to-work counseling, and psychological support, are important. In addition, the importance of self-management to prevent recurrence should be explained to patients and their families, and information on treatment goals and the content of the recovery CR program should be shared within the multidisciplinary CR team and discussed at regular conferences. Counseling will be given on appropriate physical activity based on exercise capacity, and excessive or low activity should be adjusted to the appropriate activity level. If there are signs or findings that suggest exacerbation of medical condition/heart failure or excessive exercise load, the exercise prescription must be reviewed with consideration given to intensify the treatment.

3.3 Maintenance Phase (Phase III)

Maintenance CR should be performed throughout life, after social return. Self-health management, such as maintaining exercise capacity, lifestyle modification, and correction of coronary risk factors, acquired during recovery CR, will be the main focus. Considering the individual’s background, such as age, occupation, and physical activity level, a program tailored to the individual’s lifestyle is created at home or at a private exercise training facility. When referring to local institutions or clinics, a medical information sheet that includes the medical history, current cardiac function, prescriptions, and exercise program should be provided; later, a system that allows for periodic evaluation and review of the exercise program is needed.

In Japan, the numbers of patients with many comorbidities such as chronic HF, AF, diabetes, CKD, and dementia, as well as very old patients with heart disease complicated by frailty, are increasing.^4,5 It is a difficult issue to secure disease management and intervention for HF at the level of home care after the end of the CR insurance period (150 days), and close community medical cooperation, including home nursing, day care, and day services, is necessary.

II. Assessment of Physical Activity Capacity

1. Definition

Physical activity capacity is almost synonymous with maximal exercise capacity, exercise capacity, and exercise tolerance,¹² and is defined by both the maximal capacity of the cardiovascular system to deliver oxygen to the exercising muscle and the maximal capacity of skeletal muscle to utilize oxygen.¹³ In the absence of respiratory disease or anemia, the oxygen-carrying capacity to the exercising muscle is determined by the maximal cardiac output, the oxygen content of the arterial blood, and the ratio of blood flow to the exercising muscle to the maximal cardiac output.¹⁴ Therefore, physical activity capacity is evaluated by a perceived maximal stress, or a maximal exercise stress test that increases the work rate until the stress discontinuation criteria is met. In general, CPX is performed, and physical activity capacity is expressed as the oxygen uptake (V̇O₂) obtained at maximal load.

In patients with heart disease in particular, peak oxygen uptake (peak V̇O₂) is widely used as an indicator of exercise capacity and prognosis. Because the peak V̇O₂ becomes higher as the muscle mass mobilized for exercise increases (i.e., as body size increases), it is generally expressed by correcting according to body weight (expressed in mL/min/kg). Thus, exercise capacity may be underestimated in overweight subjects, and likewise, may be overestimated in highly lean subjects, so care must be taken when interpreting the results of CPX in these subjects. The peak V̇O₂ decreases with age in healthy adults and is lower in women than in men of the same age. Therefore, in CPX reports, peak V̇O₂ is usually expressed as mL/min/kg, which is the measured value divided by body weight, and is also expressed as % of the predicted value (standard value) calculated on the basis of age and sex.

2. Evaluation Method, Index (Table 5)

Table 5. Recommendations and Levels of Evidence for Assessment of Physical Activity Capacity and Physical Function in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Assessment of muscle strength
For patients with predicted muscle weakness, assessment of muscle strength should be considered	IIa	B	B	IVb
Comprehensive assessment of lower extremity function
For patients with anticipated frailty, assessment of Short Physical Performance Battery (SPPB) should be considered	IIa	B	B	IVa
Assessment of exercise capacity
If CPX cannot be performed, the 6-minute walk test should be considered	IIa	B	B	II
Shuttle walking test may be considered	IIb	B	C1	II
Exercise stress tests (other than CPX) may be considered	IIb	B	C1	III
Assessment of balance function
In patients with suspected frailty and risk of falling, “Single leg standing time”, “Functional reach test”, or “Timed up and go test” may be considered	IIb	B	C1	III

COR, class of recommendation; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

In CR clinical practice, it is extremely important to measure and evaluate physical function, as improvement of physical function is one of the major goals of CR; the body part to be trained and the function to be improved differ according to which specific part of the body is impaired. There are many methods to measure physical function; here we describe the more commonly used ones in the clinical practice of CR (Table 6).

Table 6. Characteristics of Various Physical Function Evaluation Methods and Indices

Evaluation methods and indices	Characteristics, benefits, and disadvantages
Classification based on physical activity capacity
NYHA functional class	Strong relationship with exercise capacity and prognosis
	Widely used in daily clinical practice; simple and highly useful
	Broad classification, and difficult to reflect detailed changes in symptoms
	Lack of objectivity
SAS (Specific Activity Scale)	Developed to complement the NYHA functional class, and quantified V̇O2 at symptom onset by MET
	Suitable for evaluation of NYHA class II
Evaluation of muscle strength and muscle mass
Measurement of knee extension muscle strength	Important to evaluate current muscle strength level because it directly affects gait and ADL
	Also useful for determining the effect of resistance training
Measurement of lower extremity muscle mass	Screening for sarcopenia and frailty is possible. There are many measurement methods such as dual-energy X-ray absorptiometry (DXA), bioimpedance analysis (BIA), MRI, and CT
	It is necessary to measure with an understanding of the characteristics of each method
	Comparison of different measurement methods is difficult
Handgrip strength	Measuring with a relatively simple device is possible
	Usefulness as a prognostic factor has been reported in large-scale clinical trials
	Also included in the diagnostic criteria for sarcopenia and frailty in Japan
Comprehensive lower extremity functional evaluation
SPPB (Short Physical Performance Battery)	Especially in older people with frailty or at risk of frailty, it can be used for comprehensive evaluation of lower limb function
	Good at predicting prognosis and ADL, such as inability to walk in the next few years, and commonly used in clinical practice
	Somewhat complicated due to measuring with different 3 methods
Walk test
Gait speed	Physiological exercise of walking, not requiring any special equipment
	In patients with CVD or older people, comfortable gait speed often used
	Also used as a criterion for sarcopenia and frailty
Balance ability (important test to assess stability)
Single leg standing time	Usually performed with the eyes open
	Used to diagnose “musculoskeletal ambulation disability symptom complex”
	Easy-to-use and highly useful
Functional reach test	Also useful as a screening tool for fall risk in older people
Timed Up & Go test	Used to evaluate “musculoskeletal ambulation disability symptom complex”, and also used to assess the risk of falling and as a simple screening for frailty
Exercise capacity evaluation
6-minute walk test	A maximal exercise stress test to measure the 6MWD
	Methods are issued in detail in the statement of American Thoracic Society
	Highly correlated with peak V̇O2 obtained from CPX, and also used to estimate prognosis
	Difficult to make interinstitutional comparisons: the results are influenced by the method used, and the results get better with each test
Shuttle walking test	A multistep incremental maximal exercise stress test as well as the six-minute walk test
	V̇O2 dynamics are the same as in the 6-minute walk test, and the reliability and reproducibility are excellent
Exercise stress test (so-called exercise stress electrocardiogram)	An exercise stress test without simultaneous expiratory gas analysis
	Used to evaluate HR and BP response by exercise, and ECG diagnosis of ischemia

6MWD, 6-minute walk distance; BP, blood pressure; CPX, cardiopulmonary exercise testing; CT, computed tomography; CVD, cardiovascular disease; HR, heart rate; MET, metabolic equivalent; MRI, magnetic resonance imaging; peak V̇O₂, peak oxygen uptake; V̇O₂, oxygen uptake.

2.1 Muscle Strength

2.1.1 Knee Extensor Strength (Lower Extremity Muscle Strength)

Lower extremity muscle strength is often assessed before the start of exercise training because it is associated with many of the walking abilities and ADL. Resistance training is recommended for all CVDs, except for contraindications, for which muscle strength evaluation is essential. The most convenient bedside muscle strength evaluation is the manual muscle test. However, there are some problems related to bias of the examiner and the quantification of muscle strength. In order to measure lower extremity muscle strength more accurately, isokinetic muscle strength measurement devices are used.

2.1.2 Grip Strength

Grip strength is relatively simple to measure. In a meta-analysis of 23,480 patients with cardiac disorders, grip strength was an independent predictor of cardiac death, all-cause death and hospital admission for HF.¹⁵ In older CVD patients or those with sarcopenia, ADL such as opening the lid of a plastic bottle may be impaired, and it is important to assess upper limb muscle strength represented by grip strength.

2.2 Short Physical Performance Battery

The SPPB¹⁶ can comprehensively assess lower extremity function in suspected frail patients, especially in older patients. It consists of a 3-item assessment: (1) “balance test” (standing with the feet together side by side, semi-tandem, and tandem positions), (2) “time to walk 4 m”, and (3) “time to rise 5 times from a chair”. Each item is rated from 0 to 4, with a maximum total score of 12. The total score is interpreted in 3-point increments: “very low motor function,” “low motor function,” “moderate motor function,” and “good motor function.” A SPPB score of ≤8 is adopted by the European Working Group as one of the diagnostic criteria for sarcopenia.¹⁷

2.3 6-Minute Walk Test

The 6-minute walk test is a simple test that measures the 6MWD with maximal effort, but not using any special equipment. The purpose of this test is to evaluate capacity of walking as far as possible in 6 min. The 6-minute walk test has gained worldwide consensus according to an ATS (American Thoracic Society) statement.¹⁸ It is known to be affected by age, sex, height, weight, etc., and the formulas for estimating the normal ranges for men and women have been reported.¹⁹ In patients with heart disease, many associations with exercise capacity or prognosis have been noted, and it is also widely used to judge the effectiveness of CR.²⁰

3. CPX (Table 7)

Table 7. Recommendations and Levels of Evidence for CPX in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform CPX in order to consider the indications for heart transplantation and other advanced therapies	I	B	B	II
In patients with dyspnea on exertion or easy fatigability as a factor exercise limitation, it is recommended to perform CPX to identify the cause	I	B	B	IVb
It is recommended to measure peak V̇O2 for assessing prognosis	I	B	B	II
It should be considered in order to create an exercise prescription	IIa	B	B	II
It should be considered to determine the HR response and an optimal program for patients with AF or pacemakers, to assess BP, arrhythmia, and physical activity during exercise, and to evaluate changes in exercise capacity and treatment	IIa	B	B	II
It is not recommended to perform this as a routine test	III (No benefit)	C	C2	VI

AF, atrial fibrillation; BP, blood pressure; COR, class of recommendation; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; GOR, grade of recommendation; HR, heart rate; LOE, level of evidence; peak V̇O₂, peak oxygen uptake.

3.1 Purpose and Significance

CPX measures V̇O₂, carbon dioxide output (V̇CO₂), respiratory rate, and tidal volume by expiratory gas analysis. This method can be used to determine the statuses of cardiac function, myocardial ischemia, peripheral circulation, skeletal muscle function, vascular endothelial cell function, anemia, and autonomic nervous system activity.¹⁴ The significance of CPX is (1) to identify the cause of dyspnea and exercise limitation during exertion, (2) to determine the indication for surgery, predict prognosis, and determine the effect of treatment, as the most reliable objective indicator of exercise capacity, and (3) to determine the exercise prescription in CR and exercise programs.

3.2 Method and Timing of Implementation

Methods of stress loading include ramp (linear incremental) loading with a bicycle ergometer or treadmill. The peak respiratory exchange ratio (RER) is an indicator of the degree of loading. It is important to have a peak RER ≥1.10 to obtain a reliable peak V̇O₂ value. In order to obtain reliable peak V̇O₂ values, it is desirable to perform this method a few days after the patient has become accustomed to low-level exercise training (e.g., bicycle ergometer loading or treadmill walking).¹

Submaximal loading is usually recommended at 4–6 days after AMI onset, and symptom-limited exercise testing at 14–21 days. CPX is performed 7–10 days after cardiac surgery, after weaning from intravenous infusion in HF, during the first week of the program after heart transplantation, and when the patient is able to walk 300–500 m continuously after the installation of a left ventricular assist system/device (LVAS/LVAD). An exercise prescription using CPX is recommended in postoperative congenital heart disease (CHD), and also in older patients with HF.¹ During the outpatient CR period, CPX is performed several times to evaluate the effects and to reset the exercise prescription.¹

3.3 How to Determine the Exercise Prescription

The V̇O₂ just before the addition of anaerobic metabolism to aerobic metabolism is called the anaerobic threshold (AT).²¹ In activities above the AT, acidosis progresses and catecholamine secretion is enhanced.²² Therefore, by knowing the AT, we can set an exercise capacity range for HF patients.¹ When prescribing aerobic exercise using CPX with ramp loading, prescribe at the work rate 1 min before the AT.¹ The exercise intensity of the high-intensity portion of high-intensity interval training (HIIT) should reach at least 80% of the maximum exercise intensity, but it is advisable to check the safety of high-intensity loading with CPX beforehand. Peak V̇O₂ is closely related to skeletal muscle function.

3.4 Significance of Key Indices During the Ramp Exercise Protocol

The normal changes in the major indices during a ramp exercise protocol are shown in Figure 2. The Japanese standard values of peak V̇O₂, AT,²³ minute ventilation vs. carbon dioxide output slope (V̇E vs. V̇CO₂ slope), and ventilatory equivalent for carbon dioxide (V̇E/V̇CO₂) minimum²⁴ using a bicycle ergometer are listed in Table 8. These are affected by age and sex. V̇E vs. V̇CO₂ slope and V̇E/V̇CO₂ are affected by the magnitude of ventilation perfusion mismatch and chemoreceptor response.²⁵ Abnormally high values are observed in HF, pulmonary thromboembolism/PH, pulmonary edema, and emphysema.

Figure 2.

Changes in each index during a ramp (linear incremental) exercise protocol. V̇O₂ increases linearly. Increasing rates of V̇CO₂ are strengthened at the AT, and V̇E at the AT and respiratory compensation (RC) point. The respiratory gas exchange ratio (R), which is the ratio of V̇CO₂ to V̇O₂, begins to increase at the AT. Near the AT, the increased rate in V̇O₂/HR decreases, and the increased rate in HR increases. V̇E/V̇O₂ has an inflection point at the AT, and V̇E/V̇CO₂ has an inflection point at the RC. AT, anaerobic threshold; HR, heart rate; V̇CO₂, carbon dioxide output; V̇E, minute ventilation; V̇E/V̇CO₂, ventilatory equivalent for carbon dioxide; V̇O₂, oxygen uptake; V̇O₂/HR, oxygen pulse.

Table 8. Standard Values of Cardiopulmonary Function Indices During Cycle Ergometer Use in Japanese Subjects

Index	Men	Women
peak V̇O2	−0.272 × age +42.29	−0.196 × age +35.38
AT	−0.100 × age +21.44	−0.069 × age +19.35
V̇E vs. V̇CO2 slope	0.080 × age +22.17	0.055 × age +24.02
Minimum value of V̇E/V̇CO2	0.118 × age +21.03	0.055 × age +25.27

AT, anaerobic threshold; peak V̇O₂, peak oxygen uptake; V̇E/V̇CO₂, ventilatory equivalent for carbon dioxide; V̇E vs. V̇CO₂ slope, minute ventilation vs. carbon dioxide output slope.

More advanced HF exhibits lower levels of peak V̇O₂ and V̇O₂/HR and also ∆V̇O₂/∆work rate (WR), and a higher level of the V̇E vs. V̇CO₂ slope. In cases of markedly blunted or decreased increases in ∆V̇O₂/∆WR²⁶ and V̇O₂/HR,²⁷ accompanied by ST-segment depression, and the WR reaches a certain level, then myocardial ischemia is the most likely cause. Thus, the severity of ischemia can be determined by the degree of change.²⁶ The peak V̇O₂ of HF patients can be improved by 8–16% through aerobic exercise performed 3–5 times each week for 40–50 min each time for 3 months.^28,29 It is reported that the degree of improvement is greater in patients with a lower body mass index (BMI).²⁸ However, it is also reported that frail patients do not show significant improvement.³⁰

A phenomenon in which V̇E fluctuates >15% of the basal value in a cycle of ≈80 seconds during exercise, is called “exercise oscillatory ventilation” (EOV). EOV is an indicator of advanced HF because it is caused by delayed circulation time, hyperchemosensitivity, and decreased PaCO₂.³¹ EOV is improved by CR.³²

3.5 Assessment of Exercise Capacity

The most objective indicator of exercise capacity is peak V̇O₂.³³ The AT is approximately 50–55% of peak V̇O₂; because compensatory hyperventilation does not occur below this level,³⁴ it is an indicator of the level of daily activity. Because the standard values of peak V̇O₂ differ according to age and sex, it is difficult to assess the severity of disease based on absolute values of peak V̇O₂. It is recommended to classify deterioration of exercise capacity and HF severity based on 80%, 60%, and 40% of the standard values of peak V̇O₂ and the AT, respectively (Table 9).³⁵ When evaluating peak V̇O₂ divided by body weight, it is important to note that it may be underestimated in overweight individuals and overestimated in extremely thin individuals.

Table 9. Classification of Severity of HF by Peak V̇O₂

Predicted rate of peak V̇O2 relative to age-specific reference values	Severity of heart failure
≥80% of standard value	Normal
60–80% of standard value	Mild
40–60% of standard value	Moderate
Unable to perform the test, or <40% of the standard value	Severe

HF, heart failure; peak V̇O₂, peak oxygen uptake. (Source: based on Japan Intractable Diseases Information Center.³⁵)

3.6 Prognosis

The peak V̇O₂ is the most powerful prognostic indicator when sufficient load can be applied.^33,36,37 The extent to which peak V̇O₂ improves after CR is useful for prognosis prediction.³⁸ In recent years, the prognosis of HF has greatly improved due to therapeutic advances, and the prognosis of patients with the same peak V̇O₂ has improved.³⁹ The cardiovascular risk at 15 mL/min/kg before the year 2000 has now, after 2006, become the risk at 14 mL/min/kg. The AT is also a prognosis prediction factor.⁴⁰ V̇E vs. V̇CO₂ slope is also a well-established prognosis prediction indicator, with >34 or >35 being considered as a poor prognosis.^41,42 The MECKI score, which predicts the incidence of LVAS insertion within 2 years in HF and HF death, incorporates peak V̇O₂ and the V̇E vs. V̇CO₂ slope.⁴³ A prognostic method that combines peak V̇O₂, the V̇E vs. CO₂ slope and EOV has also been proposed.⁴⁴

4. Sarcopenia, Frailty, and Cachexia (Table 10)

Table 10. Recommendations and Levels of Evidence for the Assessment of Sarcopenia and Frailty in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Patients with suspected sarcopenia or frailty should be considered for assessment	IIa	B	B	IVa

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

Sarcopenia and frailty are relatively new concepts, and unified definition or diagnostic criteria have not yet been established. For cachexia, though the pathogenesis has been known for a long time, elucidation of the specific details of the pathogenesis and the quest for a treatment are issues that need to be addressed in the future.

4.1 Sarcopenia

The term “sarcopenia” has been translated as “age-related loss of muscle mass” or “age-related muscle weakness”. Sarcopenia is a concept of a condition in which skeletal muscle mass decreases due to a decrease in physical activity associated with aging, poor nutrition (low calorie, low protein intake), and various diseases, resulting in a decline in overall muscle mass and physical function.

The 2010 European Sarcopenia Working Group classified sarcopenia as “primary sarcopenia,” which has no factors other than aging, and “secondary sarcopenia,” which has factors such as disuse, inflammation, underlying disease, and poor nutrition.^17,45 Especially in HF, skeletal muscle tends to decrease due to the pathological condition, and skeletal muscle mass is reported to be associated with exercise capacity,⁴⁶ and prognosis.⁴⁷ However, the prevalence of sarcopenia in HF patients is not clear.

Criteria combining skeletal muscle mass and function (muscle strength, gait speed, etc.) have been devised to assess sarcopenia. In Japan, the diagnostic criteria proposed by the Asian Working Group for Sarcopenia are often used (Table 11).⁴⁸

Table 11. Diagnostic Criteria for Sarcopenia of the Asian Working Group for Sarcopenia

1. Muscle mass

Mass of skeletal muscle index (skeleton appendicular muscle mass/height2, kg/m2)

Dual energy X-ray absorptiometry (DXA)

Men: <7.0 kg/m2, Women: <5.4 kg/m2

Bioelectrical impedance analysis (BIA)

Men: <7.0 kg/m2, Women: <5.7 kg/m2

2. Muscle strength

Grip strength: Men: <28 kg, Women: <18 kg

3. Physical function

Gait speed: <1.0 m/s

(Source: based on Chen LK, et al, 2020.⁴⁸)

4.2 Frailty

Among the diagnostic criteria for frailty proposed to date,⁴⁹ the criterion of Fried et al (phenotype model) is the most commonly used in many academic studies.⁵⁰ This criterion, proposed by the Cardiovascular Health Study (CHS), is determined by the following 5 items that emerge together with the manifestation of frailty: weight loss, muscle weakness, decreased gait speed, poor endurance or exhaustion, and low activity (Table 12).^50–53 In a meta-analysis in the Netherlands, the prevalence of frailty in community-dwelling older people based on the CHS criteria was 9.9% (95% confidence interval (CI) 9.6 to 10.2),⁵⁴ and in Japan it was reported to be 7.4% (95% CI 6.1 to 9.0).⁵⁵ A meta-analysis of HF patients in Oregon, USA, reported a high prevalence of frailty based on the CHS criteria, with a prevalence of 43% (95% CI 34 to 52).⁵⁶ However, most of the original papers cited in that meta-analysis did not specify “inability to walk” as an exclusion criterion, and did not take into account the point of “not a disability, but reversible with appropriate intervention”.⁴⁹ In other words, the complication rate of frailty in HF is likely to be overestimated.

Table 12. Diagnostic Criteria for Frailty by the Cardiovascular Health Study

• Weight loss: Unintentional annual weight loss of ≥5%, etc.

• Decrease in grip strength (weakness): men <26 kg, women <18 kg, etc.

• Becomes tired easily (poor endurance or exhaustion): feeling tired, unusual weakness, etc.

• Decreased gait speed (slowness): <0.8 m/s, etc.

• Decrease in physical activity (low activity): men <383 kcal/week, women <270 kcal/week, etc.

*If ≥3 items apply, the patient is considered to be frail. If only 1 or 2 items apply, the patient is diagnosed as pre-frailty

(Source: based on Fried LP, et al, 2001⁵⁰, Walston J, et al, 2006⁵¹, Xue QL, et al, 2008⁵², Singh M, et al, 2014.⁵³)

It is necessary to understand frailty as a syndrome that includes undernutrition, mental and cognitive decline, and comorbidities, in addition to the decline in physical function, and to apply exercise training, which is expected to be an effective treatment, and to practice innovative comprehensive CR, such as combining it with new treatment strategies.⁵⁷

4.3 Cachexia

Cachexia is a pathological status caused by nutritional disorder, inflammation or oxidative stress, hypogonadism, anemia, insulin resistance, and enhanced protein catabolism associated with chronic diseases including malignancy, chronic HF, and chronic respiratory failure; in addition to skeletal muscle loss, a metabolic abnormality characterized by adipose tissue loss is included. This is a syndrome marked by weight loss, muscle weakness, and decreased capacity for physical activity.⁵⁸ In 2006, the Cachexia Consensus Working Group proposed a definition that combines weight loss with clinical findings.⁵⁸ Although cachexia is a strong poor prognostic factor in HF,⁵⁹ it is distinguished from sarcopenia, which is mainly characterized by skeletal muscle mass loss, by the fact that adipose tissue is also reduced in addition to skeletal muscle mass.⁵⁸ Nutritional disorder is a characteristic finding of cachexia, and its possible causes include anorexia, polypharmacy, digestive and absorptive deficiencies associated with intestinal edema, physical inactivity, and increased resting energy demand.⁶⁰ In addition, it has been suggested that in patients with HF, intestinal edema from congestion, and ischemia due to circulatory failure, can increase intestinal mucosal permeability; endotoxins and bacteria from among the Gram-negative rods in the intestine can enter the bloodstream, increasing inflammatory cytokines and enhancing catabolism.^61–64

III. General Principles of Exercise Prescription

1. Exercise Prescription (Table 13)

Table 13. Recommendations and Levels of Evidence for Aerobic Exercise Training and Resistance Training in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform moderate-intensity endurance training	I	A	A	I
In patients with muscle weakness and frailty, it is recommended to perform resistance training from a low intensity	I	A	B	I
In addition to endurance training, resistance training should be considered	IIa	B	B	II
During the initial phase of the exercise program, or for patients with reduced exercise capacity, low-intensity endurance training may be considered	IIb	B	B	II
Relatively high-intensity endurance training may be considered in the late recovery period or maintenance period when the disease has stabilized	IIb	B	B	II
High-intensity interval training may be considered for low-risk, stable patients	IIb	C	B	I

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

1.1 Concept of Exercise Prescription

A safe and effective exercise training program designed to meet the individual’s health status and physical function is termed an “exercise prescription”.⁶⁵ Exercise programs in cardiac rehabilitation (CR) focus on aerobic exercise, resistance training, and stretching.⁶⁶

1.2 Components of the Exercise Training Session

Each exercise session consists of a 5–10-min warm-up, the main exercise prescribed in its duration (aerobic or resistance training), and a 5–10-min cool-down. The warm-up and cool-down consist of stretching and aerobic exercise of lower intensity than the main exercise. As for the main exercise, aerobic exercise and resistance training are generally performed on separate days, but they may be performed on the same day if tolerated.

2. Types of Exercise

2.1 Aerobic Exercise

Aerobic exercise is based on rhythmic motion of large muscle groups (pectoralis major, latissimus dorsi, quadriceps femoris, rectus abdominis, gluteus maximus, and erector spinae) for a certain period of time. The exercise prescription is based on FITT-VP: frequency, intensity, time, type, volume, and progression/revision⁶⁶ (Table 14).

Table 14. FITT-VP Principles of Exercise Prescription

F	Frequency: how often
I	Intensity: how hard
T	Time: duration or how long
T	Type: mode or what kind of exercise
V	Volume: amount
P	Progression/revision

2.1.1 Frequency

The frequency of aerobic exercise is determined according to exercise capacity, exercise intensity, target health status and physical function. High-intensity exercise is performed at least 3 times per week, a combination of moderate- to high-intensity exercise 3–5 times per week, and low- to moderate-intensity exercise at least 5 times per week. Although exercising once or twice per week has been shown to be beneficial to health and physical function if a high level of physical activity is maintained, engaging in an unfamiliar exercise only once or twice per week is not recommended because it increases the risk of injury. In addition to participation in supervised exercise training, outpatients should be instructed in unsupervised voluntary training, and maintaining the frequency of exercise.

2.1.2 Intensity of Exercise

Exercise of <3.0 metabolic equivalents (METs) is generally described as “low-intensity”, 3.0 to <6.0 METs as “moderate-intensity”, and >6.0 METs as “high-intensity”, but these general values are not used in exercise training for patients with cardiovascular disease (CVD). As for the methods used for determining exercise prescription based on exercise stress tests, there are exercise prescriptions based on the anaerobic threshold (AT), heart rate reserve (HRR), and rating of perceived exertion (RPE) (Table 15). Using a resting HR of +30 (20) beats/min is not a recommended method and should only be used for convenience in patients who have not yet undergone an exercise stress test until an exercise prescription is determined based on the exercise stress test.⁶⁷ For patients with chronotropic incompetence, such as those with pacemaker implantation or those receiving β-blockers, and for those with arrhythmias such as atrial fibrillation (AF), cardiopulmonary exercise testing (CPX) is used to directly measure energy metabolism and ventilatory response during exercise; the exercise prescription is made at the AT level, or relative intensity (% maximal V̇O₂, % peak V̇O₂) to maximal V̇O₂ or peak V̇O₂ is used.⁶⁶ The AT can be also assessed from submaximal exercise testing, so it can be determined even in critically ill patients. Exercise intensity at less than the AT is very safe because it is unlikely to cause acidosis or a marked increase in blood levels of catecholamines. When exercise stress testing is not possible due to the patient’s condition or a poorly equipped facility, training intensity should be determined by one of the methods listed in Table 16. If the RPE is used as an evaluation index, the Borg scale is used (Figure 3).⁶⁸ Talk Test is one of the simple methods for estimating exercise intensity.⁶⁹

Table 15. How to Determine Exercise Intensity for Patients With AMI After the Recovery Phase

A. 40–60% of HRR (= maximum HR − resting HR)

Karvonen formula: [maximum HR − resting HR] × k + resting HR

k: 0.6 for normal patients (e.g., young patients with uncomplicated AMI)

0.4–0.5 for high-risk patients, and 0.3–0.5 for heart failure patients

B. HR at the AT level or 40–60% of peak V̇O2

C. RPE: “Somewhat hard” or just below (Borg scale: 12–13)

D. Simplified method: resting HR + 30/min (patients receiving beta-blockers: resting HR + 20/min)

Note that exercise intensity should be low in high-risk patients [(1) left ventricular dysfunction (LVEF <40%), (2) prolonged occlusion of the left anterior descending artery (patients who failed reperfusion therapy), (3) patients with severe 3-vessel disease, (4) older patients (≥70 years)]

AMI, acute myocardial infarction; AT, anaerobic threshold; HR, heart rate; HRR, heart rate reserve; LVEF, left ventricular ejection fraction; peak V̇O₂, peak oxygen uptake; RPE, rating of perceived exertion.

Table 16. How to Determine Exercise Intensity When Exercise Stress Test Cannot Be Conducted

	Simple HR prescription	RPE	Talk Test
Method	Intensity of resting HR + 30/min (20/min in patients receiving beta blockers)	Borg scale 12–13 Borg scale 11–13 for heart failure patients	Exercise intensity that can be done while talking comfortably
Points to note	The maximum allowable range is 120/min or less	Need to be interviewed frequently during exercise
Not applicable	Patients with chronotropic incompetence, AF, pacemaker implantation	Patients with few symptoms, such as silent myocardial ischemia, and patients with communication problems such as dementia

Note: See text for simplified HR prescription. AF, atrial fibrillation; HR, heart rate; RPE, rating of perceived exertion.

Figure 3.

Borg scale and exercise intensity. Either RPE or exercise intensity (%) is used. RPE, rating of perceived exertion. (Source: based on Borg, 1974.⁶⁸)

2.1.3 Time (Duration)

The duration of exercise should be at least 10 min per session, but for patients with severely impaired exercise capacity it should begin with less than 10 min and gradually increase by 1–5 min per session.⁷⁰ The final goal is 20–60 min.

2.1.4 Type (Mode or What Kind)

Continuation of exercise training is important, so the choice of exercise that the patient is able to continue comfortably for a long time is important. In general, walking is the easiest exercise to perform and its intensity can be easily adjusted. Other forms of exercise, such as cycling, dancing, and water exercise, can provide similar aerobic benefits, so the type of exercise is determined in consideration of comorbidities and patient preference. Combining multiple types of exercise, such as walking and cycling (cross-training), can help reduce the burden on a single joint or bone and may also improve general endurance.⁶⁶

2.1.5 Exercise Volume (Amount)

Exercise volume is the product of frequency, intensity, and duration of exercise. If a person is prescribed 30 min of exercise per session, he or she should be instructed to perform 30 min of exercise in 1 session, or 10 min of exercise 3 times in 1 session. The “Physical Activity Reference for Health Promotion 2013”⁷¹ recommends 8,000 to 10,000 steps/day or 23 exercises per week (exercise = MET × time) as the target amount of exercise for healthy adults.

2.1.6 Progression/Revision

In order to maintain exercise adherence and prevent complications such as exercise-related injuries, start with low-intensity and short-duration exercise, then gradually increase the intensity and duration.⁶⁶ Especially in frail patients and patients with greater physical deconditioning, it is important to start with low-intensity exercise of less than 10 min per session and gradually increase the intensity by 1–5 min per session to reach the goal.^72–75 The target training content should be set according to the activity level before the onset of disease, type of employment, hobbies, living environment, and the patient’s wishes. In patients with heart failure (HF), it is necessary to periodically review (revise) the exercise prescription appropriately; sometimes the intensity and duration of exercise need to be reduced according to changes in the disease state.

2.2 Resistance Training

In addition to improving muscular strength and endurance, resistance training during the recovery phase is prescribed to increase lean body mass, improve insulin sensitivity, prevent falls, improve self-efficacy, and prevent and manage chronic diseases such as low back pain and obesity.⁷⁶ Exercise prescription for resistance training is mainly done in Phase II (recovery phase), especially for the upper extremities, starting 10–12 weeks after midline incision.⁶⁵ Absolute contraindications to this training include: (1) unstable angina, (2) uncompensated HF, (3) uncontrolled arrhythmia, (4) severe pulmonary hypertension (PH: mean pulmonary artery pressure >55 mmHg), (5) severe and symptomatic aortic valve stenosis, (6) acute myocarditis, endocarditis, epicarditis, (7) uncontrolled hypertension (>180/110 mmHg), and (8) acute aortic dissection. The relative contraindications that should be discussed with a physician before training include: (1) major risk factors for coronary artery disease (CAD), (2) diabetes mellitus, and (3) uncontrolled hypertension (>160/100 mmHg).⁷⁶ Resistance training should be prescribed separate from rhythmic low-intensity resistance exercise using rubber bands/balls at the bedside in the acute phase, or squats and calf raises at the bedside. Exercise prescription for resistance training is based on FITT (i.e., frequency, intensity, time, and type), as in the case of aerobic exercise prescription.^65,66,76

2.2.1 Frequency

Ideally, the frequency should be with an interval of about 2 days between, 2–3 times per week.^76,77

2.2.2 Intensity of Exercise

For the intensity of the exercise, measure the 1-repetition maximum (1RM) and prescribe using 40–60% of 1RM (%1RM method). In addition to this method, there are others such as the progression method, in which the weight is gradually increased from a moderate weight, and the estimated %1RM method, in which a certain intensity is determined and the approximate load is determined by the number of repetitions (as a guide, if 5 repetitions are possible, 90% of 1RM, if 8 repetitions, 80% of 1RM, if 12 repetitions, 70% of 1RM, etc.),⁷⁶ and also the Borg scale can be used.

At the time of exercise initiation, it is recommended to start with an intensity of 10–15 repetitions without significant fatigue, of rating of perceived exertion (RPE) 11–13,⁷⁶ or to start with preliminary training with an intensity of 30% 1RM or RPE <12.⁷⁸

2.2.3 Time (Duration or How Long)

It is recommended to prescribe 1–3 sets of 8–10 different types of exercises, mainly for the large muscle group, for 30–45 min. A 90-s recovery period between sets avoids a cumulative increase in blood pressure.⁷⁹

2.2.4 Type (Mode or What Kind)

In addition to dumbbells and iron arrays, pneumatic and hydraulic resistance, rubber bands, and body weight can also be used. A well-balanced training of large muscle groups should be prescribed,^65,66,76 and older patients who have difficulty using a machine can be instructed to exercise with a rubber band.

2.2.5 Other Methods

In recent years, a training method in which the base of the extremity is moderately pressurized with a special pressure belt and blood flow is restricted has been used (KAATSU training); doing this for a short period of time and with a low-intensity load (20–30% of 1RM) has been attracting attention, but clinical studies in patients with cardiac disease are still limited.^80,81

2.3 High-Intensity Interval Training

In recent years, increasing evidence has shown the feasibility and short-term effectiveness of HIIT, which involves alternating high- and moderate-intensity exercise.^82–86 Table 17 shows examples of common protocols. In many cases, it is difficult to continue 3–4 min of high-intensity exercise (85–95% HRmax) from the beginning, so it is desirable to prepare individual protocols, such as starting with 70% HRmax intensity at the beginning of training.⁸⁷ In patients with stable symptoms and no problems with conventional aerobic training, it is recommended to prescribe HIIT that takes into account the patient’s wishes, exercise capacity, severity of underlying disease, and comorbidities.^65,88 The long-term effects of HIIT have not yet been established, and further studies are needed.

Table 17. Example of General Protocol for HIIT

Training frequency	3 times per week
Warming up	Intensity: 60% of maximum HR, or 20–30% or maximum load (work rate)
	Time: 5–10 min
Exercise intensity	High intensity: 85–95% of maximum HR
	Medium intensity: 60–70% of maximum HR
Interval	3–4 min of high-intensity exercise × 4 times
	3–4 min of moderate-intensity exercise × 3 times
Cool down	Intensity: 50% of the maximum HR or 20% of the maximum load (work rate)
	Time: 5 min
Duration	40–50 min
Type of exercise	Bicycle ergometer, treadmill

HIIT, high intensity interval training; HR, heart rate.

2.4 Respiratory Muscle Training

In patients with chronic HF, respiratory muscle strength is decreased, which is associated with HF severity, exercise capacity, and prognosis.^89–91 In addition, inspiratory muscle training for chronic HF improves inspiratory muscle strength, exercise capacity, and quality of life (QOL).⁹² It is particularly effective in patients with decreased inspiratory muscle strength.⁹³ In the field of cardiovascular surgery, it has been reported to be effective mainly in post-CABG patients. A meta-analysis reported that preoperative training improved inspiratory muscle strength, vital capacity, and expiratory volume in 1 second, and contributed to a reduced risk of postoperative pulmonary complications and a shorter postoperative hospital stay.⁹⁴ However, the relationship of such training and exercise capacity or prognosis is unclear, and further evidence needs to be collected.

2.5 Neuromuscular Electrical Stimulation

Neuromuscular electrical stimulation (NMES) is a physical therapy that stimulates muscle contraction by percutaneously applying electrical current to the nerves. Although a meta-analysis of chronic HF patients has shown that NMES improved exercise capacity,⁹⁵ it was inferior to aerobic exercise in improving peak V̇O₂.⁹⁵ Therefore, NMES is positioned as an alternative therapy for patients who are unable to do voluntary exercise sufficiently.

3. Exercise Training in Practice

In Japan, the standard CR program after hospital discharge is a combination of supervised outpatient CR (known as center-based CR or hospital-based CR) and home-based exercise training. The outpatient CR period is the recovery period from hospital discharge to the end of the insurance coverage period (150 days). The first half of this period will be aimed at recovery of physical function and lifestyle management under the supervision and counseling of multidisciplinary team, and the second half will be a transition period aiming at independence. The usefulness of center-based CR has been widely reported in patients after myocardial infarction (MI), after CABG surgery,^96,97 and in chronic heart failure.^98,99 In patients with CAD, there is a report that the more outpatient CR a patient participates in, the lower the risk of total mortality and MI over the subsequent 4 years.¹⁰⁰

3.1 Exercise Type, Time, Intensity, and Frequency

The exercise modalities in outpatient CR are influenced by the size of the facility, but facilities should prepare the equipment to perform many modalities of exercise, such as aerobic exercise (including bicycle ergometers, treadmills, track walking, and aerobic exercises) and resistance training (including weight-bearing, rubber bands, dumbbells, and strength training machines); these methods are combined based on the patient’s risk, comorbidities, and wishes. Aerobic exercise is the mainstay, but in cases of significant muscle weakness, sufficient time should be spent on low-intensity resistance training.

The duration of exercise should be gradually increased according to the patient’s condition, with a daily target of 60 min, which is the upper limit, and the standard duration is 180 min/week. The intensity of exercise is recommended to set based on the HR response and the AT by CPX before and after hospital discharge. The frequency of exercise should be set at the number of times in the exercise prescription (e.g., 5 times/week) in combination with supervised outpatient CR and home-based exercise training. The frequency of outpatient CR is affected by the patient’s motivation, employment/family support, financial status, and access, but it is desirable for patients to participate in outpatient CR 2–3 times each week if possible, or at least once a week.

3.2 Supporting Changes During the Program

a. Support for Changes in Response During Exercise

In outpatient CR, if the Borg scale or HR decreases with the same aerobic exercise, it is considered to be an improvement in exercise capacity, and increasing the volume of exercise (mainly intensity and duration) should be considered. On the other hand, if the Borg scale or HR increases, it is considered to be a deterioration of exercise capacity. Whether the cause is insufficient total physical activity, or worsening chronic HF or myocardial ischemia, the countermeasures to be taken are completely different. Therefore, careful judgment should be made by referring to several indices, such as body weight, edema, resting HR, blood concentration of BNP, oxygen saturation during exercise, and ECG. If it is the former cause, ask whether there are any changes in physical activity in the home exercise environment, type, or time of day as a measure to increase the amount of home exercise (mainly frequency and duration); if the latter cause, take measures according to the medical condition (see “ IV.3.2 Chronic Heart Failure ”).

b. Adjustment of Exercise Prescription

At the time of discharge from the acute care hospital or introduction to the late recovery phase, an exercise stress test should be performed to evaluate the presence of myocardial ischemia, exercise capacity, and the safety zone of exercise training to determine the exercise prescription. The recommended moderate-intensity exercise intensity to be prescribed for patients with CVD is 40–60% of peak V̇O₂ and 40–60% of HRR (k=0.4–0.6 in the Karvonen formula). In Japan, exercise prescription of the AT with CPX is widely used, and in this case, it corresponds to ≈40–60% of peak V̇O₂. The advantage is that AT prescription can also be obtained from maximal stress testing.

In the early recovery phase, if the patient has a good understanding of CR and is judged to have a wide safety margin for exercise, the exercise stress test can be omitted and the exercise prescription is adjusted based on the HR and blood pressure responses during exercise and the RPE. At the time of transition to the maintenance phase, CPX is recommended for the purpose of exercise capacity evaluation and re-prescription.

The resting HR may gradually decrease during the program due to stabilization of the disease or the effect of β-blockers. In such a case, the intensity and duration of exercise required to reach a certain target HR gradually increase, but at the same time, if the exercise capacity is sufficiently improved by the rehabilitation effect, the program can be continued without difficulty. If it becomes practically difficult to reach the target HR, or as a result of such a gradual increase in exercise volume in chronic HF there is an increase in BNP concentration, probably caused by overload, necessary tests should be performed and the prescription should be revised. At the end of the CR program, CPX should be performed again, and the exercise prescription would be reviewed based on the results and progress during the program period to determine the final exercise prescription.

4. Target Diseases, Indications and Contraindications

4.1 Target Diseases and Indications in CR

In Japan, the target diseases in CR covered by insurance are AMI, angina pectoris, after implantation of arrhythmia devices and assistive devices, HF in general including PH, after heart transplantation, after cardiac surgery including transcatheter aortic valve implantation, after stent graft intervention including great vessel disease, and peripheral vascular diseases that cause intermittent claudication.¹⁰¹

4.2 Contraindications in Exercise Stress Test and Exercise Training

When conducting an exercise stress test, contraindications should be considered when there is a high risk that exercise stress will rapidly worsen the condition, such as severe AMI or unstable valvular disease. Contraindications to exercise testing are listed in Table 18.^66,102,103 In the case of relative contraindications, the stress test should be performed when the benefit outweighs the risk.

Table 18. Contraindications of Diseases and Conditions for Exercise Stress Test

Absolute contraindications

1. AMI developed within 2 days

2. Unstable angina not controlled with medical treatment

3. Uncontrolled arrhythmia that causes symptoms or hemodynamic compromise

4. Symptomatic severe aortic stenosis

5. Uncontrolled symptomatic heart failure

6. Acute pulmonary embolism or pulmonary infarction

7. Acute myocarditis or pericarditis

8. Acute aortic dissection

9. Mental disorders associated with communication difficulties

Relative contraindications

1. Left main coronary artery stenosis

2. Moderate stenotic valvular heart disease

3. Electrolyte abnormality

4. Severe hypertension*

5. Tachyarrhythmia or bradyarrhythmia

6. Hypertrophic cardiomyopathy or other outflow tract obstruction

7. Mental or physical impairment leading to inability to exercise adequately

8. Advanced atrioventricular block

*It is recommended that severe hypertension is considered as systolic blood pressure >200 mmHg and/or a diastolic blood pressure >110 mmHg, in principle. AMI, acute myocardial infarction.

Absolute and relative contraindications to aggressive exercise training are listed in Table 19.^66,102,103 Even advanced HF of NYHA classification IV, which is not indicated for systemic exercise training, is an indication for low-intensity physical therapy and exercise training if the patient is stable with no ongoing deterioration. Exercise training is indicated in stable patients, even with severe CAD, who do not have a tendency to deteriorate rapidly. Even if exercise load is contraindicated at some point, it may be indicated later as the condition changes, so re-evaluation should be performed.

Table 19. Contraindications for Aggressive Exercise Training

Absolute contraindications

1. Unstable angina or low-threshold myocardial ischemia induced by slow walking (2 METs) on a flat surface

2. Exacerbation of perceived heart failure symptoms of (e.g., dyspnea, easy fatigability) during the recent 3 days

3. Uncontrolled arrhythmias causing hemodynamic abnormalities (ventricular fibrillation, sustained ventricular tachycardia)

4. Severe valvular disease indicated for surgery, especially symptomatic aortic stenosis

5. Severe left ventricular outflow tract stenosis due to obstructive hypertrophic cardiomyopathy, etc.

6. Acute pulmonary embolism, pulmonary infarction and deep vein thrombosis

7. Active myocarditis, pericarditis, endocarditis

8. Acute systemic disease or fever

9. Other diseases in which exercise training is contraindicated (acute aortic dissection, moderate or severe aortic aneurysm, severe hypertension,*1 thrombophlebitis, embolism within 2 weeks, and serious organ diseases, etc.)

10. Mental or physical impairment that interferes with safe implementation of exercise training

Relative contraindications

1. AMI within 2 days of onset with high risk of serious complications*2

2. Left main coronary artery stenosis

3. Asymptomatic severe aortic stenosis

4. Advanced atrioventricular block

5. Tachyarrhythmias or bradyarrhythmias with poorly controlled HR that are hemodynamically preserved (e.g., nonsustained ventricular tachycardia, tachyarrhythmia with AF, tachyarrhythmia with atrial flutter, etc.)

6. Recent stroke*3

7. Mental or physical impairment leading to inability to exercise adequately

8. Systemic diseases that have not been corrected*4

Not contraindicated

1. Older patients

2. Decreased LVEF

3. Arrhythmia with hemodynamically preserved and well-controlled HR (e.g., AF, atrial flutter)

4. Hemodynamically stable patients on intravenous inotropic drugs

5. Placement of LVAD, cardiac implantable device (e.g., permanent pacemaker, ICD, CRT-D)

*¹As a general rule, defined as systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg, or both. *²Transmural extensive anterior infarction, prolonged ST-segment elevation, etc. *³Includes transient ischemic attack. *⁴Anemia, electrolyte abnormality, thyroid disorder, etc. AF, atrial fibrillation; AMI, acute myocardial infarction; CRT-D, cardiac resynchronization therapy defibrillator; HR, heart rate; ICD, implantable cardioverter defibrillator; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; MET, metabolic equivalent. (Source: based on JCS 2017 guideline,¹⁰² Fletcher GF, et al, 2013,⁶⁶ JCS 2018 guideline.¹⁰³)

5. Termination Criteria for and Risk of Exercise Training, and Accident Prevention

5.1 Criteria for Terminating Exercise Training

The criteria for terminating exercise should be based on both patient-perceived factors and objective factors assessed by medical professionals, such as cardiologists and CR instructors.¹⁰⁴ The criteria for terminating exercise should be divided into absolute and relative criteria based on the patient’s condition, comorbidities, and medications (Table 20). If a patient wishes to stop during exercising, it is an absolute criterion to terminate exercise immediately, regardless of the reason. Exercise should be stopped immediately, not only when the patient is unaware of dangerous symptoms during exercise, such as when the patient does not respond sufficiently to a call during exercise, but also when the medical staff cannot objectively detect a dangerous situation for any reason, such as when ECG electrodes are removed. Exercise should be discontinued immediately when ≥2 of the objective termination criteria occur simultaneously. If chest symptoms (chest pain, shortness of breath, palpitations) or other perceived symptoms (hypoglycemic attack, arrhythmia, dizziness, headache, leg pain, severe fatigue, mood disorder, arthralgia, muscle pain, etc.) worsen at the same exercise intensity, and if these perceived symptoms continue to worsen even when the exercise intensity is reduced, the exercise should be terminated.

Table 20. Criteria for Terminating Exercise Training

Absolute termination criteria

• Patient’s wish to terminate exercise

• Patient is expected to be unable to detect dangerous symptoms during exercise, or patient has deteriorating consciousness

• Incidence of cardiac arrest, severe bradycardia, fatal arrhythmia (ventricular tachycardia, ventricular fibrillation), or when these cannot be ruled out

• Sudden deterioration of vital signs or appearance of perceived symptoms (severe chest, abdominal/back pain, epileptic seizure, loss of consciousness, hypotension, severe joint/muscle pain, etc.)

• On ECG, ST-segment elevation ≥1 mm in the induction without Q wave (other than aVR, aVR, V1 induction)

• Accidents (falls, trauma, equipment failure, etc.)

Relative termination criteria

• Worsening of perceived chest symptoms or other symptoms (e.g., hypoglycemic attack, arrhythmia, dizziness, headache, leg pain, severe fatigue, poor mood, joint or muscle pain) at the same intensity or with a decrease in exercise intensity

• Transcutaneous arterial oxygen saturation drops to less than 90%, or decrease of 5% or more from rest

• New arrhythmia or ST-segment depression ≥1 mm on ECG

• Blood pressure decreased (systolic pressure <80 mmHg) or increased (systolic pressure ≥250 mmHg, diastolic pressure ≥115 mmHg)

• Appearance of bradycardia (HR ≤40/min)

• If the patient is judged to be unable to follow instructions during exercise, or it is difficult to continue exercise training due to the risk of falling

HR, heart rate.

5.2 Risk of Exercise Training

Regarding the safety reports of CR, events (AMI, cardiac arrest, or death) did not occur in 277,721 patient-hours in exercise training based on the CR program recommended by the Japanese Association of CR, and there was no difference in events between the exercise training group and the non-exercise group for HF.^105,106 Therefore, it is considered that supervised exercise training can be safely performed with exercise prescriptions based on the exercise stress tests. However, patients with CAD who have residual ischemia are at high risk of developing acute coronary syndrome (ACS) or fatal arrhythmias during exercise, so caution is required (Table 20). For further information on the risks of exercise training and the evaluation for each CVD, please refer to the individual sections (Chapters IV and V).

The general risks of exercise training are falls and fractures. In particular, older and obese patients, who often have orthopedic diseases of the lumbar spine and lower limb joints, should be aware of the risk of exacerbation by exercise. There is a risk of venous thromboembolism in patients who have been bedridden for more than 3 days, have undergone major surgery within 4 weeks, have been confined to a wheelchair for a long period of time, are obese, or have cancer and are not anticoagulated. Patients with diabetic complications should be carefully evaluated for the various risks of complications. Patients with peripheral neuropathy may be at risk for worsening foot lesions with exercise training, thus it is important to refrain from load exercise and to provide adequate foot care.

5.3 Accident Prevention

From the viewpoint of preventing accidents during exercise, not only patients who are contraindicated for exercise training, but also those who are judged not to be given exercise training due to their physical condition on that day, should not perform such exercises. In patients with CVD, 72% of complications during exercise training have been reported to occur during warm-up and cool-down.¹⁰⁷ To prevent accidents during exercise training, sufficient attention should be paid not only during exercise but also after exercise. At the beginning of exercise, start with preparatory exercises such as stretching, and perform a thorough warm-up. At the end of exercise, cool down by running/walking at a reduced intensity and speed, or by performing consolidation exercises such as stretching, and gradually return to resting blood pressure and HR to prevent hypotension and dizziness after exercise. To date, there are few reports on the prevention of accidents during exercise. As a reference for general information, the “Guidelines for safety management and promotion in rehabilitation medicine, 2nd edition”¹⁰⁸ by the Japanese Association of Rehabilitation Medicine, may be used, but care should be taken because it does not describe the prevention of accidents during exercise in CR.

In exercise training, it is important to extract and share information about possible cardiovascular events and any complications that may occur in each patient as taken from the standpoint of each team member as an expert. It is important to explain these risks to patients in advance and to take measures to minimize the risks, while always being prepared for the unexpected.

IV. CR by Disease

1. AMI, ACS (Table 21)

Table 21. Recommendations and Levels of Evidence for CR in Patients With ACS

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to continue the recovery phase of CR to improve exercise capacity, QOL, and prognosis	I	A	A	I
It is recommended to perform acute-phase CR using a clinical pathway in the acute phase	I	A	B	II
It is recommended to perform exercise stress test assessment before or early after hospital discharge to evaluate the prognosis, physical activity, and necessity of additional treatment	I	A	B	II
It is recommended that the attending physician actively encourage CR to increase the adoption rate of outpatient CR	I	A	A	I
It is recommended that a combined program of supervised outpatient CR with home-based exercise training is provided for intermediate and high-risk patients, if in stable condition	I	A	A	I
Risk of post-AMI should be considered, and early discharge should be considered in patients with low risk	IIa	A	B	II
For patients who have achieved early reperfusion and have no obvious complications, CR should be considered in the early acute phase in the CCU for early ambulation	IIa	B	B	II
For exercise training, combining with resistance training should be considered	IIa	B	B	II

ACS, acute coronary syndrome; AMI, acute myocardial infarction; CCU, coronary care unit; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; QOL, quality of life.

1.1 Purpose

Acute coronary syndrome (ACS) is classified into ST elevation myocardial infarction (STEMI), non-STEMI, and unstable angina.¹⁰⁹ The purpose of CR for ACS is to safely achieve activities of daily living (ADL) and improve prognosis after hospital discharge by comprehensive intervention for patients early in their hospitalization.

1.2 Phase-Based Classification

In Japan, in-hospital deaths from acute myocardial infarction (AMI) remains high at ≈8%, cardiovascular events occur within 1 year in ≈20% of surviving patients, and major coronary events occur in ≈50% of patients with previous MI.^110,111 It is known that cardiac rehabilitation (CR) improves exercise capacity, coronary risk factors and quality of life (QOL); in addition, it reduces cardiovascular recurrence/mortality and total mortality.^6,112–114 It is important to continue CR seamlessly from the acute phase to the maintenance phase, but although outpatient CR reduces cardiovascular mortality, it does not improve total mortality.⁹⁶ CR is recommended as Class I in the “2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction”,¹¹⁵ the “2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes”,¹¹⁶ the “2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST elevation”,¹¹⁷ and the “JCS 2018 guideline on diagnosis and treatment of acute coronary syndrome”.¹⁰⁹

1.2.1 Acute Phase

In patients with severe circulatory failure, respiratory rehabilitation, prophylactic positional management, and prone therapy in addition to early CR should be performed within 3 days because physical function decline after ICU discharge (ICU-AW) affects QOL after discharge. Subsequently, the patient should be able to safely do basic self-care and education for secondary prevention should be started. Although bedrest does reduce the increase in heart rate and myocardial oxygen consumption, excessive bedrest is detrimental to the body’s condition.¹¹⁸ Rehabilitation is also useful in preventing orthostatic hypotension and thrombus formation associated with bedrest.¹⁰⁹

In patients with adequate reperfusion after percutaneous coronary intervention (PCI) and no need for life support, bedrest should be minimized and limited to 24 h without complications.¹¹⁹ CR should be started after confirming the highest creatine kinase or troponin level after PCI. If the patient is able to pass the walk test, he/she should be transferred from the CCU/ICU to the general ward. If there is a high risk of cardiac rupture during the acute phase, exercise training with increased blood pressure should not be performed.¹⁰⁹

1.2.2 Early Recovery Phase

The purpose of CR during this period is to return to work and society. It involves comprehensively and systematically performing (1) prognostic risk assessment by exercise stress test, (2) regular exercise training based on an exercise prescription, (3) secondary prevention education including lifestyle improvement, and (4) return to work and psychological counseling, etc. During hospitalization, patients are encouraged to get out of bed according to the program, and when they are able to walk 200 m without myocardial ischemia, they are transferred to endurance training. The exercise stress test is performed before or early after discharge to assess prognosis, prescribe physical activity, and determine the effects of medical therapy and PCI.¹⁰⁴ Because the length of hospital stay has been shortened, it is necessary to select a program that suits the patient and facilitates a smooth transition to secondary preventive education and rehabilitation in the late recovery phase.

1.2.3 Examples of Inpatient Programs for AMI

An example of an inpatient rehabilitation program (clinical path) is shown in Table 22.¹⁰⁹ Staged progression to the subsequent stage follows the criteria in Table 23. The time periods in the pathway are approximate and may be shortened or extended depending on the status of progression. The use of a clinical pathway can help standardize care and thereby improve the quality of care.¹⁰⁹ The ESC guidelines suggest that low-risk patients (age ≤70 years, LVEF >45%, 1- or 2-vessel disease, successful revascularization, no persistent arrhythmia) should be considered for discharge within 48–72 h.^120–122 Automatic referral is a program in which patients who require outpatient CR are automatically selected and the necessary procedures for participation in CR are performed before discharge; such an automatic referral may improve the participation rate¹²³ and offer a seamless shift to the outpatient CR program.

Table 22. A Clinical Pathway for CR for AMI (National Cerebral and Cardiovascular Center)

Day	10 day pathway	Day 1 after PCI	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8	Day 9	Day 10
	14 day pathway								Days 8–10	Days 11–13	Day 14
Goals		Prevent complications of AMI and catheter- related complications		Prevent complications of AMI	No myocardial ischemia	• No myocardial ischemia • Patient can take the prescribed drugs • Patient can access information about important points for daily living after discharge			• No myocardial ischemia • Patient can understand important points for daily living after discharge	• No ischemia at submaximal exercise • Patient can list important points for daily living after discharge	Discharge
Bed rest level		After tourniquet removal, allow the patient to move freely on the bed	Allow the patient to move freely in the room	Allow the patient to walk to the toilet, after passing a stress load test	Allow the patient to walk around the ward within a 200-m radius of the room (encourage walking 200 m × 3 times/day)		After passing a submaximal stress test, allow bathing and walking freely in the rehabilitation ward
Hygiene		• Face washing with assistance • Body cleaning	• Face washing: using the sink • Body cleaning, hair washing, foot bathing		• Face washing: using the sink • Cleansing: assistance with the back only and hair washing		Shower bathing
Patient education		• Explanation based on the AMI brochure and patient path 　- Rest degree, double stress avoidance 　- Nurse call when symptoms appear • Bowel control		• Explanation of rest degree, double stress avoidance, bowel control • Explanation of CR • Explanation of important points for daily living • Medication counseling, self-administration			• How to get emergency consultation • How to manage when having heart attack • Explanation of medication, diet, and smoking cessation		• Confirm instructional content
Patient care/stress test	10-day pathway	• Blood sampling (every 3 h until CK maximum value is reached) • ECG (every 6 h) • Echocardiography • Continuous heparin • Sheath removal • Tourniquet removal	• Blood sampling • ECG (every 6 h) • Echocardiography • Discontinue heparin • Remove the urinary catheter	• ECG (once daily) • 50-m walking stress testing	• ECG (once daily) • 200-m walking stress testing	Day 5	Day 6	Day 7	Day 8	Day 9
						• ECG (once daily) • Entry testing for CR	• ECG (once daily) up to day 7 • Conduct exercise sessions in the CR room (if the patient has not attended the program, conduct a Master’s single test or allow having a bath as a trial)
	14-day pathway					Day 5	Day 6	Day 7	Days 8–10	Days 11–13
						• ECG (once daily) • Entry testing for CR (if the patient has not attended the program, conduct a 500-m walking stress testing on day 6)		• ECG (once daily) up to day 7 • Conduct exercise sessions in the CR room (if the patient has not attended the program, conduct a Master’s single test or allow having a bath as a trial)

AMI, acute myocardial infarction; CK, creatine kinase; CR, cardiac rehabilitation; ECG, electrocardiogram; PCI, percutaneous coronary intervention. (Adapted from Japanese Circulation Society, 2019.¹⁰⁹)

Table 23. Criteria for Evaluating the Staging up of CR for Patients With AMI

1. No perceived symptoms such as chest pain, dyspnea or palpitation

2. No increase in HR to ≥120 beats/min or by an increase of ≥40 beats/min

3. No development of potentially dangerous cardiac arrhythmias

4. No ischemic ST depression ≥1 mm, or significant ST elevation

5. No change in systolic blood pressure ≥20 mmHg during the period before the patient was allowed to use a bedside commode

(the criteria for blood pressure are not used for patients 2 weeks after the onset of AMI)

Patients who fail the exercise stress test should receive appropriate drug treatment or other measures, and undergo the same test on the following day. AMI, acute myocardial infarction; HR, heart rate.

1.2.4 Late Recovery Phase

The purpose of CR during this period is to reissue the exercise prescription based on the exercise stress test after hospital discharge, to evaluate the effect of treatment, to predict prognosis, and to conduct nutritional and psychological evaluations as well. The final step is self-management, including exercise programs, and re-instruction of not only exercise habits but also lifestyle habits that have been corrected, to ensure a smooth transition to the maintenance phase (Figure 4). After discharge from hospital, the desirable frequency of outpatient clinic is about once every 2 weeks, and a comprehensive program including exercise, smoking cessation, diet, and lifestyle intervention is provided to attain the pre-disease ADL. For exercise training, the duration and frequency of exercise should start at 10 min twice daily, with a gradual increase to 20–30 min twice daily, and an aim of 30–60 min twice daily in the stable phase; finally, a goal of at least 3 times per week, and preferably daily is desirable. In older patients, sufficient time for preparatory exercise should be taken to prevent cardiac events, trauma, and falls during exercise.

Figure 4.

CR program used in the National Cerebral and Cardiovascular Center for patients with AMI in the recovery phase.

• On Day 4 of the clinical pathway, a 200-m walk test should be conducted, and patients who pass the test should attend a recovery-phase rehabilitation program in the CR room from Days 5–7 onwards.

• After discharge, patients should attend outpatient supervised exercise training programs while continuing home-based exercise training programs.

• CPX and a blood test should be performed at 1 week and at 3 months after the introduction of CR to assess exercise capacity and coronary risk factors and to prescribe an exercise training program.

AMI, acute myocardial infarction; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation.

1.2.5 Maintenance Phase

The purpose of CR during this period is to prevent recurrence, to maintain the adequate physical and mental function obtained in the recovery phase, and to continue lifelong rehabilitation. CR is incorporated into daily life, and exercise training is provided at home or at a local exercise facility; secondary prevention through diet and smoking cessation is continued. Because the Japanese insurance coverage period is 150 days, it is necessary to design a program that can provide CR in the maintenance phase.

1.3 Resistance Training

Early resistance training can be safely performed even after STEMI; it improves QOL, exercise capacity, and endothelial function.^124,125 The exercise prescription is 30–40% of 1 repetition maximum (RM) for upper extremity exercise, 50–60% for lower extremity exercise, with a load amount that can be repeated 10–15 times per set, with moderate fatigue, and a Borg scale of 11–13 “slightly strenuous” at the upper limit of 2–3 times per week. The resistance training uses rubber bands, ankle and wrist weights, dumbbells, free weights, pulleys, weight machines, and consists of 1–3 of 8–10 different exercises for the upper and lower extremities.

1.4 Current Status and Issues

The participation rate in outpatient CR after AMI is not high, even in Western countries, with 14–35% in the USA, 29% in the UK, and 23% in France, but it is remarkably low in Japan at only 4–8%.^126,127 Factors that contribute to participation in exercise training include external factors (safety, transportation, and social support), internal factors (physical function, cognitive function, and emotion), and cultural factors, with cognitive function and social factors being particularly important.¹²⁸ The percentage of ACS patients who are recommended to have CR by their physicians has been as low as 32%.¹²⁹ In the future, it is necessary to enhance outpatient CR facilities and to create a simple and easy introduction system for patients to participate.

The American Association of Cardiovascular and Pulmonary Rehabilitation (AACPR)/AHA/ACC has issued a statement on the introduction of Home-Based CR,¹³⁰ which should be considered for patients who have difficulty visiting a hospital for outpatient CR.

2. Stable Angina Pectoris With/Without PCI (Table 24)

Table 24. Recommendations and Levels of Evidence for CR in Patients With Stable Angina Pectoris

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform comprehensive CR for patients with SAP unless contraindicated	I	B	B	II
It is recommended to perform comprehensive CR for patients with CAD after elective PCI unless contraindicated	I	A	A	I
Exercise training alone or in combination with a disease management program should be considered to improve anginal symptoms	IIa	B	B	II
Performing the exercise stress test 1–3 days after PCI and initiating exercise training should be considered	IIa	B	C1	II

CAD, coronary artery disease; COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence; PCI, percutaneous coronary intervention; SAP, stable angina pectoris.

2.1 Pathology and Indications

CR is useful for any coronary artery disease (CAD), not only after AMI, but also after PCI such as after MI, stable/unstable angina, and after coronary artery bypass grafting (CABG).^131,132 For stable angina, increased daily activity is closely associated with lower all-cause/cardiovascular death.^131,132 The CR program includes comprehensive nutritional counseling, psychological counseling, management of coronary risk factors and exercise training, to reduce cardiovascular events while improving QOL by improving exercise capacity. In addition, CR has been reported to improve residual risk.^133,134 In low-risk patients (1- or 2-vessel disease excluding proximal left anterior descending branch disease), the J-SAP study in Japan showed no significant difference in cardiac death or ACS incidence between the PCI group and the medical treatment group during a 3-year follow-up.¹³⁵ In the COURAGE study in Europe and the USA, there was no significant difference in death or non-fatal MI in 3 years between patients with stable CAD who received optimal medical therapy alone, including lifestyle intervention such as exercise, diet, and smoking cessation, and those who received optimal medical therapy plus PCI.¹³⁶ The results suggest that PCI alone is insufficient to improve the prognosis of patients with stable angina, and that comprehensive management with exercise training is important.

2.2 Effect on Cardiovascular Events and Prognosis

The level of evidence for the efficacy of exercise training for stable angina is not as high as for AMI. Based on the evidence to date, the ACC/AHA^131,137 and ESC¹³² guidelines for angina pectoris recommend it as Class I, while the UK National Institute for Health and Care Excellence (NICE) guidelines for stable angina state that, although short-term effects of diet and exercise have been studied, there is little research on recurrence and prognosis, and there is no clinical or medical economic evidence for CR in angina.¹³⁸ A Cochrane review showed that CR improved the rate of revascularization, exercise capacity, and cardiovascular hospitalization in patients with stable angina, but did not reduce all-cause death or the incidence of MI.¹³⁹ Among patients with angina, those with low exercise capacity, residual symptoms on exertion, and low cardiac function in particular are good candidates for CR.

2.3 Effect on Angina Symptoms

Exercise training improves exercise capacity, raises the ischemic threshold, and improves QOL.^131,132 These mechanisms include direct improvement of coronary artery endothelial cell function and indirect improvement of dyslipidemia and antihypertensive effects, which may improve vasodilation, coronary flow reserve, and myocardial perfusion, which is reduced by ischemia. Interventional trials using exercise training and lifestyle modification have shown that exercise training improves angina symptoms and inhibits or improves the progression of coronary artery stenosis.^140,141 Interventional trials with exercise training and lifestyle modification have been shown to reduce or improve the progression of coronary artery stenosis as well as improve angina symptoms.¹⁴²

2.4 Indications After PCI

Although there is some evidence for CR in patients after PCI, there are no clear criteria regarding the timing of CR in the ACCF/AHA Guidelines “Core components of cardiac rehabilitation/secondary prevention programs: 2007 Update”¹⁴³ or in the European Association of Cardiovascular Prevention and Rehabilitation (EACPR) “Secondary prevention through cardiac rehabilitation: from knowledge to implementation”.¹⁴⁴ Balady et al reported that exercise testing to a mean of 71% of the predicted maximum HR within 3 days (mean 38 h) of uncomplicated PCI resulted in no cardiac events within 48 h and a faster return to work compared with the non-exercise group.¹⁴⁵ Soga et al reported on 800 patients who underwent submaximal-load (Borg scale 11–13) CPX on the day after stent implantation and early introduction of exercise training, and the acute event rate was similar to that of the control group, suggesting that it can be performed safely.¹⁴⁶ CR can be started the day after PCI, and exercise training can be started immediately if the intensity of exercise is less than 6–7 METs.

2.5 Exercise Training in Practice

Exercise training should be based on the results of CPX, and an individualized program should be implemented for each patient. The recommended exercise is moderate- to high-intensity aerobic exercise for 30–60 min/day, at least 5 days per week.^143,144 Exercise intensity should be limited to 70–85% of the HR at which ST depresses 1 mm or at 10 beats/min lower HR for asymptomatic myocardial ischemia. The intensity should be aimed at the anaerobic threshold (AT: 40–60% of peak V̇O₂), Karvonen’s formula [(maximum HR − resting HR) × (0.4 − 0.6) + resting HR], and a rating of perceived exertion (RPE) Borg scale of 11–13 (Table 25). A supervised exercise program is desirable in patients with low cardiac function, heart failure symptoms, low exercise threshold, and high residual ischemia.

Table 25. Setting of Exercise Intensity in CR for Patients With Angina Pectoris and After PCI

• If asymptomatic myocardial ischemia, 70–85% of the HR at which ST depresses 1 mm, or 10 beats/min lower HR

• AT level (≈40–60% of peak V̇O2)

• Karvonen’s formula [(maximum HR − resting HR) × (0.4 – 0.6) + resting HR]

• Target of the RPE: Borg scale 11–13

AT, anaerobic threshold; HR, heart rate; peak V̇O₂, peak oxygen uptake; RPE, rating of perceived exertion.

The main type of exercise should be endurance exercise; careful stretching and warm-up exercises are important to prevent angina attacks during exercise. Combination resistance training with dead weight and cool down is used. Other types of exercise and sports can be included if the intensity is below 60% of the AT level or maximal exercise capacity and does not cause ischemic signs. In a meta-analysis, resistance exercise performed 2–3 times per week in addition to aerobic exercise was shown to be more effective than aerobic exercise alone in reducing body fat and improving upper and lower limb muscle strength in CAD patients. In addition, cardiopulmonary function and QOL are known to improve.¹⁴⁷

Before the start of CR, it is important to evaluate the presence or absence of coronary artery stenosis (complete revascularization), which defines the oxygen supply, and the presence or absence of comorbidities or conditions, such as heart failure, that can cause hypoxia. It is also important to watch for excessive increases in blood pressure and HR during exercise. Whenever possible, CPX should be performed, and exercise training should be performed according to the exercise prescription.

3. Acute/Chronic Heart Failure

3.1 Acute Heart Failure (Acute Phase to Early Recovery Phase) (Table 26)

Table 26. Recommendations and Levels of Evidence for CR in Patients With Acute HF

	COR	LOE	GOR (MINDS)	LOE (MINDS)
An educational program on relapse prevention and self-management is recommended for all patients with acute heart failure	I	C	C1	VI
Early ambulation is recommended to shorten hospital stay and prevent ADL decline with attention to hemodynamic deterioration	I	C	B	IVa
For all patients with acute heart failure, CR programs should be considered after the patient’s condition has stabilized	IIa	C	C1	VI
After the stabilization of hemodynamic condition, exercise training should be considered	IIa	C	C1	IVb
Rehabilitation, such as low-intensity resistance training under close supervision, may be considered for hemodynamically stable patients with heart failure receiving intravenous inotropic drugs	IIb	C	C1	V

ADL, activities of daily living; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

3.1.1 Purpose and Effect

The purpose of CR for patients with acute heart failure (HF) is to (1) prevent the adverse effects of prolonged bed rest (e.g., decline in physical function, decline in cognitive function, delirium, pressure ulcers, pulmonary embolism) due to early ambulation, and (2) develop and implement a plan for early and safe discharge and for the prevention of rehospitalization. In particular, early initiation of CR for older HF patients is associated with a shorter hospital stay,¹⁴⁸ maintenance of ADL at discharge, and the prevention of rehospitalization after discharge.¹⁴⁹ Continuation of exercise training has been proven to improve the long-term prognosis,^150,151 so it is extremely important to motivate patients to participate in CR and to continue CR after discharge.

3.1.2 Ambulation Program

The ambulation program should proceed from the early stage of hospitalization, while confirming that hemodynamic values do not deteriorate, to prevent deterioration of physical function and deconditioning due to excessive rest. The specific ambulation program is shown in Table 27. For severe patients who cannot be weaned from catecholamines, the introduction of low-intensity resistance training on the bed to maintain muscle strength and combination of Waon therapy are considered. Patients with low ADL before admission, such as frail patients, are transferred to the rehabilitation room after intravenous infusion management is completed, and strength training and training for independence in ADL are performed. (For details, see Chapter V.1. Older Patients With Heart Disease.)

Table 27. Acute Phase Ambulation Program for Patients With Acute HF

Stage	Permissible degree of rest	Rehabilitation venue	Target sitting period* (total hours/day)	Stage up loading test
1	Bed rest	On bed	Reclined seating	Sitting upright
2	Sitting upright	Bedside	1 h	Walk test (free speed) 10 m
3	Free within room	Bedside	2 h	Walk test (free speed) 40 m
4	Walk to toilet	Ward	3 h	Walk test (free speed) 80 m
5	Walk freely within ward (up to 80 m)	Ward (rehabilitation room)	3 h	Walk test (free speed) 80 m × 2–3 times
6	Walk freely within ward	Ward (rehabilitation room)	3 h	6-minute walk test

*It is important not to place the patient in bed rest unnecessarily. HF, heart failure. (Adapted from Izawa H, et al, 2019¹⁰ with modification.)

3.1.3 Exercise Program

After the patient has progressed through the ambulation program and is able to perform the 6-minute walk test, exercise training should be initiated, making sure that there is no exacerbation of HF symptoms and no contraindication to exercise training (Table 28).¹⁰ As an exercise program, warm-up and cool-down are set before and after the exercise, which consists of low-intensity aerobic exercise and resistance training.¹⁰ The aerobic exercise should be started at a low intensity of 5–10 min of indoor walking or 0–20 W × 5–10 min of work rate on a bicycle ergometer, and the frequency and duration of exercise should be gradually increased according to the progress of perceived symptoms and physical findings. A Borg scale of 11–13 should be used as the initial exercise intensity. Resistance training is performed with rubber bands, ankle and wrist weights, dumbbells, and free weights, and is based on low intensity with a Borg scale of ≤13. The number of repetitions and sets are gradually increased, starting with 5–10 repetitions per set.

Table 28. Contraindications of Conditions and Symptoms for Exercise Training in Patients With HF

Absolute contraindications

1. Exacerbation of perceived symptoms within the previous 3 days

2. Unstable angina or low-threshold myocardial ischemia

3. Severe valvular heart disease indicated for surgery, especially symptomatic aortic stenosis

4. Severe left ventricular outflow tract obstruction

5. Poorly controlled arrhythmias causing hemodynamic abnormalities (ventricular fibrillation, sustained ventricular tachycardia)

6. Active myocarditis, pericarditis, endocarditis

7. Acute systemic disease or fever

8. Other diseases in which exercise is contraindicated (acute aortic dissection, moderate or severe aortic aneurysm, severe hypertension, thrombophlebitis, embolism that developed in the recent 2 weeks, and serious multiple organ damage

Relative contraindications

1. NYHA Class IV

2. Exacerbation of perceived symptoms or increase in body weight ≥2 kg in the previous week

3. Moderate left ventricular outflow tract obstruction

4. Tachyarrhythmia or bradyarrhythmia with poorly controlled HR with hemodynamic preservation (nonsustained ventricular tachycardia, tachycardiac AF, tachycardiac atrial flutter, etc.)

5. Advanced atrioventricular block

6. Exacerbation of exercise-induced perceived symptoms (fatigue, dizziness, excessive sweating, dyspnea, etc.)

Note: “Exercise training” refers to aerobic exercise and resistance training with sufficient exercise intensity for the purpose of improving exercise capacity and muscle strength. AF, atrial fibrillation; HF, heart failure; HR, heart rate. (Source: based on Izawa H, et al, 2019.¹⁰)

3.2 Chronic Heart Failure (Late Recovery Phase to Maintenance Phase)

Comprehensive CR, including exercise training, is one of the most important treatments for HF because it not only improves exercise capacity and QOL in patients with chronic HF,¹⁵⁰ but also leads to left ventricular reverse remodeling,¹⁵² improved autonomic function,¹⁵³ improved vascular endothelial function,¹⁵⁴ and reduced rates of HF and rehospitalization for all causes.^150,151 It is considered one of the most important treatments for HF.

3.2.1 Assessment of Exercise Capacity (Table 29)

Table 29. Recommendations and Levels of Evidence for the Methods of Exercise Capacity Assessment in HF Patients Undergoing CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to assess NYHA classification, exercise capacity, psychological status, comorbidities, cognitive ability, and social environment, by interview	I	B	B	IVa
It is recommended to use CPX to assess the severity and prognosis of HF, to determine the effectiveness of treatment and to determine the indications for heart transplantation and other therapies	I	B	B	II
It is recommended to use CPX to differentiate between causes of dyspnea and easy fatigability during exertion	I	B	B	IVb
Assessment of sarcopenia and frailty should be considered in patients suspected of having either	IIa	B	B	IVa
If CPX cannot be performed, 6MWD should be considered to evaluate prognosis and determine the effect of treatment	IIa	B	B	II
It should be considered to use CPX to develop the exercise prescription	IIa	B	B	II

COR, class of recommendation; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

Methods of evaluating exercise capacity in HF patients include the NYHA classification, questionnaires such as the Specific Activity Scale (SAS), the 6-minute walk distance (6MWD), and cardiopulmonary exercise testing (CPX). Evaluation of exercise capacity is used to predict the prognosis, stratify risks associated with exercise training, determine exercise prescription and its effects, and determine indications for and effects of heart transplantation and other advanced therapies. The 6MWD is also a popular method for assessing exercise capacity in HF patients because it does not require special equipment. The 6MWD correlates with peak V̇O₂ and it is as prognostic as peak V̇O₂ and the V̇E vs. V̇CO₂ slope,¹⁵⁵ and thus it is used to determine the efficacy of various therapies.¹⁵⁶ In older patients, the 6MWD is related to respiratory, circulatory, and metabolic functions, as well as to limiting factors specific to older patients, such as lower limb muscle strength and balance.^156–158 In addition, in older patients with heart disease, usual gait speed and 6MWD show a strong positive correlation,^159,160 and the prognostic value is also reported to be similar.¹⁵⁹

3.2.2 Significance and Effectiveness (Table 30)

Table 30. Recommendations and Levels of Evidence for CR in Patients With Chronic HF

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In patients with HFrEF, it is recommended to use exercise training to improve subjective symptoms and exercise capacity, improve QOL, and reduce rehospitalizations	I	A	A	I
A comprehensive CR program with a multidisciplinary team should be considered for all patients without contraindications	I	A	A	I
Exercise training should be considered to improve the life expectancy of patients with HFrEF	IIa	B	B	II
In patients with HFpEF, exercise training should be considered to improve subjective symptoms and exercise capacity	IIa	B	A	I
In patients with advanced deconditioning or reduced physical function, resistance training should be considered to improve ADL and QOL	IIa	C	B	IVb

Note: For patients receiving intravenous inotropic drugs, see Tables 26 and 51. ADL, activities of daily living; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LOE, level of evidence; QOL, quality of life.

The major mechanisms of reduced exercise capacity in HF with reduced ejection fraction (HFrEF) are mainly peripheral factors such as skeletal muscle mass loss, metabolic abnormalities, decreased vasodilatation, and increased ergoreceptor reflex¹⁶¹ It has been suggested that skeletal muscle damage is one of the limiting factors for exercise capacity in HF with preserved ejection fraction (HFpEF).¹⁶² Improvement in exercise capacity in HF patients is mainly due to improvement in peripheral function.¹⁶³

CR based on exercise training for HFrEF is effective in improving prognosis,^106,151 exercise capacity, and QOL,¹⁶⁴ and reducing the risk of all-cause rehospitalization,¹⁵⁰ and the risk of rehospitalization for HF.^150,151 In HFpEF, exercise training has been shown to improve peak V̇O₂ and QOL, and to be associated with better prognosis^151,165 A multicenter, retrospective observational study in Japan¹⁵¹ found that CR participation was associated with a higher risk of events in patients with HFpEF and mild to moderate frailty, regardless of age, sex or comorbidities.¹⁶⁶ Because the rate of uptake of outpatient CR in patients with HF is extremely low in Japan, widespread use of CR is a major challenge.

3.2.3 Indications, Contraindications, and Safety

Exercise training is indicated for patients with stable, controlled HF without worsening of perceived symptoms or physical findings of HF in at least the recent 3 days, without excessive fluid retention or dehydration, and with NYHA class II–III.

The absolute and relative contraindications to exercise training in HF are listed in Table 28. In some patients with NYHA class IV, low-intensity resistance training, ADL exercises, and local skeletal muscle training such as neuromuscular electrical stimulation are applicable.^78,167 Older age, reduced LVEF, using a supplemental cardiac assist device, and after implantation of an implantable cardioverter defibrillator (ICD) are not contraindications for exercise training.

Fatal events directly related to exercise training for HF have not been reported in exercise training for HF in more than 60,000 person-hours.⁹⁸ The incidence of major cardiac events does not differ between the exercise training group and non-exercise training group.^102,106 According to a report from Japan,¹⁶⁸ the incidence of cardiac events (worsening HF, hypotension, arrhythmia) that caused patients to drop out of the program was 5% in exercise training for patients with moderate to advanced HF with an average LVEF of 25%, and the incidence of cardiac events that required temporary suspension of exercise training was 8%. Predictors of cardiac events are listed as left ventricular enlargement (end-diastolic diameter ≥65 mm), high BNP, poor exercise capacity, increased ventilation during exercise, and after implantation of a pacemaker or ICD.

3.2.4 Exercise Program (Table 31)

Table 31. Recommendations and Levels of Evidence for Individualized CR Programs for Patients With Chronic HF

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to provide individualized exercise and physical therapy to patients with reduced physical function	I	B	A	II
Comprehensive CR program from a multidisciplinary team is recommended for all patients without contraindications	I	A	A	I
In patients who are deconditioned and have difficulty with exercise training, neuromuscular electrical stimulation of lower extremity skeletal muscles should be considered	IIa	B	B	I
Inspiratory muscle training should be considered for patients with decreased inspiratory muscle strength	IIa	B	B	I
High-intensity interval training may be considered to improve exercise capacity in patients with low-risk, stable HFrEF	IIb	B	C1	II

Note: There are few reports on high-intensity interval training, neuromuscular electrical stimulation, and respiratory muscle training in Japan. COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HFrEF, heart failure with reduced ejection fraction; LOE, level of evidence.

Exercise training for chronic HF is basically performed according to the exercise prescription (Table 32).¹⁰ It should be performed under supervision, especially in older patients, those with markedly reduced left ventricular function, and those with potentially dangerous arrhythmias or ischemia. In low-risk stable patients who have not had an exacerbation of HF for more than 2–3 months and who can safely perform the above-listed intensity exercise, prescriptions for higher intensities, such as 60–80% of peak V̇O₂,^102,168 or high-intensity interval training (HIIT),^82,169,170 it should be considered under supervision. (For more information on HIIT, see Chapter III.2.3 High-Intensity Interval Training.)

Table 32. Exercise Program for Patients With Chronic HF

Composition

An exercise program consisting of aerobic and resistance exercise, including warm-up before exercise and cool-down after exercise

Aerobic exercise

The frequency, intensity, duration, and modality of aerobic exercise will be prescribed based on the results of CPX

• Modality: walking, bicycle ergometer, treadmill, etc.

• Frequency: 3–5 times per week (≈3 times per week in severely affected patients)

• Intensity: 40–60% of peak V̇O2, 30–50% of HRR, 50–70% of maximal HR, or HR at the AT

→ In low-risk patients stable for at least 2–3 months without worsening HF and can safely perform the above-intensity exercise program, consider prescribing higher intensity under supervision (e.g., equivalent to 60–80% of peak V̇O2, or HIIT)

• Duration: Start with 5–10 min twice daily and gradually increase to 20–30 min/day. Be careful not to exacerbate HF

If CPX cannot be performed

• Intensity: Borg scale 11–13, HR at rest +20–30 beats, and HR during exercise is less than 120 beats/min

• Modality, frequency, and duration are the same as for exercise prescription based on the results of CPX

Resistance training

• Modality: rubber bands, ankle and wrist weights, dumbbells, free weights, weight machines, etc.

• Frequency: 2–3 times per week

• Intensity: Low to moderate intensity

30–40% of 1RM for upper extremity exercises, 50–60% of 1RM for lower extremity exercises, with a load capacity of 10–15 repetitions per set, Borg scale ≤13

• Duration: 1–3 sets of 10–15 repetitions

Indicators suggesting an excessive exercise load

• Suspected fluid retention for weight gain ≥2 kg in 3 days (immediate response) and 7 days (increased surveillance)

• Decrease in systolic blood pressure ≥20 mmHg despite gradual increase in exercise intensity, with symptoms/signs of poor peripheral circulation, such as peripheral coldness

• Exacerbation of perceived chest symptoms at the same exercise intensity

• Increase in HR by ≥10 beats/min, or increase in Borg scale by ≥2 levels at the same exercise intensity

• Decreased transcutaneous arterial oxygen saturation to <90% or decreased by ≥5% from rest

• Appearance of new arrhythmia or ST depression ≥1 mm on ECG

Precautions

• As a general rule, exercise should be performed under supervision at the beginning, and should be performed with a combination of supervised and non-supervised (home exercise training) in the stable period

• During the course, always pay attention to perceived symptoms, and changes in body weight and blood BNP or NT-proBNP levels

• Exercise capacity should be assessed periodically by symptom-limited exercise test, and exercise prescription should be reviewed

• Check for the presence of new comorbidities (orthopedic disease, PAD, cerebrovascular/neurological disease, pulmonary disease, renal disease, psychiatric disease, etc.) and changes in treatment that may affect exercise

AT, anaerobic threshold; CPX, cardiopulmonary exercise testing; HR, heart rate; HRR, heart rate reserve; PAD, peripheral arterial disease; peak V̇O₂, peak oxygen uptake; RM, repetition maximum. (Source: based on Izawa H, et al, 2019.¹⁰)

For patients with reduced physical activity capacity due to sarcopenia or frailty, individualized exercise and physical therapy based on the results of individual patient assessment may possibly improve exercise capacity and reduce the risk of rehospitalization for HF.^151,171 Various types of training are effective for patients who are unable to undertake adequate exercise training.^78,167,172 (For information on CR for older people, see Chapter V.)

3.2.5 Periodic Observation and Evaluation

The appropriateness of exercise training for chronic HF is assessed from the perspective of both efficacy and safety (Figure 5).¹⁷³ Exercise capacity assessments, such as peak V̇O₂ and 6MWD, motor function indices such as the Short Physical Performance Battery, gait speed, and overall muscle strength, ADL and instrumental ADL (IADL) indices, and health-related QOL (HRQOL) indices (Kansas Cardiomyopathy Questionnaire, SF-36, etc.), are used depending on the patient’s goals.^174,175 It can be said that the effect of exercise training is evident if exercise capacity is maintained.

Figure 5.

Exercise training and disease management for heart failure patients in ambulatory CR programs. 6MWD, 6-minute walk distance; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; HR, heart rate. (Adapted from Goto Y, 2014¹⁷³ with modifications.)

From a safety standpoint, hemodynamic indices and symptoms during and before/after exercise, daily monitoring of HF signs, and periodic BNP (NT-proBNP) measurement should be used to guide the outpatient CR with reference to indicators of overloading (Table 32). In addition, the CR team plays a central role, because it is multidisciplinary and can examine the factors that exacerbate HF and provide patient education on these critical factors from different perspectives.^176,177 For details of patient education and management, see Chapters VII and VIII.

4. After Cardiac Surgery (Table 33)

Table 33. Recommendations and Levels of Evidence for CR After Cardiac Surgery

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Exercise training is recommended to improve perceived symptoms and exercise capacity and to correct coronary risk factors after CABG	I	A	A	I
Exercise training is recommended to improve perceived symptoms and exercise capacity in postoperative valvular heart disease	I	A	B	II
Exercise training should be considered to improve long-term prognosis after CABG	IIa	B	B	I
Early ambulation should be considered after cardiac surgery	IIa	B	B	I
A chest belt should not be worn routinely after cardiac surgery	III (Harm)	C	C1	IVb

CABG, coronary artery bypass grafting; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

4.1 Effectiveness

Exercise training after cardiac surgery has been proven as effective in various aspects, such as exercise capacity, coronary risk factors, autonomic activity, cardiac and peripheral function, QOL, mental health, rehospitalization rates, and healthcare costs, and thus is strongly recommended in the guidelines of Europe and the USA.^178,179 As a prognostic study, a meta-analysis of 18 randomized controlled trials (RCTs) of adults after cardiac surgery showed no mortality benefit from rehabilitation vs. usual care. However, a systematic review of 15 prospective observational studies showed that total mortality was significantly lower in the rehabilitation group.¹⁸⁰ Results of a Japanese multicenter study on the effectiveness of outpatient CR after CABG showed that major cardiovascular events, total rehospitalizations, rehospitalization for cardiac diseases, and coronary events were significantly lower in the active participation group than in the nonparticipation group.¹⁸¹ To date, there is no evidence of improved long-term outcomes after cardiac surgery other than CABG.

4.2 Rehabilitation in Practice

4.2.1 Acute Phase

Early postoperative rehabilitation is effective in improving physical function, HRQOL, peripheral skeletal muscle, respiratory muscle strength, duration of ventilator use, ICU stay, and hospital stay.¹⁸²

a. Criteria for Early Mobilization

When starting ambulation, refer to Table 34 and the criteria in the guideline of the Japanese Society of Intensive Care Medicine.¹⁸³ If the benefits of ambulation are judged to be significant, the patient should be able to get out of bed under close monitoring, even if all criteria are not met.

Table 34. Criteria for Early Mobilization

The patient can start to get out of bed if the following conditions are ruled out:

1. Condition of low output syndrome (LOS),

(1) the patient is wearing a life-support system such as a ventilator, intra-aortic balloon pumping device or percutaneous cardiopulmonary support device

(2) the patient is receiving a large amount of catecholamine such as noradrenaline

(3) systolic blood pressure is < 80–90 mmHg under catecholamine administration

(4) cold extremities and cyanosis

(5) metabolic acidosis

(6) urine output <0.5–1.0 mL/kg/h for >2 h

2. Swan-Ganz catheter insertion

3. Resting HR ≥120 beats/min

4. Unstable blood pressure (blood pressure decreases only by changing position)

5. Hemodynamically unstable arrhythmia (newly developed AF, ventricular arrhythmia with Lown IVb or greater)

6. Dyspnea or tachypnea at rest (respiratory rate >30/min)

7. Postoperative bleeding tendency continues

AF, atrial fibrillation; HR, heart rate.

b. Step-up Criteria

After the start of the ambulation process, the patient’s exercise protocol has proceeded step by step while checking the step-up criteria as follows: (1) no chest pain, severe shortness of breath, strong fatigue (Borg scale >13), dizziness, lightheadedness, or leg pain, (2) no cyanosis, pallor or cold sweat, (3) no tachypnea (≥30 breaths/min), (4) no increase in arrhythmia or rhythm change to AF with exercise, (5) no ischemic ECG change with exercise, (6) no excessive blood pressure changes with exercise, (7) no increase in HR by more than 30 beats/min with exercise, and (8) no decrease in arterial oxygen saturation to <90% with exercise.

c. Program Progression

A multicenter survey in Japan reported that the average number of days before independent walking after successful elective cardiac surgery was 3.8.¹⁸⁴ Currently, the standard program is to start standing and walking on the day after surgery and to achieve independence on the 4th day after surgery. Excessive progress of the program is prohibited; the program is modified according to the patient’s condition.

d. Causes of Rehabilitation Delay

Rehabilitation steps were delayed in 8.7–25.4% of patients after cardiac surgery,¹⁸⁵ because of prolonged HF, the appearance of new arrhythmias, preoperative loss of motor function, acute renal injury, and the development of cerebral complications. Among these, postoperative AF occurred at a high rate of 25–40% and it was associated with postoperative lower limb dysfunction.¹⁸⁶

4.2.2 Early Recovery Phase

In the recovery phase of rehabilitation, the goal is independence in walking, expansion of ADL, and social return. Therefore, in addition to improving exercise capacity, support is provided for the acquisition of self-management skills in post-discharge life.

a. When to Start Exercise Training

In general, aerobic exercise training using exercise equipment will be started when the patient is able to walk 200 m. Aerobic exercise can be safely performed from the 7th day after surgery in patients who are progressing well, leading to improvement in graft patency¹⁸⁷ and early recovery of exercise capacity.¹⁸⁸

b. Points to Consider When Starting

Exercise training should be started when the following conditions are met: (1) no fever, and inflammatory response is steadily improving, (2) no significant pericardial or pleural effusion, (3) no new AF, (4) anemia, but hemoglobin is ≥8 g/dL and has an improving tendency.

c. Aerobic Exercise

Exercise intensity is recommended to be at the aerobic exercise level, and if possible is set based on the AT calculated by CPX. Even at the AT level, if there is excessive blood pressure elevation or signs of myocardial ischemia, the intensity of exercise should be reduced. When CPX cannot be performed, symptom-limited exercise ECG should be performed, and the exercise prescription should be based on the target HR calculated by the Karvonen method. In the acute postoperative period, the patient often presents with chronotropic incompetence, which is defined as the inability to increase the HR adequately during exercise to match cardiac output to metabolic demands,¹⁸⁹ and the maximal HR should be measured by an exercise stress test. If none of the above can be performed, exercise training should be performed under close supervision with a Borg scale of 11–13 as a guide.

d. Resistance Training

For postoperative resistance training, it is recommended to combine multiple isotonic exercises rather than isometric training.¹⁹⁰ Training of the upper extremities should be avoided, due to possible overload during the first 3 months after surgery until bony fusion of the sternal incision is completed. As excessive rest can lead to soft tissue adhesions around the sternal incision, it is advisable to start some movement exercises to increase the range of motion within 24 h after surgery.¹⁹⁰ Resistance training for the lower extremities should be performed 2–3 times/week, with 10–15 repetitions at 30–50% of the maximum load.¹⁹¹

e. Protection After Median Sternotomy

Patients who have had a median sternotomy should be instructed to restrict upper extremity elevation load to no more than 5–8 pounds (2.27–3.63 kg) for 5–8 weeks after surgery.¹⁹² As a chest belt may adversely affect respiratory function by restricting thoracic motion, and contribute to pulmonary complications, it should not be worn routinely.¹⁹³ As an alternative to a chest belt, a sternal support band has been reported to be effective in protecting the sternum during body movements or coughing.¹⁹⁴

f. Patient Education

The patient education program at discharge should be given together with the patient’s family, including appropriate exercise training based on the exercise prescription, lifestyle modification, medication, diet, smoking cessation, self-monitoring, wound management, and emergency procedures.

4.2.3 Late Recovery Phase

Outpatient CR should be continued with the goal of social return and acquiring new lifestyle habits after discharge. A Japanese multicenter study reported that active participation in outpatient CR improves exercise capacity and long-term prognosis after CABG.¹⁸¹

4.2.4 Maintenance Phase

To maintain the physical function improvement during the acute and recovery phases of CR, it is essential to continue lifelong exercise training. Home programs conducted under medical control are as effective as those conducted in hospitals and other facilities.¹⁹⁵

4.3 Features and Cautions Following Each Surgical Technique

4.3.1 After CABG

It is essential to confirm the success or failure of complete revascularization before starting rehabilitation During rehabilitation, it is important to pay attention to chest symptoms and ECG changes in anticipation of early postoperative graft occlusion. Although off-pump coronary artery bypass (OPCAB) is less invasive and allows for faster postoperative exercise training than CABG with extracorporeal circulation, OPCAB is at times chosen for patients with a high preoperative risk, so a case-specific program should be developed.¹⁹⁶

4.3.2 After Surgery for Valvular Disease

As a caution after valve replacement, patients must understand the need for postoperative anticoagulation and the characteristics of the prosthetic valve selected. In recent years, valvuloplasty has been increasingly chosen, and there are a wide variety of methods available. Strict blood pressure control may be necessary to avoid pressure overload at the site of the valve, and information should be shared with the cardiac surgeon before rehabilitation.

4.3.3 After Minimally Invasive Cardiac Surgery

With the advances of devices, minimally invasive cardiac surgery (MICS) with small incisions has become popular. It has been reported that MICS patients gain the ability to stand and walk earlier postoperatively than those who underwent conventional median sternotomy.¹⁹⁷

5. After TAVI (Table 35)

Table 35. Recommendations and Levels of Evidence for CR Before and After TAVI

	COR	LOE	GOR (MINDS)	LOE (MINDS)
CR is recommended in the perioperative period	I	C	B	I
In patients who are suspected to be frail, assessment of frailty should be considered	IIa	C	C1	V

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; TAVI, transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI), a new treatment for aortic stenosis, became covered by insurance in Japan in 2018.¹⁹⁸ Many patients who are indicated for TAVI are contraindicated for conventional surgical aortic valve replacement (SAVR), such as in the very old and frail patients. Therefore, the role of CR in the perioperative period of TAVI is important to achieve better postoperative outcomes (Table 36).¹⁹⁹

Table 36. Role of CR for TAVI Patients

	Before TAVI	Postoperative acute phase	Recovery phase	Maintenance phase
Problem	• High risk older people • Majority are frail • Limited activity	• Perioperative management (anesthesia, analgesia) • Post-intensive care syndrome (delirium, cognitive impairment, etc.)	• Discharged while still recovering (postoperative complications, physical function)	• Continuation of preoperative lifestyle • Decline in physical function
Goal	• Maintenance of ADL • Improvement of nutritional status	• Early ambulation • Reestablishment of preoperative ADL • Reestablishment of daily functions	No frailty 　→ Improvement of exercise capacity With frailty 　→ improvement of muscle strength and balance ability • Establishment of daily life functions • Avoidance of secondary complications (falls, etc.)	• Maintenance and improvement of QOL • Cooperation with local medical care and welfare • Cooperation with multiple professions
Approach	• Frailty assessment • Nutrition intervention • Life function assessment • Build trusting relationships • Discharge and post- discharge social services 　Service review	• Smooth and early release from hospital • ADL expansion • Improvement of exercise capacity	No frailty • Extend walking distance • Aerobic exercise • Strength training With frailty • Strength training • Balance training • Walking training	• Home exercise training • Expansion of activity range • Enhancement of leisure time activities • Periodic assessment of frailty to deal with deteriorating patients • Recovery phase rehabilitation hospitals or home medical care, nursing care insurance, cooperation among private exercise facilities and local governments, etc.

CR, cardiac rehabilitation; QOL, quality of life; TAVI, transcatheter aortic valve implantation. (Adapted from Higuchi T, et al, 2019¹⁹⁹ with modifications.)

In addition to being frail in general, older patients who undergo TAVI have diverse backgrounds, such as low nutrition, dementia, and depression, and it is recommended that each case be evaluated by a heart team.^200,201 The characteristics of CR in post-TAVI patients include the absence of a mid-sternum incision, relative freedom to perform upper extremity and trunk exercises, and compared to SAVR, early walking training is possible. However, post-TAVI patients are often discharged from hospital earlier than those undergoing SAVR, so they do not spend enough time in early recovery phase CR. According to the report from Zanettini et al,²⁰² the average hospital stay for patients after TAVI is 11 days, and the average length of subsequent rehabilitation is 18 days. During a mean follow-up of 540 days after discharge, 20% were rehospitalized, 25% of which were due to CVD.²⁰² The need for comprehensive CR after discharge may also apply to patients after TAVI.

There are reports that CR after TAVI is as effective as CR after SAVR in improving exercise capacity and QOL,²⁰³ and that both the 6MWD and Functional Independence Measure (FIM) scores are significantly better than before TAVI at the time of hospital discharge (≈19 days after surgery).²⁰⁴ Although there are few reports of continued CR after TAVI, there is a report of significant improvement in exercise capacity, muscle strength, and QOL in an intervention group that continued exercise training combining aerobic exercise and resistance training 2–3 times/week for 8 weeks after TAVI.²⁰⁵ In the PARTNER study, the mortality rate at 2 years was 42.5%, 31.2%, and 28.8%, respectively, in three groups of “inability to walk,” “slow walk,” and “fast walk,” suggesting that CR intervention may improve prognosis.²⁰⁶

For CR after TAVI, serious complications specific to TAVI have already been resolved at the time of postoperative CR, but there are other complications, such as perivalvular regurgitation, and arrhythmias, such as atrioventricular block, and also injuries to the catheter access route. In the case of the transapical approach, pain at the anterior thoracic incision or drain site, and respiratory failure due to pleural effusion may occur, sometimes making it difficult to proceed with postoperative CR. Perivalvular regurgitation can cause HF if the regurgitant flow is high; even if there is no atrioventricular block immediately after surgery, atrioventricular block may occur several days later, so ECG monitoring during CR is important.

CR after TAVI can be performed with the same program as for post-open heart surgery;²⁰⁷ it generally proceeds sequentially with sitting at a bed side, standing, stepping stairs, and walking exercises. Although there are individual differences, patients start to stand up on the day after surgery (ICU), start walking on the second day (high care unit (HCU) or general ward), and start aerobic exercise using a bicycle ergometer or treadmill in the CR room from 3 to 5 days after surgery. In the older patients, postoperative delirium often interferes with CR. TAVI patients have many preoperative comorbidities, often including frailty, so it is advisable to implement an individualized program depending on physical function and ADL.^208,209 With the advancement in devices, the less invasive transfemoral approach is becoming more common, and as a result, earlier CR progression and hospital discharge have become possible. However, TAVI patients are often older and present with decreased physical function and ADL, requiring prolonged CR.²¹⁰ Therefore, it is important to collaborate with multiple professionals, including the recovery phase rehabilitation hospital staff and community services using care insurance; it is necessary to establish a medical care system in cooperation with home medical care, geriatric healthcare facilities, private exercise facilities, and local government.²¹¹

In the USA and Europe, TAVI has been reported to be effective in low-risk patients,²¹² so the number of TAVI patients is expected to increase in the future, and it will be necessary to establish appropriate CR programs based on individual case risk.

6. Arrhythmia, After Device Implantation

*The device in this section refers to a cardiac implantable electronic device (CIED).

6.1 Arrhythmia (Table 37)

Table 37. Recommendations and Levels of Evidence for CR in Patients With Arrhythmias

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In patients with AF who have poor exercise capacity or complicated HF, exercise training should be considered to improve exercise capacity and QOL	IIa	B	B	II
For AF patients complicated with obesity, body weight control and the management of other risk factors should be considered to reduce the burden and symptoms of AF213	IIa	B	A	II
Exercise training may be considered to improve exercise capacity after AF catheter ablation	IIb	B	B	II
Exercise training should not be performed for patients with ventricular arrhythmias contraindicated to exercise training	III (Harm)	C	B	IVa

AF, atrial fibrillation; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; QOL, quality of life.

When considering exercise training for arrhythmia, the presence or absence of underlying cardiac disease must first be considered. If there is underlying cardiac disease, CR including exercise training improves myocardial ischemia and suppresses the sympathetic nervous system, and thereby can be expected to prevent worsening and progression of the arrhythmia substrate.

6.1.1 Premature Ventricular Contractions (PVCs)

Regarding PVCs, the following factors should be evaluated for risk stratification: organic heart disease, cardiac function, mode of occurrence of arrhythmia (frequency, timing of occurrence, presence or absence of a series), and family history of hereditary arrhythmia. High risk is indicated by the following: frequency of PVCs >30/h, polymorphism, sustained extrasystoles more than triplet, R-on-T pattern, and a short coupling interval.²¹³ Increased PVCs during the exercise stress test is also a risk factor.²¹⁴ According to the AHA guidelines, when ≥3 consecutive PVCs or polymorphic ventricular tachycardia occur, discontinuation of exercise should be considered.

6.1.2 Atrial Fibrillation (AF)

The frequency of AF is increasing in Japan year by year, although it depends on age and underlying disease status. AF not only causes cerebral embolization, but also increases the risk of dementia, impaired mobility, HF, MI, and sudden cardiac death.²¹³ Compared with the forward progress in the treatment of AF, the prevention of AF onset has not made much progress. Attention is focused on the importance of managing lifestyle-related factors as modifiable clinical risk factors.^215–217 In addition to the evaluation of cardiac diseases, such as HF, CAD, and valvular heart disease, the Japanese Circulation Society guidelines (Class IIa, Evidence level B)²¹³ recommend assessing age, sex, hypertension, diabetes mellitus, obesity, sleep-disordered breathing, uric acid level, smoking, alcohol consumption, and genetic predisposition. It is thought that sustained stress on the atria changes the electrical and structural properties of cells and tissues, and causes the formation of substrates that promote the development and maintenance of AF (i.e., atrial remodeling).²¹³

The relationship between exercise and the risk of developing AF is complex and differs between the general population and athletes. The risk of developing AF is higher in athletes who have frequent endurance exercise events, such as endurance exercise three times a week for >10 years.²¹⁸ In contrast, in the general population, the level of activity in daily life is related to the onset of AF. A meta-analysis of 205,094 patients from 6 studies found that improved exercise capacity was associated with a 9% reduction in the risk of developing AF, with the lowest exercise capacity group having a higher risk of developing AF.²¹⁷ This suggests that exercise may reduce the risk of developing AF in the general population.

6.1.3 Efficacy of Exercise Training for AF Patients

a. Paroxysmal and Persistent AF

Malmo et al reported that in patients with paroxysmal or persistent AF, exercise training (including HIIT) contributed to a reduction in AF duration.²¹⁹ Though there is a report that no difference was found,²²⁰ there is also a report in patients with AF after catheter ablation showing that exercise capacity improved in the exercise group compared with the control group.²²¹ Kato et al conducted a RCT in 61 patients who returned to sinus rhythm after ablation of persistent AF, and reported that the exercise group showed significant improvement in 6MWD, grip strength, leg muscle strength, and high-sensitivity C-reactive protein compared with the control group, without an increase in the recurrence of AF.²²² Exercise training in patients with paroxysmal AF is safe and can improve exercise capacity, but further study is necessary to determine the evidence for its efficacy in reducing AF occurrence.

b. Chronic AF

In patients with chronic AF, exercise capacity can be significantly improved by exercise performed with an intensity of 60–90% of reserve capacity (Karvonen method k=0.6–0.9),²²³ or with an intensity of 70–90% of maximal HR three times/week.²²⁴ Regarding patients with concomitant HF, in the HF-ACTION study of patients with LVEF ≤35%, of the 382 AF patients, 193 had supervised exercise training 3 times/week for 3 months and then performed home exercise training for 2 years. As a result, the AF group showed similar improvements in exercise capacity and QOL as in the sinus rhythm group, although there was a problem with compliance.²²⁵

c. After Cardiac Surgery

AF after cardiac surgery occurs most frequently within 5 days of surgery, and particularly within the first 24–72 h after surgery.²²⁶ Postoperative AF is said to occur in 16–40% of patients after CABG, in 33–49% of patients after valvular surgery, and in 36–63.6% of patients after CABG plus valvular surgery.^226–228 Risk factors include advanced age, hypertension, history of AF, left atrial enlargement, HF, and chronic obstructive pulmonary disease (COPD), with advanced age being the most significant risk factor.²²⁶ Herdy et al randomized patients scheduled for CABG who were able to exercise for at least 5 days prior to surgery to an exercise group or a control group, and prospectively evaluated postoperative complications and hospital stay. Postoperative AF was significantly reduced in the exercise group (10% in the exercise group vs. 37% in the control group, P=0.03).²²⁹ Pulmonary complications and hospital stay were also significantly reduced in the exercise group. It is recommended to start CR before surgery and to resume it early after surgery to reduce postoperative AF.

6.1.4 Actual Exercise Training for Patients With AF

A flowchart of exercise training for patients with AF is shown in Figure 6. Because many patients with AF also have HF, it is important to evaluate the HF before considering whether exercise training is appropriate. In addition, because anticoagulation is often administered to prevent cerebral infarction, it is necessary to pay attention to hemorrhagic complications due to trauma, such as falls, adherence to medication, and anticoagulation control.

Figure 6.

Flowchart for exercise training in patients with AF.

*¹Perceived symptoms of heart failure (e.g., dyspnea, edema and anorexia), objective symptoms of heart failure (an increase in body weight of ≥2 kg within 1 week, decreases in SpO₂ at rest and immediately after exercise as compared with baseline, and pulmonary congestion and worsening of pleural effusion on X-ray), etc.

*²The feasibility of exercise training should be determined on the basis of the change in pulse rate, perceived symptoms, duration of exercise, and peak METs during exercise stress test. Physicians may define adequate rate control as a HR variability of ≤10 beats/min. Peak HR ≤150 beats/min.

*³In CPX, gait speed is calculated from the loading intensity at the AT and the METs during exercise. In a treadmill test, walking speed is calculated from 40–60% of the METs at the maximum exercise load.

*⁴Because the exercise intensity calculated from the maximum exercise load may not reach the AT level, if the load is judged to be insufficient after exercise training based on blood pressure, pulse rate, and subjective symptoms, the load intensity should be reexamined.

AF, atrial fibrillation; AT, anaerobic threshold; CPX, cardiopulmonary exercise testing; HR, heart rate; METs, metabolic equivalents.

a. Exercise Stress Test

When an exercise stress test is performed in patients with AF, ST depression occurs at a high rate together with an increase in HR. As for the cause of such ST depression, the effects of digitalis medication, left ventricular hypertrophy, and the possibility of myocardial ischemia should be considered. If the HR is poorly controlled or ventricular arrhythmias that meet the ACCF/AHA discontinuation criteria occur, it is necessary to alter the HR, such as with β-blockers, and to investigate and treat the cause of the ventricular arrhythmias, before introducing exercise training. The optimal HR at rest and during exercise for chronic AF has not been clarified, but the ACCF/AHA guidelines recommend a pulse rate of 60–80 beats/min at rest and 90–115 beats/min during moderate-intensity exercise.²³⁰ On the other hand, the RACE II study of HR control in AF found that there was no significant difference in the composite cardiovascular event rate between the strict control group (target resting HR <80 beats/min) and the non-strict control group (target resting HR <110 beats/min).²³¹ Further, there was no significant difference in exercise capacity between the normal HR response group (85–115% of the maximum HR predicted by age) and the excessive HR response group (>115% of the maximum HR).²³² Therefore, the optimal HR at rest and during exercise is unclear at this time.

b. Exercise Prescription

Because AF patients have marked HR elevation in response to exercise load, and the response varies from patient to patient and according to physical condition, setting the exercise intensity according to HR is difficult. For setting exercise intensity, it is preferable to prescribe the AT using CPX, but, if the AT is difficult to detect, exercise capacity (peak V̇O₂) is assessed and the Borg scale may sometimes be used to set exercise intensity. If there is no decline in cardiac function, moderate-intensity load exercise is started. After the introduction of exercise training, blood pressure, HR, and perceived symptoms should be checked, and if the load is judged to be insufficient, the load intensity should be reviewed (Figure 6). For AF patients with concomitant HF, see the Acute/Chronic Heart Failure section (3.0) in this chapter.

6.2 After Device Implantation (Table 38)

Table 38. Recommendations and Levels of Evidence for CR in HF Patients After Device Implantation

	COR	LOE	GOR (MINDS)	LOE (MINDS)
For patients with HF after ICD implantation, it is recommended to provide exercise training and comprehensive disease counseling to improve exercise capacity and QOL	I	A	B	II
For patients with HF after cardiac resynchronization therapy device (CRT-P/ CRT-D) implantation, it is recommended to provide exercise training and comprehensive disease counseling in order to improve exercise capacity and QOL	I	B	B	II
Exercise training should be considered for patients with HF after CRT-P/ CRT-D implantation in order to further improve cardiac function	IIa	B	B	II
For patients with HF after pacemaker, ICD, or CRT-P/CRT-D implantation, taking into account the optimal program setting, exercise training should be considered to improve exercise capacity and QOL	IIa	B	B	II
For HF patients with AF or after pacemaker implantation, CPX should be considered to determine the HR response and optimal program, to assess blood pressure, arrhythmias, and physical activity during exercise, and to evaluate changes in exercise capacity and treatment effects	IIa	B	B	II

Device: cardiac implantable electronic device. AF, atrial fibrillation; COR, class of recommendation; CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; CRT-D, cardiac resynchronization therapy defibrillator; CRT-P, cardiac resynchronization therapy pacemaker; GOR, grade of recommendation; HF, heart failure; HR, heart rate; ICD, implantable cardioverter defibrillator; LOE, level of evidence; QOL, quality of life.

6.2.1 Pacemakers

Patients who are dependent on pacemaker-derived pacing show decreased exercise capacity.²³³ The possible causes include abnormal contraction due to right ventricular pacing, or a poor HR response during exercise (chronotropic incompetence). In particular, patients who are dependent on pacemakers are prone to exercise intolerance.²³⁴ In such cases, the rate-response function is used, but no specific conclusion has been confirmed regarding the improvement of exercise capacity by rate-response alone. The factors determining exercise capacity are considered to be the following: the degree of chronotropic incompetence and its relationship with cardiac function, inadequate rate-response setting during exercise, and skeletal muscle funciton.²³⁵ To improve exercise capacity, adjustment of pacemaker settings should be considered in addition to exercise training.

6.2.2 Implantable Cardioverter Defibrillator

ICD is the most effective and well-established therapy for preventing sudden cardiac death due to fatal tachyarrhythmias and improving life expectancy, regardless of the type of cardiac disease.²³⁶ In addition to implantation for secondary prevention of fatal ventricular arrhythmias, implantation for even primary prevention purposes, such as for patients with HF due to old MI or nonischemic cardiomyopathy with LVEF <35% and NYHA classification II or higher is recommended as “Class I” if nonsustained ventricular tachycardia is present, and recommended as “Class IIa” even if it is not present.²³⁶ Evidence for exercise training in patients with ICD implantation has accumulated, and improvements in exercise capacity,^237,238 vascular endothelial function,²³⁷ QOL,²³⁹ and relief of anxiety and depression²⁴⁰ have been reported. In numerous meta-analyses the exercise training group shows significantly improved exercise capacity compared with the control group.²⁴¹

6.2.3 Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) improves cardiac function by resolving dyssynchrony, resulting in improved perceived symptoms and prognosis. CRT is indicated for patients with moderate to advanced HF despite appropriate medical therapy (primarily NYHA class III–IV, but also NYHA class II in patients with left bundle branch block), and with reduced LVEF (<35%), and wide QRS duration.²³⁶ Although patients with cardiac resynchronization therapy pacemaker (CRT-P)/cardiac resynchronization therapy defibrillator (CRT-D) implantation are good candidates for CR, to date there are few reports on its effectiveness. Conraads et al conducted a RCT of 17 patients with CRT randomized into usual treatment group or exercise group, and reported that peak V̇O₂, maximal workload, LVEF, dyssynchrony, and QOL improved in both groups at 5 months, but the improvement was significantly greater in the exercise group.²⁴² Patwala et al randomly assigned 50 patients to an exercise group or non-exercise group 3 months after CRT-P implantation, with CR for 3 months at 3 times/week, and those with exercise training showed further improvement in NYHA classification and peak V̇O₂.²⁴³ Smolis-Bąk et al divided 52 patients with CRT-D implantation into 2 groups, and after the initial exercise training in the hospital, the group that continued a remotely monitored training program 5 times/week for 8 weeks at home was compared with a control group. After 3–4 months, exercise capacity was significantly improved in the exercise group compared with the control group.²⁴⁴ In a subanalysis of the HF-ACTION study, 224 of 435 patients with CRT-P implantation were assigned to the exercise group. Although peak VO₂ increased in the exercise group, there was no difference in all-cause death, cardiovascular death, or the incidence of rehospitalization.²⁴⁵

6.2.4 Precautions in Exercise Training and Exercise Stress Testing

CPX is also useful for setting up devices and should be performed whenever possible to create an accurate exercise prescription.⁶⁶

a. Adjustment of the Pacing Settings

(1) Rate-response function: If the HR does not rise above the lower rate even during exercise, set the rate-response function. The sensitivity of the sensor, the slope of the HR response, and the upper rate should be set by observing symptoms, such as palpitations. Various sensors, such as accelerometer V̇E, and intracardiac impedance are used. Because accelerometers often do not respond to bicycle ergometer exercise, a treadmill or walking test is recommended. Patients with HF are more likely to have chronotropic incompetence, which is exacerbated by β-blockers and antiarrhythmic drugs. It is controversial whether or not the rate-response function can improve exercise capacity in HF patients.²⁴⁶ In patients with severe chronotropic incompetence, it is recommended to add the rate-response function.

(2) Upper tracking rate: This is the upper limit rate of ventricular pacing following the autologous atrial wave in patients with atrioventricular (AV) block or CRT, and it is a determinant of exercise capacity. It should be set higher in younger patients.

(3) The AV interval: During exercise, biventricular pacing failure may occur in CRT patients due to enhanced AV conduction, which can often be avoided by adjusting the settings of the pacemaker.

b. Adjusting the Tachycardia Detection and Defibrillation Settings

The detection rates of ventricular tachycardia (VT) and ventricular fibrillation (VF) should be checked in advance; the patient should perform exercise at a level to avoid reaching the VT and VF zones. HR of 10–15 beats/min lower than the VT zone should be the upper limit of exercise intensity.⁶⁶ AF patients with high-voltage implanted devices should be monitored for possible HR elevation during exercise.

c. Actual Exercise Therapy for Patients With Implanted Devices

After device implantation, it is considered acceptable to start exercise if HF is under control and high-risk ventricular arrhythmias such as VT and VF are under control, while checking the condition of the wound and lead position, including hematoma and bleeding, and proceeding with checking arrhythmias under ECG monitoring for a time (Table 39).²⁴⁷ Upper limb elevation on the side of the implantation should be limited to 90 degrees of abduction (horizontal elevation) until discharge, but the patient should be instructed to avoid excessive rest, which may limit the range of motion of the shoulder joint.

Table 39. CR Program After Device Implantation (ICD, CRT-P/CRT-D)

	Rest level/shoulder joint elevation on implant side	Device check	Examination	Rehabilitation, disease counseling
Preoperative			Echocardiography, laboratory tests	Information collection
Day of surgery	Indoor/abduction up to 90°	✓	Chest X-ray	Wound check, walking in the room
Postoperative day 1	Same as above		Chest X-ray	Walking in the ward
Postoperative day 2	in the ward/up to 90° abduction			Walking in the ward
Postoperative day 3	Same as above			Aerobic exercise in the rehabilitation room, muscle strength assessment, etc.
Postoperative day 4	Same as above			Aerobic exercise, Strength training using body weight
Postoperative day 5	In-hospital/up to 90° abduction			Same as above Nutritional counseling, medication counseling
Postoperative day 6	Same as above		Chest X-ray, laboratory tests	Same as above, heart failure disease counseling
Postoperative day 7–10/Discharge	In-hospital/discharge, shoulder joint restriction is lifted, but swimming and abduction above 90° should be avoided as much as possible until the outpatient checkup at 1 month, with re-evaluation after confirmation	✓	6-minute walk test, CPX, echocardiography	Same as above, exercise prescription and counseling based on CPX

CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation; CRT-D, cardiac resynchronization therapy defibrillator; CRT-P, cardiac resynchronization therapy pacemaker; ICD, implantable cardioverter defibrillator. (Adapted from Goto Y, 2017²⁴⁷ with modifications.)

7. PH (Table 40)

Table 40. Recommendations and Levels of Evidence for CR in Patients With PH

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Exercise training under supervision should be considered at experienced facilities for pulmonary arterial hypertension and chronic thromboembolic PH patients with less than moderate disease severity who are stable with treatment	IIa	B	B	II
For chronic thromboembolic PH with improved pulmonary hemodynamics after balloon pulmonary angioplasty, exercise training should be considered under supervision at experienced facilities	IIa	B	B	III
Excessive physical activity with accompanying symptoms is not recommended	III (Harm)	C	C2	VI

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; PH, pulmonary hypertension.

Pulmonary hypertension (PH) is defined as a disease that presents with a resting mean pulmonary artery pressure ≥25 mmHg on right heart catheterization²⁴⁸ (>20 mmHg was proposed at the 6th World Symposium on Pulmonary Hypertension in 2018).²⁴⁹ Depending on the pathogenesis, there are 5 groups of PH: Group 1: pulmonary arterial hypertension (PAH), which is mainly caused by vascular remodeling due to overgrowth of endothelial cells and smooth muscle cells in the pulmonary arteries, Group 2: PH due to left heart disease, Group 3: PH due to lung disease and/or hypoxia; Group 4: chronic thromboembolic PH (CTEPH), which is caused by organizing thrombi in the pulmonary arteries; Group 5: PH with unclear and/or multifactorial mechanisms.²⁴⁸ In PAH and CTEPH, as advances in treatment have improved hemodynamics and prognosis;^250–252 rehabilitation aimed at improving exercise capacity and QOL has been recognized as an adjunct to standard treatment.

Recently, in RCTs of rehabilitation for PAH and CTEPH, the 6MWD was significantly prolonged in the rehabilitation group that received 3–15 weeks of exercise training.^253–258 Peak V̇O₂ increased significantly in the rehabilitation group^253,257,258 with an increase of 24%,²⁵⁷ which was comparable to that of respiratory and cardiac diseases. In addition, there were significant improvements in physical activity,²⁵⁴ fatigue,²⁵⁴ and HRQOL scores^253,255,257 in the rehabilitation group. In the 2015 ESC/ERS guidelines, supervised exercise training for physical deconditioning in PAH under pharmacological treatment is classified as Class IIa.²⁴⁸ From the aforementioned RCTs,^253–258 the modality, frequency, intensity, and duration of exercise training have not yet been established. Because residual pulmonary vasculopathy may cause an abnormal pulmonary hemodynamic response during exercise, great care should be taken. As described in Table 40, all exercise training should be performed under close supervision in a facility that is experienced in PH treatment and rehabilitation to avoid excessive exercise. As for Groups 2 and 3 PH, there is little evidence for rehabilitation, and it should be done with caution.

In PAH, chronic hypoperfusion of the skeletal muscles and prolonged physical inactivity can cause morphological changes and dysfunction of the skeletal muscle.^259,260 Exercise training has been shown to increase capillary density and oxidative enzyme activity, which is positively correlated with increased muscular endurance.²⁶¹ The primary mechanism for the improvement of exercise capacity is thought to be improvement of the metabolic capacity of skeletal muscle. In addition, it has been suggested that there may be peripheral endothelial dysfunction in PAH and CTEPH, and thus improvement of peripheral circulation through exercise training is expected to contribute to improved metabolism in skeletal muscle.²⁶² In a prospective study in Japan of patients with CTEPH whose pulmonary hemodynamics had been improved by balloon pulmonary angioplasty, peak V̇O₂ and other parameters increased significantly in the 12-week rehabilitation group compared with the non-rehabilitation group, with no adverse events or worsening of clinical condition.²⁶³ However, syncope, presyncope, and supraventricular tachycardia have been reported as adverse events of exercise training for PH patients.²⁶⁴ In an animal study, it was reported that exercise caused leucocyte infiltration in the right ventricle and remodeling of the pulmonary arteries in rats with severe PH, resulting in decreased survival;²⁶⁵ therefore, long-term safety may be controversial and further study is necessary.

8. Aortic Aneurysm, Aortic Dissection (Table 41)

Table 41. Recommendations and Levels of Evidence for CR in Patients With Aortic Disease

		COR	LOE	GOR (MINDS)	LOE (MINDS)
Preoperative exercise and respiratory rehabilitation with circulatory monitoring is recommended to strengthen cardiopulmonary function and improve postoperative outcomes in patients with abdominal aortic aneurysms		I	A	B	I
After open repair of the aorta, exercise training and respiratory/ swallowing rehabilitation are recommended in order to improve ADL and exercise capacity	Abdominal	I	A	B	II
	Thoracic	I	C	C1	V
In cases of acute aortic dissection for which medical treatment is indicated, ambulation and return to daily life according to a rehabilitation program under HR and blood pressure control should be considered		IIa	C	C1	V

ADL, activities of daily living; COR, class of recommendation; GOR, grade of recommendation; HR, heart rate; LOE, level of evidence.

Compared with the cardiac field, there is less evidence for rehabilitation in the aortic field, and there are no established methods of rehabilitation, effectiveness assessment, or evaluation. Since the advent of endovascular treatment of aortic disease, endovascular treatment has been performed in patients with poor general health such as older patients or frail patients, resulting in a diversification of patients. In the future, aortic rehabilitation is an area where improvement in prognosis and QOL can be expected if appropriate methodologies are established.²⁶⁶

8.1 Before Elective Invasive Treatment

The mean age of patients undergoing aortic repair is higher than that of patients undergoing cardiac surgery, and they more frequently have the complication of COPD.²⁶⁷ Therefore, rehabilitation programs must also take these differences into account. There are several RCTs and systematic reviews that support preoperative exercise training before abdominal aortic aneurysm (AAA) repair.^268–275 However, there are no definitive answers as to the timing, the duration and the intensity of exercise training. Table 42 lists the exclusion and monitoring criteria for exercise training until the repair for AAAs with diameter <50 mm.²⁷² Exercise training for the prevention of aortic aneurysm enlargement is also attracting attention.^275,276 It has been suggested that anti-inflammatory effects and improvement of vascular endothelial cell function as a result of exercise training may inhibit aneurysm expansion.²⁷⁷

Table 42. Example of Exercise Training in Patients With Abdominal Aortic Aneurysm Until the Indication for Invasive Treatment (Aneurysm Diameter <50 mm)

Target	2,000 kcal/week: ≈1 h/day, moderate intensity exercise
Example: 3 times/week	Aerobic exercise 　Treadmill 　Bicycle ergometer 　Stepping stairs 　Rowing 　Cross-training	45 min of aerobic exercise +10 min of resistance exercise
Duration	≥1 year to 3 years (reset in 3 years)
Objective exercise intensity	Start at 60% of HRR, and aim for 80%
Perceived exercise intensity	Borg scale 12–14, as a guide

Exclusion criteria:

(1) Unable or unwilling to complete exercise training for 3 years or a life expectancy <5 years

(2) Unable to participate in an exercise stress test or to exercise consistently because of orthopedic or musculoskeletal problems

(3) Morbid obesity (BMI >39 kg/m²)

(4) Weight gain or loss of 9 kg over the past 3 months

(5) History of severe liver disease (International Normalized Ratio >2, serum albumin <3.0 g/dL, jaundice)

(6) Unstable angina

(7) Uncontrolled AF, defined as mean 24-h HR >85 beats/min, or 24-h maximal ventricular rate >150 beats/min; and uncontrolled ventricular arrhythmias, defined as recurrent ventricular tachycardia >3 PVCs in succession, or 24-h PVC count >20%

(8) Critical aortic stenosis (peak systolic pressure gradient >50 mmHg with an aortic valve orifice area <0.75 cm² in an average-size adult)

(9) Class III/IV HF and/or EF <20%

(10) Active pericarditis or myocarditis

(11) Any embolism within the past 6 months

(12) Thrombophlebitis

(13) Hospitalized because of an infectious disease within the past 3 months

(14) Pulmonary disease with a drop in oxygen saturation with exercise to 90% without oxygen

AF, atrial fibrillation; EF, ejection fraction; HR, heart rate; HRR, heart rate reserve; PVCs, premature ventricular contractions. (Source: based on Myers JN, et al, 2010.²⁷²)

Several RCTs and systematic reviews have shown that preoperative respiratory rehabilitation is effective for COPD, which is the most frequent preoperative complication of aortic repair.^94,278–284 Older age, preoperative dementia or mild cognitive impairment, ASA (American Society of Anesthesiologists) score ≥3, concomitant hypertension and heart disease, prolonged extracorporeal circulation, and massive bleeding have been reported to be associated with postoperative cognitive impairment, postoperative delirium, and impossibility of home discharge.^285,286 Objective assessment of cognitive function using the Mini Mental State Examination (MMSE) should be performed before aortic repair, and an early ambulation program should be also implemented before aortic repair.

8.2 After Invasive Treatment

In recent years, with the spread in the use of clinical pathways, various rehabilitation programs including early ambulation have been formulated and started in the early postoperative period. It is advisable to proceed with early ambulation while checking the progress of medical management: cerebral and spinal nervous system complications, respiratory status, and circulatory dynamics. There is little evidence for recovery-phase CR, compared with what there is for CR for heart disease.

8.2.1 Notes on Program Formulation

a. Intraoperative and Immediate Postoperative Complications

In the acute phase after invasive treatment, refer to the guidelines for rehabilitation in the respective specialty if the patient suffers a neurological disorder such as stroke or spinal cord injury.^287,288

b. Difference Between Endovascular Therapy and Open Repair

Because endovascular treatment is less invasive and requires a shorter period of bed rest than open repair, the postoperative rehabilitation program should take this difference into account.

8.2.2 Early Ambulation After Invasive Treatment

A fast-track rehabilitation and enhanced recovery after surgery (ERAS) is a program for early postoperative ambulation that includes preoperative and intraoperative anesthesia, surgical techniques, and fluid and nutritional management. Once the conditions for ambulation are met (Table 39), ambulation and rehabilitation should begin as early as possible. Early extubation, reduction of respiratory complications, early discharge, and reduction of medical costs can be expected with an early-ambulation program.^289–295

8.2.3 Post-Hospital Discharge

In many cases of postoperative aortic dissection, the dissection remains, so it is common to impose certain restrictions on daily life and physical activity. In other words, aerobic exercise of 3–5 METs for ≈30 min/day (150 min/week) is recommended, and physical strain with exertion should be avoided.²⁹⁶ However, in clinical practice, patients are often subjected to even greater restrictions for fear of recurrence or worsening of the dissection, and few patients are able to return to their pre-dissection life.²⁹⁷ Table 43 shows the guidelines for lifestyle and exercise restrictions after aortic dissection.^296,298

Table 43. Guidelines for Lifestyle and Exercise Restrictions in Patients After Aortic Dissection (Subacute to Chronic)

Exercise

[Recommendations]

• At least 150 min/week of moderate aerobic exercise (3–5 METs for 30 min/day)

• Hiking

• Snorkeling

• Golf

• Tennis

• Cycling

• Weight training 12 RM or lighter

[Not recommended]

• Weightlifting

• Competitive sports

• Exercise using maximal muscle strength

• Weight training 1–11 RM

Daily life

• No limitations in lifestyle (but only for those who completed the appropriate rehabilitation after aortic dissection)

• Sex

• Stepping stairs

• Gardening

• Shopping

• Travel (airplane, carrying a load <20 kg)

RM (repetition maximum): maximum number of repetitions. MET, metabolic equivalent. (Source: based on Chaddha A, et al, 2014,²⁹⁶ Spanos K, et al, 2018.²⁹⁸)

In the recovery phase after aortic aneurysm repair without residual disease, it is recommended to continue exercise training similar to CR after cardiac surgery.²⁹⁹ It is desirable to provide multifaceted support for behavioral change through comprehensive CR by a multidisciplinary team from the acute phase to the recovery phase so that patients can continue lifestyle habits such as smoking cessation, salt reduction, and regular exercise.^{266,300–302}

8.3 Acute Aortic Dissection

8.3.1 Indication

Patients who undergo invasive treatment should undertake the rehabilitation described above. However, patients with uncomplicated acute aortic dissection who are judged not to require invasive treatment in the acute phase require bed rest within 24 h of onset and subsequent CR. In some cases, uncomplicated patients convert to complicated cases as described below during the acute phase (within 14 days of onset) or subacute phase (within 3 months of onset). The CR technicians often notice the change. The current definition of “complicated” includes the following 5 items:^303,304

(1) Rupture, impending rupture

(2) Malperfusion: impaired perfusion to major abdominal branches, lower limbs, spinal nerves, etc.

(3) Persistent or recurrent pain under appropriate medical treatment

(4) Uncontrollable hypertension under appropriate medical treatment

(5) Large aortic diameter (combined with thoracic aortic aneurysm), or rapidly enlarging aortic dissection

The judgment of “uncomplicated” means the patient does not fit the above 5 items; however, cases of (2) to (5) may occur during acute or subacute rehabilitation, and the indications for invasive treatment should be reconsidered.^303,305,306

8.3.2 Methods

A typical rehabilitation schedule for Stanford type B uncomplicated patients in the acute phase is shown in Table 44.³⁰⁷ Hemodynamic management during this phase aims for a HR <60 beats/min and systolic blood pressure ≤120 mmHg at rest, and a HR <100 beats/min and systolic blood pressure ≤140 mmHg during exercise training. There are few reports on rehabilitation in the chronic phase, both for uncomplicated Stanford B dissection and for postoperative acute Stanford A dissection. However, recently the conventional instructions on excessive lifestyle and exercise restrictions have been slightly relaxed, and there are more reports supporting active exercise training and return to unrestricted daily life.²⁹⁸ Table 43 shows a guide for lifestyle and exercise restrictions after aortic dissection.^296,298

Table 44. An Example of Early Rehabilitation Program After Stanford Type B Uncomplicated Acute Aortic Dissection

	Rest level	Face washing	Urination/ defecation	Oral intake	Bathing	Checking vital signs	CT inspection
Day of onset	Bed rest	On the bed (with assistance)	On the bed (urinary catheter)	None	Bed bath (with assistance)	Every 2 h	✓
Day 1	Self sitting	On the bed (without assistance)		With assistance
Day 2	Walking is allowed around the bed (walking to the lavatory is allowed)	Lavatory in the room	Lavatory in the room			Every 3 h
Day 3				Without assistance	Bed bath (without assistance)	Every 4 h	✓ (if symptoms persist, or conditions worsen)
Day 4	Walking freely within the ward	Lavatory in the ward	Lavatory in the ward
Day 5	Walking freely in the ward
Day 6
Day 7	Walking freely within the facility				Taking a shower (without assistance)		✓

(Source: based on Niino T, et al, 2009.³⁰⁷)

9. Peripheral Arterial Diseases (Table 45)

Table 45. Recommendations and Levels of Evidence for Exercise Training in Patients With Peripheral Arterial Disease and Claudication

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Supervised exercise training (for at least 3 months) is recommended	I	A	A	I
Prior to revascularization, supervised treadmill exercise training is recommended	I	B	B	I
After revascularization, exercise training is recommended	I	A	A	I
In patients who have difficulty with supervised exercise training, home-based exercise training (>3 months) should be considered	IIa	A	A	II
Ergometer exercises of the upper or lower extremities under supervision should be considered	IIa	A	B	II

COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence.

9.1 Comprehensive CR Program Based on Exercise Training

Exercise training is the basic and crucial treatment for peripheral arterial disease (PAD) other than critical limb ischemia (CLI). The majority of deaths in patients with PAD are not due to gangrene of the lower extremities, but rather to MI and stroke,^308–311 which may be due to reduced exercise capacity and daily activity (Figure 7).³¹² The prognosis of asymptomatic PAD without symptoms of claudication is also reported to be poor, suggesting the need for early diagnosis and intervention. In CLI, endovascular treatment or bypass surgery should be performed first to save the limb (Figure 8).^313–316 After that, it is reported that the amount of daily activity does not increase much unless exercise training is well supervised.³¹⁷ In order to complete the treatment of CLI, it is necessary not only to relieve tissue ischemia by revascularization but also to continuously improve exercise capacity and vascular function by exercise training. In addition, a comprehensive CR program includes complete smoking cessation, blood pressure control with antihypertensive medication and salt reduction for patients with hypertension, glycemic control for diabetes mellitus, and appropriate medication such as antiplatelet agents and statins.

Figure 7.

Negative effects of reduced walking habit in patients with peripheral arterial disease (PAD). Decreased exercise capacity may be a cause of increased cardiac and cerebrovascular events in patients with PAD with intermittent claudication. It has been reported that the peak V̇O₂ of PAD patients with intermittent claudication is ≈50% of that of normal subjects of the same age. Such a low exercise capacity status inevitably leads to decreased physical activity in daily life, which contributes to skeletal muscle deficiency and visceral obesity, leading to further development of systemic atherosclerosis through insulin resistance and other factors. As a result, cardiac and cerebrovascular events increase. HDL, high-density lipoprotein; PAD, peripheral arterial disease; TG, triglyceride. (Adapted from Yasu T, 2012³¹² with modifications.)

Figure 8.

Treatment algorithm for peripheral arterial disease. In mild to moderate cases of Fontaine classification I and II, supervised exercise training and administration of antiplatelet agents are conducted. If there is no improvement in symptoms after ≈3 months, revascularization should be encouraged. In patients with severe ischemia (i.e., CLI) of Fontaine classification III or IV, after detailed local diagnosis by CT, MRI, or echocardiography, revascularization therapy should be selected, followed by exercise instruction. Contraindications to exercise training are CLI complicated by infection, acute arterial occlusion (embolism, thrombosis), and serious complications (unstable angina, congestive heart failure, severe aortic stenosis, infection, etc.). CAD, coronary artery disease; CLI, critical limb ischemia; CVD, cardiovascular disease. (Source: based on Gerhard-Herman MD, et al, 2017,³¹³ McDermott MM, 2017,³¹⁴ Treat-Jacobson D, et al, 2019,³¹⁵ Japanese Circulation Society, 2016.³¹⁶)

9.2 Indications and Contraindications

Exercise training is indicated in patients with chronic peripheral arterial stenosis, with or without intermittent claudication. The Fontaine and Rutherford classifications are frequently used to classify the severity of the disease based on clinical symptoms (Table 46).³¹⁷ In cases of severe lower extremity ischemia with ulceration or gangrene, it should be kept to mild exercise with loading in the absence of infection. Exercise training is contraindicated in acute arterial occlusion (embolism or thrombosis) and in CLI with infection.

Table 46. Classification and Treatment of Peripheral Arterial Disease Based on Symptoms

Fontaine classification	Rutherford classification	Treatment modality
I: Asymptomatic	0: Asymptomatic	Atherosclerosis risk management, antiplatelet agents, exercise training, foot care
IIa: Mild claudication	1: Mild claudication	Atherosclerosis risk management, exercise training, antiplatelet agents, foot care
IIb: Moderate to severe claudication	2: Moderate claudication	Exercise training, antiplatelet agents, revascularization, arteriosclerosis risk management
	3: Severe claudication
III: Pain at rest	4: Pain at rest	Revascularization, antiplatelet agents, exercise training, foot care, arteriosclerosis risk management
IV: Ulceration, gangrene	5: Minor tissue loss	Revascularization with wound care, antiplatelet agents, decompression and exercise training (if there is no infection after revascularization), arteriosclerosis risk management
	6: Major tissue loss

(Source: based on Norgren L, et al, 2007.³¹⁷)

9.3 Preparation

9.3.1 Medical Check

The risk factors for PAD include diabetes mellitus, smoking, hypertension, dyslipidemia, old age, and renal failure. Because of the peripheral neuropathy in diabetic patients, and very older patients and chronic renal failure, patients do not walk, PAD progresses without perceived symptoms, and patients will not come as outpatients until they develop CLI with ulceration and necrosis. There is a possibility that 15% of patients diagnosed with spinal canal stenosis may have PAD, which requires attention. In the examination, palpation of the inguinal femoral artery, popliteal artery, dorsal foot artery, and posterior tibial artery should be performed; skin temperature and the presence of skin lesions should always be checked.

9.3.2 Exercise Stress Test

PAD is often associated with other atherosclerotic diseases; the patient should be monitored for ischemic symptoms in vital organs during the initial exercise stress test. It is necessary to confirm that there are no anginal symptoms, no ECG changes, and no arrhythmias during the exercise stress test while monitoring blood pressure and ECG. To evaluate the severity of the disease, walking distance measurement using the Gardner protocol treadmill and ankle joint blood pressure measurement before and after exercise are useful, and can be used as an index of claudication symptoms before and after treatment.^{313–316,318}

9.4 Protocols

9.4.1 Supervised and Home-Based Exercise Training

Supervision for exercise training is recommended for symptomatic PAD (Class I, Level of Evidence A).^312,313,319 In a meta-analysis of exercise training for PAD patients with intermittent claudication, predominantly supervised exercise training (30 min of track or treadmill walking 3 days/week) increased the maximum walking distance by 260 m compared with usual care.³¹⁷ In other meta-analyses, supervised exercise training was associated with a maximum walking distance of approximately 150 m longer at 3 months than home-based exercise training, suggesting that supervised exercise training is important.^312,313,319 In a recent meta-analysis of 25 RCTs,³¹⁴ supervised exercise training increased the maximum walking distance by 180 m in the treadmill test compared with the control group. In a RCT of patients with only Fontaine II iliac artery lesions, supervised exercise training significantly prolonged the maximum walking distance compared with stenting, suggesting that it is important to prioritize supervised exercise training even in patients with iliac artery lesions.³²⁰ However, in reality, supervised exercise training is not feasible for various reasons, including the difficulty of frequent hospital visits. Therefore, it is necessary to start unsupervised walking exercise (home-based exercise training with oral medication: Class IIa Level of Evidence A)^{312,313,319,321} as early as possible, and to support the establishment of an exercise habit by checking the number of steps with a pedometer and keeping an exercise diary.

9.4.2 Exercise Training in Practice

In order to learn correct exercise training and to educate patients, if possible supervised exercise training should be performed for the first time, followed by a transition to home-based exercise training. Even after the patient is able to walk after revascularization, the same instructions should be provided for exercise training to improve the prognosis (Figure 8). The type of exercise (treadmill, track walking, ergometer), frequency (3–5 days/week), intensity (speed and incline), and duration (30–45 min) are determined by the results of the exercise stress test for each patient. As symptoms improve, the exercise prescription should be changed accordingly. Exercise should be continued at least 3 times/week for at least 12 weeks.

9.4.3 Types of Exercise

Treadmill, track walking, and water walking are recommended for PAD. Exercise training is programmed in the following order: (1) warm-up, (2) walking exercise, and (3) cool-down. Treadmills and bicycle ergometers are easy to use because the intensity of exercise can be adjusted, but walking on a track with a pacemaker can also be used.

9.4.4 Exercise Intensity, Duration, and Interval

The recommended settings for treadmill walking are to start at an incline of 12% and a speed of 2.4 km/h and walk until lower extremity pain occurs at a submaximal load of about “quite painful” (Borg scale 15–17)^322–324 (Table 47). If the patient can walk for >10 min at this intensity, then the speed should be increased to 3.2 km/h or the incline should be increased. Stop walking when the pain becomes “very painful” during walking. Take a break (≈1–5 min) until the pain disappears, and perform the same exercise again until moderate claudication appears. This should be repeated for at least 30 min in the first training session, and extended by 5 min for each training session, up to a maximum of 60 min. Exercise is performed once or twice daily, at least 3 times/week (5 days/week or more if possible), for at least 3 months. In addition, “continuous walking training at home” in between supervised exercise training should be actively performed.

Table 47. Supervised Exercise Training Program for Patients With Peripheral Arterial Disease

1. 10 min of stretching as a preparatory exercise

2. Initial exercise intensity should be set based on the maximum walking time of the Gardner protocol treadmill, and the treadmill walking exercise should be performed at a speed that causes claudication in 3–5 min. The patient should be allowed to walk continuously until reaching the Borg scale 15–17 of “very hard”

3. After a break of a few minutes, perform treadmill walking exercise according to No. 2 above

4. Continue this interval walking training for ≈30–60 min

5. Finish the exercise with a cool-down exercise

9.4.5 Combination With Drug Therapy

Cilostazol (phosphodiesterase III inhibitor) significantly prolonged the maximum walking distance in a study of PAD patients with intermittent claudication, and it is recommended as a first-line treatment in the guidelines of TASC II,³¹⁷ ACC/AHA,³¹³ and the Japanese Circulation Society³¹⁶ (Class I, Level of Evidence A) (Figure 8). In cases where the use of cilostazol is difficult, such as when complicated with HF, salpogrelate (serotonin receptor antagonist), prostaglandins, and eicosapentaenoic acid are alternatively selected. Antiplatelet agents (aspirin, clopidogrel) are also recommended as Class I because they are expected to inhibit cardiovascular events, although they do not improve claudication symptoms. Statins are now recommended^313,325 as Class I, with evidence that they improve prognosis and claudication symptoms. It has been reported that intravenous heparin and continued exercise training program can safely reduce claudication symptoms and increase the maximum walking distance.³²⁶

9.4.6 After Revascularization

Exercise training instruction after revascularization is important in terms of secondary prevention and the prevention of cardiovascular events, and it should be started the day after surgery if there are no complications^312,313,316 (Figure 8). However, a prospective observational study of PAD patients who underwent Fontaine II-degree endovascular therapy found that although the ankle–brachial index and maximum walking distance improved significantly after endovascular therapy, the average daily step count and physical activity did not improve afterwards.³²⁷ Therefore, comprehensive CR with multidisciplinary interventions is necessary to increase the number of participants and ultimately contribute to the reduction of healthcare costs.

V. CR for Special Patient Groups

1. Older Patients With Heart Disease (Table 48)

Table 48. Recommendations and Levels of Evidence for CR in Older Patients With Heart Disease

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In older patients with CAD, aerobic exercise and resistance training are recommended to be performed concomitantly to improve exercise capacity, muscle strength, and QOL	I	A	A	II
In older patients with CAD, aerobic exercise is recommended to correct coronary risk factors	I	A	A	II
In older patients with HF, exercise training is recommended to improve QOL	I	A	B	II
In older patients with HF, a combined exercise regimen consisting of aerobic exercise, resistance training, balance training, and flexibility exercises should be considered to improve exercise capacity and physical function	IIa	A	B	II
In older heart disease patients with combined frailty and sarcopenia, exercise and nutritional therapy should be combined to improve exercise capacity and muscle strength	IIa	B	B	II
Patient education may be considered to improve the prognosis of older patients with HF	IIb	B	C1	II
Resistance training may be considered to improve physical function in very old patients with heart disease	IIb	C	C1	VI

CAD, coronary artery disease; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; QOL, quality of life.

1.1 Characteristics of Older Patients With Cardiac Disease and Precautions During Exercise Training

The ACCF/AHA “guidelines for the secondary prevention of CAD in patients aged 75 years and older” recommend that treatment of coronary risk factors should follow the same principles as in the general adult population.³²⁸ On the other hand, the provision of medical care to older people can be difficult because of the wide variation in disease symptoms and response to treatment due to physical changes associated with aging, the fact that they may suffer from multiple chronic diseases, and the fact that medical treatment guidelines for older people are not well established.³²⁹ In addition, because the progressive rate of aging varies among individuals and the degree of the effect on physical, mental, and social functioning varies, it is important to consider the effect not only on health problems such as cardiac diseases and complications but also on the psychological and social aspects (biopsychosocial model) in older patients with cardiac diseases.³³⁰ Together with the patient, family, and caregivers, it is necessary to determine an individualized treatment plan based on the characteristics of the older patient (Figure 9).³³⁰

Figure 9.

Decision-making process for older patients with heart disease. *Polypharmacy: Prescribing more drugs or medications than needed, resulting in increased risk of adverse events, medication errors, and poor medication adherence. AF, atrial fibrillation; COPD, chronic obstructive pulmonary disease.

Although there is disagreement on the effects of cardiac rehabilitation (CR) on the prognosis and exercise capacity in older patients with cardiac disease,^331–336 there is growing evidence that CR can improve quality of life (QOL).^336,337 Cardiac disease in older patients is characterized by a number of comorbidities, which may define their prognosis and prevent them from participating in CR due to the need to be very careful. There are specific cautions for older patients during exercise training.

1.1.1 Complications of Frailty and Sarcopenia

Complications of frailty and reduced gait speed are factors that worsen the prognosis.³³⁸ A complex exercise regimen for older heart failure (HF) patients¹⁷¹ and patients after cardiac surgery,³³⁹ consisting of aerobic exercise, resistance training, balance training, and flexibility exercises has been reported to improve frailty and the Short Physical Performance Battery. However, there is insufficient evidence for comprehensive CR for older cardiac patients with frailty.

Although several meta-analyses have shown that resistance training for sarcopenia improves muscle mass, muscle strength, and gait speed,^340,341 there are no reports examining the effects of CR in older cardiac patients with sarcopenia, and thus more evidence is needed.

1.1.2 Very Old Patients

There are no reports examining the effects of CR in very old patients with cardiac diseases aged ≥90 years. However, in a study examining the effects of exercise training on older patients with an average age of 87 years in an institution, it was reported that resistance training significantly improved knee extensor strength and gait speed.³⁴² Furthermore, an exercise program combining resistance training with aerobic exercise and balance training has been reported to improve physical function and reduce the risk of falling.³⁴³ Although there have been no reports of serious adverse events caused by exercise training in very old patients, there have been cases in which exercise was discontinued due to muscle pain or knee pain. As the number of complications increases with age, it is necessary to pay close attention to physical condition management.

2. Pediatric Patients With Heart Disease

2.1 Congenital Heart Disease (Table 49)

Table 49. Recommendations and Levels of Evidence for Exercise Training in Pediatric Patients With CHD

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Exercise training should be considered in order to increase exercise capacity and improve QOL	IIa	B	B	II

Note: When implementing exercise training, it is advisable to take into account disease specificity. CHD, congenital heart disease; COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence; QOL, quality of life.

2.1.1 Current Status of Survival and Rehabilitation

Over the past few decades, there has been remarkable progress in improving the surgical outcomes and survival rates of patients with congenital heart disease (CHD), and the number of CHD patients reaching adulthood has been increasing.^344–347 The survival rate of CHD patients up to age 16 years has increased from 62.4% in 1971–1989 to 86.9% in 1990–2011.³⁴⁷ In Japan, the number of adult CHD (ACHD) patients exceeded 400,000 in 2007, which is already higher than the number of pediatric CHD patients, and the number is reported to increase by 9,000 cases per year.³⁴⁵ In ACHD patients, regular exercise training is important to improve physical fitness and QOL.

At present, there are no clear guidelines on exercise training and other rehabilitation for pediatric CHD patients, so decisions must be made on a case-by-case basis, taking into account the disease, severity, and timing (age). In addition, there is little evidence on the rehabilitation and permission of exercise for CHD patients younger than 10 years, so the exercise prescription should be made with caution, especially for patients younger than 6 years, for whom exercise testing is not possible.

2.1.2 Objectives of Exercise Training

With the exception of those who do not have impaired exercise capacity preoperatively or postoperatively, children with CHD have obvious physical weakness and some limitations in school and social life. Exercise habits and a healthy and active lifestyle during growth are important not only for improving exercise capacity, but also for cardiovascular and musculoskeletal development, mental development, and the prevention of metabolic syndrome.³⁴⁸ The purpose of exercise training for CHD in children with reduced exercise capacity and abnormal cardiovascular responses to exercise is to: (1) improve exercise capacity, safety, and QOL, (2) improve active social participation and productive role, and (3) correct future coronary risk factors such as hypertension, diabetes mellitus, and dyslipidemia by developing an exercise habit.

2.1.3 Assessment of Exercise Capacity and Exercise Prescription

Cardiopulmonary exercise testing (CPX) is commonly used to assess exercise capacity. Exercise intensity is prescribed based on disease and patient specificity, but particular attention should be paid to the risk and history of obvious ventricular dysfunction and arrhythmias. Based on previous reports,^349–357 a common exercise protocol for patients with CHD is a 10-min warm-up or stretch, 40 min of aerobic exercise, and a 10-min cool-down. The exercise intensity should be, as a guide, 60–70% of heart rate reserve (HRR), 65–80% of maximum HR, HR of the anaerobic threshold (AT), and <80% of peak V̇O₂. However, the intensity of exercise should vary according to the severity of the heart disease. In general, the exercise frequency prescription is 2–3 times/week, for ≈60 min each time, and for ≈12 weeks.

2.1.4 Effectiveness of Exercise Training

Exercise training has also been shown to increase peak V̇O₂.^349,353,356 In a meta-analysis, the improvement of peak V̇O₂ after exercise training was 3.68 mL/min/kg (95% confidence interval 1.58 to 5.78) in weighted mean difference.³⁴⁹ Peripheral effects accounted for a large part of the mechanism of increased exercise capacity,³⁵¹ but a significant increase in stroke volume has been noted.³⁵⁸ In addition, there are reports of improved HR response,³⁵² improved respiratory function,^354,355 and other effects such as increased muscle strength,³⁵⁹ and improved QOL.^349,357

3. Heart Failure Patients Under Intravenous Inotropic Drugs (Table 50)

Table 50. Recommendations and Levels of Evidence for CR in Patients With HF Receiving Intravenous Inotropic Drugs

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In hemodynamically stable patients, CR may be considered to prevent or improve the progression of deconditioning	IIb	C	C1	V

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

3.1 Evidence

In principle, exercise training is contraindicated in patients with acute or advanced HF who are hemodynamically unstable or have symptoms such as dyspnea even at rest. However, in recent years, many institutions have started to offer exercise training to patients with advanced HF who are receiving intravenous inotropic drugs, as long as they are hemodynamically stable and have no symptoms at rest.

Although there are no randomized controlled trials (RCTs) that have examined the effects of CR in a large number of patients with HF receiving intravenous inotropic drugs, there are many reports that low-intensity rehabilitation can be performed safely.^360–367

Arena et al reported that a patient on the waiting list for heart transplantation receiving intravenous inotropic drugs underwent 246 sessions of aerobic exercise for 180 h over a period of a little more than 1 year, and exercise capacity improved by >30%, with only one adverse event being a hypotensive episode.³⁶¹ Forestieri et al reported that in patients on the waiting list for heart transplantation receiving intravenous inotropic drugs, the 6-minute walk distance (6MWD) was significantly improved in the bicycle ergometer exercise group (7 patients) compared with the control group (11 patients).³⁶⁷

3.2 Adaptation

In patients with HF receiving intravenous inotropic drugs, CR is indicated in the same way as for normal patients with chronic HF: no contraindications to exercise training (Table 28), hemodynamically controlled and stable (i.e., no worsening of subjective symptoms of HF (dyspnea, fatigue, etc.) or physical findings (edema, pulmonary congestion, etc.) in at least the recent 3 days, and no excessive fluid retention or dehydration). In addition, the patient must be independent in terms of activities of daily living (ADL) before admission, and must have an understanding and willingness to undergo CR.

In practice, the main indications are for patients who are expected to have difficulty with early withdrawal of intravenous inotropic drugs and for patients on the waiting list for heart transplantation who are dependent on intravenous inotropic drugs. In order to avoid starting CR before reaching a stable stage and hindering recovery in HF, or rushing to stage up and causing HF to worsen again, it is critical that the timing of starting CR and staging up, as well as the pathology, are thoroughly understood and careful judgment is made by cardiologists.

3.3 Risks and Discontinuation Criteria

Patients with HF receiving intravenous inotropic drugs are considered to be at higher risk than usual of worsening HF and arrhythmia, even during the stable period. Therefore, to avoid overloaded rehabilitation, the criteria for stopping rehabilitation should be set in advance, and rehabilitation should be discontinued when those criteria are met, such as shortness of breath or fatigue with a Borg scale of ≥14. Although it is difficult to apply the same discontinuation criteria to all patients with HF, it is possible to safely perform rehabilitation by making modifications to the basic discontinuation criteria (Table 51) according to the patient’s medical condition.

Table 51. Terminating Criteria for the Rehabilitation Motion in HF Patients Receiving Intravenous Inotropic Drugs (An Example From the National Cerebral and Cardiovascular Center)

1) Perceived symptoms: shortness of breath, fatigue (Borg scale ≥14), consciousness disturbance, fainting, unsteady walking, cold sweat, etc.

2) Heart rate (in sinus rhythm): <50 beats/min or ≥130 beats/min, or an increase of ≥30 beats/min from rest

3) Systolic blood pressure: <70 mmHg, or decrease of ≥20 mmHg from rest

4) Appearance of new arrhythmia

5) Percutaneous arterial oxygen saturation (SpO2): <90%

6) Occurrence of intravenous line complication

HF, heart failure.

4. After Ventricular Assist Device (VAD) Implantation, After Cardiac Transplantation

4.1 After VAD Implantation (Table 52)

Table 52. Recommendations and Levels of Evidence for CR in Patients After VAD Implantation

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to implement a comprehensive rehabilitation program for all patients who are eligible to participate	I	B	B	III
Exercise training combining aerobic exercise and resistance training is recommended	I	C	B	III
It is recommended to implement a CR program for patients with VAD in facilities with expertise in managing VAD patients	I	C	C1	IVb
Exercise training based on exercise prescription by RPE or CPX should be considered	IIa	C	B	III
Periodic 6-minute walk test and CPX should be considered to evaluate exercise capacity and prescribe the appropriate exercise training program	IIa	C	B	III

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; RPE, rating of perceived exertion; VAD, ventricular assist device.

4.1.1 Objectives of CR

In patients with advanced HF who are eligible for VAD implantation, it is quite common that their muscle strength and nutritional status are impaired, and their exercise capacity is often severely impaired. Although VAD improves patients’ hemodynamic parameters, it takes time before their exercise capacity improves. Even if the purpose of VAD is “bridge to transplantation”, the waiting time before heart transplantation is quite long and more than several years in Japan, so there is a high need for CR to improve ADL, exercise capacity, and QOL during this period.^368,369 Regarding the safety and efficacy of CR after VAD implantation, there are many positive reports,^370–376 but most include only a small number of patients; a meta-analysis showed improvements in exercise capacity and QOL.^377,378 The purpose of CR for patients after VAD implantation is shown in Table 53.

Table 53. Purposes of CR in Patients With a VAD

Phase	Purpose and significance
Acute phase	• Improvement of deconditioning due to prolonged rest and muscle disuse
	• Acquisition of ADL that enable patients to live at home
	• Establishment of safe daily activities with a VAD
Early recovery phase	• Improvement of exercise capacity, mental health and QOL for social return with a long-term VAD
	• Education and support for the safe management of the VAD, driveline care, and anticoagulation management
	• Education and support for VAD-related complications and their prevention, recognition and management
Late recovery phase – maintenance phase	In addition to the content of the early recovery phase
	• Education and support (including caregivers) on safety management of VAD devices
	• [For patients waiting for heart transplant] Education and support in preparation for heart transplant surgery

ADL, activities of daily living; CR, cardiac rehabilitation; QOL, quality of life; VAD, ventricular assist device.

4.2 After Cardiac Transplantation (Table 54)

Table 54. Recommendations and Levels of Evidence for CR in Patients After Cardiac Transplantation

	COR	LOE	GOR (MINDS)	LOE (MINDS)
A comprehensive rehabilitation program should be implemented for all eligible patients	I	A	A	I
In the management of patients after cardiac transplantation, it is important to use a facility with appropriate expertise	IIa	B	B	II
Exercise training that combines aerobic exercise and resistance training should be considered	IIa	B	B	II
Exercise training based on exercise prescription by RPE or CPX should be considered	IIa	C	C1	III
6-minute walk test and CPX should be performed periodically to evaluate exercise capacity and for the appropriate exercise prescription	IIa	C	C1	III

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence; RPE, rating of perceived exertion.

4.2.1 Physiology of the Transplanted Heart (Denervated Heart)

In the denervated heart,^379–381 HR and cardiac contractility before and after exercise are controlled by adrenaline secreted by the adrenal gland, so that there is little increase in HR during exercise, but rather it is increased by adrenal-derived catecholamines after the end of exercise, followed by a slow decrease in HR. In heart transplant patients, the HR at 1 min after the end of exercise is often higher than the HR at the time of maximal exercise loading. Because of denervation, the increase in cardiac output in the early phase of exercise in transplanted hearts is influenced by decreased peripheral vascular resistance and increased venous perfusion by skeletal muscle pumps. However, the increase in cardiac output by this mechanism is up to 20%, and a further increase must wait for an increase in adrenaline in the blood. Furthermore, chest pain during myocardial ischemia is no longer present.

4.2.2 Efficacy of Exercise Training

Reports on the effects of exercise training in heart transplant recipients have appeared since the 1980s,³⁸² and in 1999, an RCT of heart transplant recipients assigned to an exercise group or a control group was reported.³⁸³ In that report, early post-transplant exercise training significantly improved exercise capacity beyond spontaneous recovery. In 2005, it was reported that there was no difference in the effect of exercise training between men and women.³⁸⁴ Therefore, exercise training is useful in improving exercise capacity and QOL in patients after heart transplantation, and CR is recommended for all heart transplant recipients who are able to participate.^382–384

4.2.3 Pediatric Patients After Heart Transplantation (Table 55)

Table 55. Recommendations and Levels of Evidence for Exercise Training in Pediatric Patients After Heart Transplantation

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Exercise training may be considered	IIb	C	B	V

COR, class of recommendation; GOR, grade of recommendation; LOE, level of evidence.

In recent years the number of pediatric heart transplant recipients in Japan has been gradually increasing. Most of the candidates have dilated or restrictive cardiomyopathy. It has been reported that the exercise capacity of children after heart transplantation is severely inferior to that of healthy children.^385–387 The cause of the decreased exercise capacity may be multifactorial, but the main cause is chronotropic incompetence due to surgical sympathetic disconnection at the time of heart transplantation. In addition, there are other causes, such as increased pulmonary vascular resistance and increased pulmonary vascular resistance. It has been reported that 16 of 29 patients with sympathetic reinnervation by positron emission tomography during follow-up after heart transplantation showed an elevated HR response during exercise.³⁸⁸

Although the effectiveness of rehabilitation after heart transplantation has been reported in adults,^383,387 Hsu et al reported improved QOL after exercise training in 45 heart-transplant children.³⁸⁹ Their protocol consisted of a 10-min warm-up, exercise intensity of 50–80% of peak V̇O₂, 25–30 min of walking on a bicycle ergometer or treadmill, and a 10-min cool-down. Exercise training improved peak V̇O₂ by an average of 24% in 2–3 months. It has been reported that resistance training increases skeletal muscle mass and strength, and high-intensity interval training has been shown to improve exercise capacity, health awareness, anxiety, and depression.³⁹⁰

5. Cancer Patients With Cardiac Diseases

5.1 Overview of Cardio-Oncology Rehabilitation

“Cardio-oncology rehabilitation” (CORE) is a new concept proposed by the AHA and is being studied with the goal of becoming the standard of care in the future.^391,392 Adding CR to cancer rehabilitation is expected to improve cardiopulmonary endurance in cancer survivors^393–396 and reduce the risk of cardiovascular disease (CVD).^397,398

The so-called “cancer rehab” is medical care that diagnoses and treats physical, cognitive, and psychological disorders in order to improve the independence and QOL of cancer patients,³⁹³ whereas CR is comprehensive and a long-term medical care that includes medical examinations, an exercise prescription, cardiovascular risk factor (CVRF) reduction, education and counseling, and lifestyle improvement for the purpose of CVD treatment and recurrence prevention.³⁹⁴

5.2 Practice of CORE

5.2.1 Target Diseases

Based on the American Society of Clinical Oncology Practice Guideline,³⁹⁹ the AHA has identified high-risk cancer treatments (e.g., high-dose radiation therapy, high-dose anticancer drugs, or combination of anticancer drugs and molecularly targeted drugs) and high-risk patients (e.g., history of cardiac disease or multiple CVRFs) as the primary targets for CORE.^391,400

(1) High-dose anthracycline (doxorubicin equivalent ≥250 mg/m²), high-dose radiotherapy (≥30Gy and treatment field including the heart), or combination of low-dose anthracycline and low-dose radiotherapy.

(2) Presence of risk factors, such as use of low-dose anthracycline or trastuzumab alone, and CVRF (≥2 of smoking, hypertension, diabetes, obesity, or dyslipidemia), age ≥60 years, or cardiac dysfunction (history of myocardial infarction (MI), reduced left ventricular ejection fraction, moderate valvular disease).

(3) Low-dose anthracycline followed by trastuzumab combination therapy.

This should be referred to as the starting point for introducing CORE, and the final decision should be made by a cardiologist or oncologist, taking into account the type and stage of cancer, physical function, and comorbidities.

5.2.2 Implementation Algorithm

Figure 10 shows an overview of CORE.³⁹¹ Referral to CORE is based on identification of high-risk treatment, high-risk patient, and comprehensive assessment of clinical symptoms and comorbidities. At the start of CORE, safety is first assessed by CPX and the 6-minute walk test. For safety issues related to cancer treatment (e.g., frailty, neuromusculoskeletal disorders, osteoporosis, cognitive decline), the exercise plan is optimized for each patient as part of “cancer rehab” (e.g., physical therapy, occupational therapy, speech therapy). As for the collaboration between oncologists and cardiologists, it is important to consider the circumstances of each institution and region, such as whether it should be implemented as team medical care at a cancer center or as community medical care collaboration based on family physicians.

Figure 10.

Overview of cardio-oncology rehabilitation (CORE). CPX, cardiopulmonary exercise testing; CVD, cardiovascular disease. (Adapted from Gilchrist SC, et al, 2019³⁹¹ with modifications.)

VI. Nutrition and Diet Therapy

1. Nutritional Assessment Methods (Table 56)

Table 56. Recommendations and Levels of Evidence for Intervention/Counseling for Nutritional Assessment Methods and Lifestyle-Related Disease in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to provide nutritional counseling using anthropometry/body measurements and nutritional assessment tools	I	C	C1	III
A combination of nutrition education, diet modification and exercise training is recommended for weight loss	I	A	A	I
Instruction of a low-sodium diet of ≈6 g/day should be considered	IIa	C	B	II

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

Because each nutritional assessment method has its own characteristics, it is important to implement in combination with multiple assessments.⁴⁰¹

1.1 Anthropometry/Body Measurements

Body weight (BW) as a nutritional assessment is among the most convenient of the indices because it is not invasive to measure.⁴⁰¹ However, because changes in fluid balance complicate the assessment of BW in patients with heart disease, it should be measured before meals, and the body mass index (BMI), rate of change in BW, and body composition should be measured in the absence of edema. Nutritional assessment using physical measurements includes the following:

(1) BMI = weight (kg) / height (m)²

(2) Standard body weight ratio: %IBW (% ideal body weight) = present weight (kg) / IBW ([height (m)²] × 22) × 100

(3) Weight change rate: % LBW (% loss of body weight)= (normal weight − weight at measurement) / normal weight × 100

(4) Body composition measurement

Bioelectrical impedance analysis is a method of analyzing body components (muscle mass, fat mass, and water content) by applying a weak electric current through the body to obtain resistance values.⁴⁰¹ Compared with dual-energy X-ray absorptiometry, there is no radiation exposure and less inter-measurement error. According to the Asian Sarcopenia Working Group (AWGS) sarcopenia diagnostic criteria (2019), sarcopenia should be evaluated by skeletal muscle index (SMI, ≤7.0 kg/m² for men and ≤5.7 kg/m² for women), gait speed (<1.0 m/s), and grip strength (<28 kg for men, <18 kg for women).⁴⁸

(5) Grip strength

Grip strength can be easily measured, and its increase is an indicator of improvement in muscle function. When nutritional status improves, muscle function improves before muscle mass, making it an excellent nutritional assessment method.

1.2 Blood Test Data

Blood albumin, which is the nutritional assessment of visceral protein stores, reflects the severity of disease, such as inflammation and dilution of blood due to increased fluid volume; alone it is not an indicator of nutritional status.⁴⁰¹

1.3 Nutritional Assessment Tools

Nutritional assessment tools include the following: (1) Subjective Global Assessment (SGA),⁴⁰² (2) Controlling Nutritional Status (CONUT),⁴⁰³ (3) Geriatric Nutritional Index (GNRI),⁴⁰⁴ (4) Mini Nutritional Assessment-Short Form (MNA^®-SF) and Mini Nutritional Assessment (MNA^®),^405–407 and (5) Global Leadership Initiative on Malnutrition (GLIM) criteria.⁴⁰⁸ Each tool has its own features and should be used with an understanding of the advantages and disadvantages.

1.3.1 CONUT

Albumin, total lymphocyte count, and total cholesterol are scored, and the sum of these scores is the CONUT value (Table 57).⁴⁰³ Because it is frequently used as a general biochemical test, CONUT is suitable for use in many patients, including inpatients and outpatients. However, because there is no information on physical findings, it should be judged in combination with clinical information.

Table 57. Nutritional Assessment by CONUT

Parameter	Value	Score
Serum albumin (mg/dL)	≥3.50	0
	3.49–3.00	2
	2.99–2.50	4
	<2.50	6
Total lymphocytes (/μL)	≥1,600	0
	1,599–1,200	1
	1,199–800	2
	<800	3
Total cholesterol (mg/dL)	≥180	0
	179–140	1
	139–100	2
	<100	3
	Nutritional status	Total score
Degree by CONUT	Normal	0–1
	Light	2–4
	Moderate	5–8
	Severe	9–12

(Source: based on Ignacio de Ulíbarri J, et al, 2005.⁴⁰³)

1.3.2 GNRI

This index is a predictive index of complications and death in the older people over 65 years old. Like CONUT, it is suitable for screening, but is sensitive to albumin and body weight. Calculate using the formula at screening (Table 58).⁴⁰⁴ It has been reported that the incidence of cardiovascular events in chronic heart failure increases as the CONUT and GNRI values worsen.

Table 58. Nutritional Assessment by GNRI

GNRI value (14.89 × albumin level)	Nutritional status
≥98	Good
≥92 to <98	Low risk
≥82 to <92	Moderate risk
<82	High risk

(Source: based on Bouillanne O, et al, 2005.⁴⁰⁴)

1.3.3 GLIM Criteria

These criteria for diagnosing undernutrition were published in 2018.⁴⁰⁹ The diagnosis is made in 2 stages: assessment and diagnosis. In the first stage, nutritional screening, such as SGA, is performed, and if there is a problem with the nutritional status, the patient proceeds to the second stage. The diagnosis and severity of the disease are determined using assessment tools for current symptoms (rate of weight loss, low BMI, SMI) and etiology (decreased food intake or malabsorption, disease burden, or degree of inflammation). If ≥1 of the 3 current symptoms (weight loss, low BMI, low muscle mass such as SMI), or ≥1 of the 2 etiological factors are met, the patient is considered to be undernourished. In addition, the severity of the undernutrition will be evaluated based on current symptoms and classified as “moderate undernutrition” or “severe undernutrition”.

The type of undernutrition that should receive intervention depends on the “etiology” associated with the undernutrition and inflammation: (1) undernutrition with chronic disease and inflammation, (2) undernutrition with severe inflammation due to acute disease or trauma, (3) undernutrition due to chronic disease with little/no inflammation, and (4) undernutrition due to starvation without inflammation. Action should be taken on the issues that need to be improved (Figure 11).⁴⁰⁸

Figure 11.

Nutritional assessment by Geriatric Nutritional Index (GNRI) criteria. BIA, bioelectrical impedance analysis; BMI, body mass index; CT, computed tomography; DXA, dual-energy X-ray absorptiometry; MNA-SF, Mini Nutritional Assessment Short Form; MRI, magnetic resonance imaging; SGA, Subjective Global Assessment. (Source: based on Cederholm T, et al, 2019.⁴⁰⁸)

1.4 Use of Nutritional Assessment

If cardiac rehabilitation (CR) is conducted for undernourished patients with insufficient energy, it will lead to further muscle wasting and deterioration of nutritional status. Nutritional intervention may be necessary to supplement energy deficits, then observe changes in nutritional indicators, such as BW and muscle mass, and develop the next nutritional plan.⁴¹⁰ If the level of nutritional impairment is mild, it can be improved by adjusting the usual diet and between-meal eating, but in more severe cases, the need for supplemental nutrition and hospitalization increases. In heart failure patients with fluid volume changes, nutritional assessment is important for the early detection of unintentional muscle mass loss.⁴¹¹

2. General Diet Therapy for CVDs

2.1 Objective

Nutritional management in CR has 2 aspects: (1) nutritional management for lifestyle-related diseases that are the result of overnutrition, and (2) nutritional enhancement for undernutrition caused by the progression of heart failure (HF).^102,412 Nutritional management in CR is comprehensively determined within the CR team with reference to the severity of HF and the assessment of activities of daily living (ADL) and nutrition. The general diet for cardiovascular diseases (CVDs), including lifestyle-related diseases, is shown in Table 59.^413–416

Table 59. Nutritional Management Targeting Weight Control in Patients With CVD

1) Target BMI by age
18–49 years	18.5–24.9 kg/m2
50–64 years	20.0–24.9 kg/m2
≥65 years	21.5–24.9 kg/m2
2) Energy setting [kcal/day = IBW or ABW × physical activity*]
BMI 18.5 to 24.9 kg/m2	Use IBW
	Height m2× age-specific target BMI
BMI ≥27.5 kg/m2	Use ABW
	[(current weight in kg – IBW) × 0.25] + IBW
3) Protein target**	1.0–1.5 g/IBW/day 15–20% of energy
	Avoid eggs and fatty meats, and choose soy/processed soy products, and fish
4) Fat target	20–30% of energy
(1) Saturated fatty acid	4.5–7% Avoid fatty meats, animal fats, and milk fat
(2) Omega-3 polyunsaturated fatty acids	Choose blue fish
(3) Trans fatty acids	Avoid confectioneries that use shortening and margarine
(4) Cholesterol	<200 mg/day of cholesterol Avoid eggs and liver
5) Carbohydrate target	50–60% of energy Increase fiber and avoid sugar
	Choose brown rice, pressed barley, buckwheat, whole grain bread, and millet as staple foods
	Choose 1–2 mixed vegetables (mushrooms, seaweed, and legumes) with each meal
6) Alcohol consumption	≤25 g/day
7) Salt	<6 g/day

*Light exertion = 25–30 kcal, moderate exertion = 30–35 kcal, heavy exertion = 35 kcal. **Patients with complications of CKD are set individually. ABW, adjusted body weight; BMI, body mass index; CKD, chronic kidney disease; CVD, cardiovascular disease; IBW, ideal body weight. (Source: based on Atherosclerosis Society of Japan, 2017,⁴¹³ Ministry of Health, Labour and Welfare, 2019,⁴¹⁴ Japan Obesity Society, 2016,⁴¹⁵ Krenitsky J, 2005.⁴¹⁶)

Cardiac function decline affects nutritional status, and nutritional impairment increases the risk of developing heart failure and accelerates the severity of the disease.^102,412 Nutritional management in CR is aimed at preventing rehospitalization and performed to correct the coronary risk factors.^{102,130,413,417,418} Assessing changes in eating behaviors and making positive and affirmative associations with body size changes and laboratory results can help patients perceive success and enhance self-efficacy.⁴¹⁹

3. Intervention and Education for Patients With Heart Failure (Table 60)

Table 60. Recommendations and Levels of Evidence for Nutritional Interventions and Nutritional Counseling of CR in HF Patients

	COR	LOE	GOR (MINDS)	LOE (MINDS)
For HF patients, it is recommended to assess for possible undernutrition and the risk of undernutrition	I	C	B	IVa
Adequate energy intake and administration (resting energy expenditure of 22–24 kcal/kg/day × activity factor) should be considered. In older patients, with the aim of 20–30 kcal/kg/day as a guide, the dose should be increased or decreased according to the general condition of the patient, taking care not to inadequately consume energy or administer energy	IIa	C	C1	IVb
For insufficient intake due to decreased appetite, concomitant use of enteral nutrition (oral intake) should be considered	IIa	B	C1	II
Adequate protein intake and administration (≥1.1 g/kg/day) should be considered with attention to renal dysfunction. In older patients, the target should be ≥1.2 g/kg/day	IIa	B	C1	II
Counseling on weight measurement and recording, and periodic target weight reviews should be considered	IIa	C	C1	IVa
Reviewing the uniform salt restriction (<6 g/day), counseling may be considered for older patients with HF	IIb	C	C1	IVb
Aggressive nutritional therapy to improve the prognosis of older patients with endstage HF is not recommended	III (No benefit)	C	C2	VI

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

3.1 Nutritional Status and Prognosis

In patients with undernutrition, which is often observed in HF, exercise training alone is not expected to be effective and must be combined with nutritional counseling.^59,420,421 In the CHART-2 study, which is the observational study in Japan, the proportion of patients with mild or moderate undernutrition among patients with HF classification B, was 33.3% in those younger than 70 years and 43% in those older than 70 years.⁴²² In particular, older patients with HF have a higher probability of undernutrition because of nutritional deficits caused by the pathogenesis of HF, such as malabsorption of nutrients due to intestinal edema, decreased appetite, and imbalance of protein catabolism and anabolism, in addition to physiological changes due to aging.

The nutritional status of HF patients affects not only their physical function and body composition, but also their prognosis.^422–427 Moreover, undernutrition in patients over 70 years of age increases the risk of HF hospitalization,^422,425 and undernutrition in older patients with HF under outpatient treatment is associated with skeletal muscle loss,⁴²³ as well as decreased quality of life.⁴²⁸

Therefore, in the implementation of CR for HF patients, it is recommended that nutritional status is assessed individually, taking into account the high risk of undernutrition, and that counseling be given regarding appropriate energy intake according to age, basal metabolic rate, and activity level, as well as the intake of nutrients such as protein and salt.^412,429

3.2 Energy Requirements

Obesity is a risk factor for the development of HF, and energy restriction to prevent or reduce obesity is important for secondary prevention (see above Section 2. General Diet Therapy for CVDs). On the other hand, inadequate energy intake relative to energy requirements can lead to undernutrition. In an observational study of adult patients with stage B and C HF, the resting energy expenditure was 22–24 kcal/kg/day.⁴²¹ In an observational study of patients with advanced HF on a left ventricular assist device, the resting energy expenditure was 18kcal/kg/day.⁴³⁰ The resting energy expenditure plus the activity level is the energy requirement⁴³¹ (Table 61).⁴³²

Table 61. Calculation of Energy and Protein Intake Requirements for HF Patients

Measurement of resting energy metabolism by indirect calorimetry	Heart failure stage	Total energy requirement
If available	NYHA Classification I–IV AHA Stage B–D	Resting energy metabolism × activity factor*
If not available	NYHA Classification I–IV AHA Stage B–D	22–24 kcal/kg/day × activity factor
	Advanced heart failure	18 kcal/kg/day × activity factor

*Sitting most of the time = 1.0–1.4, low activity = 1.4–1.6, active = 1.6–1.9, very active = 1.9–2.5. Protein intake is calculated at 1.1–1.4 g/kg. (In patients with CKD, each patient should be considered individually.) If the actual body weight is ≥125% of the standard body weight (22 × height (m)²), the formula is: Corrected weight (kg) = (actual weight – standard weight) × 0.25 + standard body weight. HF, heart failure. (Adapted from Kuehneman T, et al, 2018⁴³² with modifications.)

Although there is a lack of evidence on the energy requirements of older patients with HF, the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline for energy requirements for all older patients, including those with HF, is 30 kcal/kg/day,⁴³³ and the Japanese Society for Clinical Nutrition and Metabolism (formerly, the Japanese Society for Parenteral and Enteral Nutrition) guideline suggests 20–30 kcal/kg/day.⁴³⁴ Even for the older patients with HF, the target energy dose should be 20–30 kcal/kg/day as well, but weight loss and thinness are associated with a poor prognosis in older patients with HF; thus it is recommended that the dosage be increased or decreased according to the patient’s general condition, always taking care to administer sufficient energy.

3.3 Decreased Appetite

Older patients are more prone to decreased energy intake due to decreased appetite compared with younger patients.⁴³⁵ In addition to decreased taste and digestive function,⁴³⁶ the severity of HF,⁴³⁷ inflammation, use of loop diuretics, and cachexia also contribute to decreased appetite.⁴³⁸ In patients with HF, decreased appetite has been shown to be associated with a poor prognosis, and also with decreased physical function.⁴³⁸

Oral nutritional supplements (ONS) for appetite loss in older people increase energy intake,⁴³³ but they do not improve skeletal muscle mass, exercise function, or indices related to HF.⁴³⁹ More evidence is needed on the effectiveness of ONS for decreased appetite in older patients with HF. In addition, salt restriction for the prevention of worsening HF may contribute to decreased appetite, and if the adverse effects of low nutrition are judged to be significant, relaxation of salt restriction and provision of meals tailored to preferences should be considered.⁴¹²

3.4 Protein Intake

In addition to the imbalance in protein catabolism and anabolism caused by HF,^421,440 the decline in muscle protein synthesis with age places older heart HF at high risk for developing sarcopenia and frailty. In addition to exercise, protein intake is necessary for skeletal muscle maintenance and muscle protein synthesis. In order to induce muscle protein synthesis, a certain level of amino acid concentration in the blood is required, but this threshold increases with age.⁴⁴¹ Therefore, it is necessary to consume sufficient protein at each meal, and even when the total daily protein intake is the same, the rate of muscle protein synthesis increases significantly when protein is consumed equally at all three meals. Therefore, dietary patterns should also be considered.⁴⁴²

The ESPEN guidelines recommend a protein intake of 1.2–1.5 g/kg/day for older adults with any acute or chronic disease, including HF.^433,443,444 The goal of protein intake for older patients with HF should be at least 1.2 g/kg/day, and in the case of chronic kidney disease, the need for protein restriction should be considered on a case-by-case basis.

3.5 Weight Management

Patients with HF should measure and record BW every day, and it is important to support self-monitoring for early detection by self-examination of early symptoms and physical findings of acute exacerbation of HF. The target weight should be determined comprehensively based on the physical findings and examination results of each patient. The target weight should be reviewed periodically because weight varies not only with fluid volume but also with nutritional status. Although there is no single index for determining weight fluctuations due to fluid volume or nutritional status, it should be noted that the amount of stored energy required to gain 1 kg of BW is approximately 7,000 kcal, and weight fluctuations due to nutritional status take a relatively long time.

Studies documenting the optimal BMI for HF patients are lacking, and the relationship between intentional weight gain and prognosis in HF patients is unclear. European guidelines and the Heart Failure Society of America do not recommend weight loss for HF patients with a BMI of <35 kg/m², but more evidence is needed in Japan to account for differences in body size.⁴⁴⁵

3.6 Salt Intake

The Japanese guidelines suggest a salt intake of <6 g/day for HF patients,¹⁰² but there is a lack of evidence that salt restriction improves life expectancy and QOL in patients with symptomatic HF. Three recently published randomized controlled trials in patients with HF with reduced ejection fraction and an observational study including patients with HF with preserved ejection fraction all showed a poor prognosis in the salt-restricted group.^446–448 In addition, salt restriction may decrease appetite and worsen nutritional status in older patients. Therefore, it is advisable to examine whether the effect of salt restriction outweighs the risk of undernutrition in each individual case, and to revise strict salt restriction as appropriate depending on dietary intake.^102,412

VII. QOL and Psychological Assessment and Intervention

1. Methods and Indicators for Assessing Quality of Life (Table 62)

Table 62. Recommendations and Levels of Evidence for Improvement of QOL With CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In patients with CAD, CR is recommended to improve QOL	I	A	A	I
In patients with HF, CR is recommended to improve QOL	I	A	A	I
Use of the SF-36 should be considered to assess QOL in patients with CAD	IIa	A	B	I
The Minnesota Living with Heart Failure Questionnaire (MLHFQ) should be considered to use as a measure of QOL in patients with HF	IIa	A	B	I

CAD, coronary artery disease; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence; QOL, quality of life.

1.1 QOL With a Focus on Health

In the field of health and medical care, such as medical treatment, rehabilitation mental health care, nursing, and care, the quality of life (QOL) scale has been used to a large extent as a standard to evaluate the effectiveness of interventions. In this case, health-related QOL (HRQOL) is used in the health and medical fields to focus on factors directly related to health, excluding QOL related to social environmental factors such as economic status, living environment, and sanitary conditions.⁴⁴⁹ HRQOL was used in a study of the effects of treatment in inoperable cancer patients, which led to its current wide use for chronic disease.

1.2 Evaluation Scale (Evaluation Method)

There are many different measurements of QOL, and Table 63 lists the primary measurements developed to date.

Table 63. Primary Measurements of Quality of Life

Name	Features	Time required
SF-36 v2® (Japanese version) (Japanese version of MOS 36-Item Short-Form Health Survey)	36 items with the following subscales: (a) physical function, (b) daily role function (physical), (c) body pain, (d) overall health, (e) vitality, (f) social function, (g) daily role function (mental), (h) 8 subscales and 3 components of mental health: QOL Physical Component Summary (PCS), Mental Component Summary (MCS), and Role/social Component Summary (RCS)	10 min
SF-12® (Japanese version) (Japanese version of MOS 12-Item Short-Form Health Survey)	12 items; subscales are the same as the SF-36 v2	2–3 min
SF-8TM (Japanese version) (Japanese version of MOS 8-Item Short-Form Health Survey)	8 items, subscales are the same as the Japanese version of SF-36 v2	1–2 min
WHOQOL-26 (World Health Organization Quality of Life-26)	26 items with 5 levels of response, including “not at all”, “a little”, “somewhat”, “much”, and “very much” 4 domains (physical, psychological, social relationships, and environmental) and a subscale for overall QOL	10 min
EQ-5D-5L (Japanese version) (Japanese version of EuroQOL 5 dimensions 5-level)	15 items and includes subscales for mobility, personal care, daily activities, pain/ discomfort, and anxiety/depression	5 min
Heart QOL	14 items, with subscales for physical, emotional, and overall QOL, which were developed by the European Association of Preventive Cardiology (EAPC)	5 min
MLHFQ (Japanese version) (Japanese version of Minnesota Living with Heart Failure Questionnaire)	21 items and includes subscales for shortness of breath, sleep, fatigue, and appetite	5 min

1.3 Evaluation of Improvement Effects

Many reports document that cardiac rehabilitation (CR) is effective in improving QOL.⁴⁵⁰ There are reports that QOL can be improved by general exercise training programs,⁴⁵¹ but there are also comprehensive programs that include psychological counseling, stress management, and patient education. A comparison of the 2 programs showed that the comprehensive program had a greater effect on improvement.

1.3.1 CAD

In a study comparing exercise training alone and exercise training plus counseling in patients with coronary artery disease (CAD), QOL improved only in the exercise training plus counseling group.⁴⁵² Furthermore, a meta-analysis of randomized controlled trials (RCTs) examined the effect of psychological intervention on QOL in addition to exercise training, and the result showed that not only were anxiety and depression scores significantly lower in the intervention group (2,024 patients) than in the control group (1,156 patients), but also mortality and morbidity were lower, pointing to the importance of psychological intervention in conjunction with exercise training; the improvement in QOL was higher in women than in men.⁴⁵³

1.3.2 Chronic Heart Failure

Psychological support and intervention programs have been reported to be effective in reducing anxiety and depression, improving QOL, and reducing the number of rehospitalizations in patients with HF.⁴⁵⁴ The causes of hospitalization for exacerbations in older patients with chronic HF are more likely to be due to poor medication compliance, inability to restrict fluids and salt, and social isolation, such as living alone, than to the deterioration of the condition itself; therefore, a comprehensive response is needed in addition to direct therapeutic management of the disease.⁴⁵⁵ In a recent meta-analysis of four RCTs (299 patients), significant improvement in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was reported in patients with chronic HF after a brief exercise intervention.⁴⁵⁶ In addition, 13 studies (3,990 patients) using the HRQOL showed a significant improvement in exercise capacity in the CR group based on exercise training, compared with the control group.⁴⁵⁷ There is sufficient evidence for the effectiveness of QOL assessment in patients with chronic HF, and QOL assessment using the MLHFQ is recommended in Japan.

2. Psychological Evaluation (Table 64)

Table 64. Recommendations and Levels of Evidence for Psychological Assessment (Methods and Indicators of Anxiety and Depression) in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
In patients with CAD, screening for depression is recommended	I	A	A	I
It is recommended to use the PHQ-9 and other scales to assess depressive symptoms in patients with CAD	I	A	A	I
In patients with CAD, evaluation of cognitive function may be considered, keeping in mind the possibility of depression or delirium	IIb	A	A	I
DS-14 may be considered for assessment of personality traits in patients with CVD	IIb	B	B	II

CAD, coronary artery disease; COR, class of recommendation; CR, cardiac rehabilitation; CVD, cardiovascular disease; GOR, grade of recommendation; LOE, level of evidence.

2.1 CVD and Depressive/Anxiety Symptoms

Depressive symptoms are symptoms that accompany various diseases, but their prevalence is higher in patients with cardiac diseases, ranging from 17% to 27% which is nearly 3-fold higher than in the general population (10.3%).⁴⁵⁸ In HF, in particular, the prevalence of depression increases with the severity of the disease, and it is said to be as high as 42% in NYHA Classification IV.⁴⁵⁹ Depressive symptoms and various other mental and psychological symptoms have a negative effect on the condition, prognosis, and QOL in cardiovascular diseases (CVDs). The AHA has recommended screening for depression and intervention for depression in patients with CVDs.⁴⁶⁰ Anxiety has also received attention as a factor affecting CAD as well as depressive symptoms.⁴⁶¹

2.2 Mental and Psychological Features

As for the behavioral characteristics of CVD patients, starting with Type A behavioral patterns defined in 1959, the effects of anger and hostility have been studied, and now Type D (personality tendency), negative and repressive coping behaviors, is attracting attention as a factor in the onset of CVDs.⁴⁶² This type of personality is characterized by a tendency to perceive things negatively, but also by perseverance and difficulty in expressing one’s own intentions, and it has been reported that cardiac patients with Type D have poor perceived health.⁴⁶³

In a meta-analysis based on major adverse cardiovascular events for CAD, anger/hostility, depression, and distress were reported as psychological factors associated with major disease events in women, and anxiety, depression, and distress were reported in men.⁴⁶⁴

2.3 Questionnaire-Based Screening

In CR, questionnaire-based screening tests for psychiatric symptoms and cognitive functions are also used to assess the mental and psychological status of patients. These tests are simple and useful auxiliary diagnostic tools that can quantify the presence and severity of symptoms even in the absence of a professional, but unfortunately, the fact that the examinee can easily manipulate the results renders these tests to be possibly biased.

Table 65 summarizes psychological tests and assessment scales for mental and psychological aspects that are frequently used in the field of CR. The diagnosis of depression should not be made on the basis of screening results, but should be based on diagnostic criteria such as DSM-V (American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edition).⁴⁶⁵ In order to diagnose dementia, it is necessary to exclude secondary deterioration of brain function by blood tests and CT/MRI of the brain, and it is difficult to diagnose dementia or mild cognitive impairment based only on the results of screening tests.

Table 65. Psychological Tests Commonly Used in CR

PHQ-9
Formal name	Patient Health Questionnaire for Depression Screening-9
Features	9-question screening test for depression based on the diagnostic criteria for depression, widely used in medical institutions internationally
	A score of 0–4 indicates no symptoms, 5–9 indicates mild depression, 10–14 indicates moderate depression, 15–19 indicates moderate to severe depression, and 20–27 indicates severe depression
Time required	5–7 min
PHQ-2
Formal name	Patient Health Questionnaire for Depression Screening-2
Features	Screening is possible with 2 questions (the first 2 questions of PHQ-9) for depression
	Symptoms are rated as follows: “Never” =0 points, “A few days” =1 point, “More than half” =2 points, and “Almost every day” =3 points. If the score is ≥1 for any of the 2 questions, reevaluation by PHQ-9 is recommended. A score of ≥3 out of 6 is sometimes considered “symptomatic”
Time required	1–2 min
CES-D
Formal name	Center for Epidemiologic Studies Depression Scale
Features	Screening test for depression developed by the U.S. National Institute of Mental Health (NIMH) based on existing scales such as SDS and MMPI
	The number of questions is as small as 20, and simple. A score of ≥16 indicates depressive symptoms
Time required	10–15 min
HAM-D/HRSD
Formal name	Hamilton Depression Rating Scale/Hamilton Rating Scale for Depression
Features	Rating scale for severity of depression
	It is not a self-rating system, but an interview conducted by a trained physician or other professional. 0–7 points: normal, 8–13 points: mild, 14–18 points: moderate, 19–22 points: severe, ≥23 points: most severe
Time required	10–20 min
BDI/BDI-II
Formal name	Beck Depression Inventory
Features	Depressive symptoms and their severity are assessed by a total score of 63 points, calculated from 0 to 3 points for each of the 21 items. 0–13 points: very mild, 14–19 points: mild, 20–28 points: moderate, and 29–63 points: severe
	*Version II was revised after DSM-IV
Time required	5–10 min
SDS
Formal name	Self-rating Depression Scale
Features	Rating scale for depression
	20-item questionnaire with 4-point self-assessment. Consists of questions about emotional, physiological, and psychological symptoms. Half of the items are reversal items. A total score of <40 points: slight depression, 40-point range: mild depression, ≥50 points: moderate depression
Time required	10–15 min
HADS
Formal name	Hospital Anxiety and Depression Scale
Features	Test for depressive and anxiety symptoms in patients with physical illness
	The test consists of 7 questions for anxiety and depression, respectively. The total score is calculated from 0 to 3 points for each question: 0–7 points: no symptoms, 8–10 points: suspicious, ≥11 points: symptoms
Time required	5–10 min
GAD-7
Formal name	Generalized Anxiety Disorder-7
Features	Screening test for generalized anxiety disorder (GAD)
	Consists of 7 items, each with a score of “never”: 0 point, “a few days” (out of 2 weeks): 1 point, “more than half of the time”: 2 points, and “almost every day”: 3 points. The total symptom score is 0–4 points: normal, 5–9 points: mild, 10–14 points: severe
Time required	5–7 min
DS-14
Formal name	Type D Scale-14
Features	Measure of Type D (distress) personality, which is common in patients with heart disease
	Consists of 2 items, Negative Affect (NA) and Social Inhibition (SI). Each of the 7 items has a score of 0–4: score of ≥10 on both NA and SI indicates Type D
Duration	5–7 min
MMSE
Formal name	Mini-Mental State Examination
Features	Screening test for dementia consists of 11 items: time and place awareness, immediate and delayed reproduction of 3 words, calculation, object calling, sentence recitation, 3-step verbal commands, writing commands, writing sentences, and graphic copying. On a 30-point scale, ≤23 points: suspected dementia, ≤27 points: suspected mild cognitive impairment
Duration	6–10 min
Mini-Cog
Formal name	Mini-Cognitive Assessment Instrument
Features	Simple screening test for dementia consists of 3 tests: immediate and delayed reproduction and clock drawing of 3 words; score of ≤2 indicates suspicion of dementia
Duration	2 min
MoCA-J
Formal name	Japanese version of Montreal Cognitive Assessment
Features	Screening test for mild cognitive impairment includes visuospatial and executive functions, naming, memory, attention, recitation, word recall, abstract concepts, delayed replay, and disorientation. Score of ≤25 points indicates suspected mild cognitive impairment
Duration	10 min
TMT
Formal name	Trail Making Test
Features	Frontal lobe dysfunction: a measure of executive function (e.g., attention/processing speed). It assesses many functions such as attention, number and letter recognition qualification search, eye/hand coordination, speed of information processing, flexibility of mental activity, and exercise capacity
Duration	15 min

CR, cardiac rehabilitation.

3. Psychological Intervention and Counseling (Table 66)

Table 66. Recommendations and Levels of Evidence for Psychological Interventions and Counseling in CR for Patients With CAD

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform CR to improve depressive symptoms	I	A	A	I
It should be considered to administer antidepressants and to conduct psychotherapy, such as cognitive behavioral therapy, to improve depressive symptoms	IIa	B	B	II

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

3.1 Communicating With the Patient

It has been reported that many patients with CVD are in an ambivalent state of mind, having a variety of concerns such as “How can I get back to normal?” But at the same time, they are ambivalent about discussing these concerns with their health care providers.⁴⁶⁶ Therefore, it is expected that they are unlikely to voluntarily consult a healthcare professional and take action for improvement. It is desirable to understand and support such a psychological state by utilizing screening tests.

3.2 Dealing With Depression and Other Psychological Symptoms

In general, psychotherapy, including psychoeducation and cognitive-behavioral therapy, and pharmacotherapy as needed are useful as basic interventions for depression and anxiety symptoms. It has been reported that exercise, which is practiced in CR, has a moderate effect on depressive symptoms, in addition to reducing the risk of CVD, stroke, and diabetes.⁴⁶⁷

Regarding psychological interventions for patients with CAD, a meta-analysis of 35 studies (total of 10,703 patients) reported that traditional psychotherapeutic interventions did not affect the overall mortality and recurrence rates of CAD, but did reduce cardiac mortality and depressive, anxiety, and stress symptoms.⁴⁶⁸

3.3 Integrated Support (Collaborative Care)

It has been reported that the combination of exercise and pharmacotherapy can improve depression, but a recent meta-analysis reported that exercise-based CR was effective in improving depression and anxiety in myocardial infarction patients.⁴⁶⁸ CR can provide a variety of mental and psychological supports from multiple professions, rather than single support from psychological professionals. Collaborative care (integrated support) can improve depression, anxiety, and QOL in CVD patients even when psychiatrists and other medical specialists are not available to treat the psychiatric and psychological symptoms, and studies on the effects of this support method have been conducted in recent years.⁴⁶⁹ Taking advantage of the characteristics of CR as team medical care, it is necessary to create an environment in which multiple professionals can utilize the essence of psychotherapy and other methods in their respective patient education and support.

VIII. Patient Education and Disease Management

1. Methods of Patient Education, Evaluation Methods and Evidence (Table 67)

Table 67. Recommendations and Levels of Evidence for Patient Education in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to educate patients with CAD in order to improve HRQOL and prevent cardiovascular death and rehospitalization	I	B	B	II
It is recommended to educate patients with chronic heart failure in order to improve their HRQOL and prevent rehospitalization	I	B	B	II

CAD, coronary artery disease; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HRQOL, health-related quality of life; LOE, level of evidence.

1.1 Methods

In randomized controlled trials that have evaluated the effectiveness of patient education in cardiac rehabilitation (CR), a variety of educational methods were reported.^{221,470–473} A 1-year outpatient psycho-educational consultations follow-up that included 12 weeks of physical activity and 4 psycho-educational consultations,²²¹ a 3-week self-management program that included bidirectional interactive sessions (60–75 min) with patients by a multidisciplinary team,⁴⁷⁰ and a 36-month regular telephone intervention follow-up aimed at secondary prevention⁴⁷³ have been reported. However, it is difficult to manage the necessary time to provide patient education in addition to exercise training in conventional CR, which lasts ≈1 h/session, and there are limitations to multidisciplinary intervention. In the USA, “Intensive CR” began reimbursement in January 2011 for patients with angina pectoris, after coronary artery bypass grafting, heart failure, left ventricular assist device, and after heart transplantation. During each 4-h session, patients receive 1 h of supervised exercise. In addition, they receive 1 h of stress management, a 1-h group support session, and a 1-h group meal with a lecture.⁴⁷⁴ Although the standard CR program is an exercise-based program that consists of 1 h of exercise 3 times/week for 12 weeks (total of 36 h), the Intensive CR program consists of 2 sessions/week for 9 weeks (total of 72 h), and becomes a more systematic and intensive educational CR program (Table 68).⁴⁷⁴

Table 68. Intensive Educational and Conventional CR Programs in the USA

	Intensive and Educational CR	Normal CR
Program structure (Time required)	Physician-supervised exercise (1 h) Nutritional education (1 h)* Stress management (1 h) Group support (1 h)	Mainly supervised exercise training, with some patient education (1 h)
Insurance coverage in the USA	4 h per session, twice each week, for 9 weeks (72 h in total)	1 h per session, 3 times/week, for 12 weeks (36 h in total)

*Balanced diet with a focus on vegetarian food (limited intake of processed foods, refined carbohydrates, trans-fatty acids, saturated fatty acids, and animal proteins). CR, cardiac rehabilitation. (Source: based on Freeman AM, et al, 2019.⁴⁷⁴)

Patient education in CR covers a wide range of topics, including exercise, nutrition, stress management, and returning to work/social life. In patient education, it is important to increase the patient’s adherence to CR. To achieve this, the following approaches have been proposed: strengthening motivation, continuous and professional education by healthcare providers, and social support from key persons.^475,476 Improvement of the patient’s adherence to exercise training and lifestyle changes can be achieved if perceived benefits in quality of life (QOL) are better after intensive intervention.

It has also been reported that education in CR can improve the lifestyle of patients.^9,477,478 In recent years, the importance of enhancing individual health literacy has been reported.⁴⁷⁹ Health literacy refers to the knowledge, motivation, and ability to obtain, understand, evaluate, and utilize health information. As for the evaluation indicators for health literacy, objective evaluation of skills, group-level evaluation, and self-reported evaluation have been reported.⁴⁸⁰ In CR, it is necessary to check the health literacy of patients and provide them with individualized educational content.

1.2 Evaluation of Effectiveness

The effectiveness of patient education in CR has been reported in terms of the following: (1) physical function, (2) coronary risk factors, (3) participation rate in CR programs, (4) exercise rate, (5) self-management ability, (6) satisfaction, (7) self-efficacy, (8) knowledge, and (9) QOL.^{221,470–473,481,482} Assessment methods include exercise testing, blood tests, and psychosocial measures (depression, anxiety, social support, and adherence).

2. Management of Coronary Risk Factors, Smoking Cessation Counseling (Table 69)

Table 69. Recommendations and Levels of Evidence for Coronary Risk Factor Management and Smoking Cessation Counseling in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform comprehensive CR for smoking cessation, weight control, blood pressure (including home blood pressure measurement), lipids, and blood glucose	I	A	A	I

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

2.1 Evidence

Correcting coronary risk factors is one of the goals of CR. Table 70 shows the definition of each coronary risk factor and the target values for control.^483–485

Table 70. Diagnosis of Coronary Risk Factors and Management Targets in CR

Coronary risk factors	Diagnostic criteria	Management targets
High blood pressure	(1) Office blood pressure ≥140/90 mmHg (2) Out-of-office blood pressure 　 Home blood pressure ≥135/85 mmHg 　 24-h blood pressure ≥130/80 mmHg 　 Nocturnal blood pressure ≥120/70 mmHg (1) or (2)	Office blood pressure CAD: <130/80 mmHg Systolic blood pressure in heart failure: <130 mmHg in patients with preserved left ventricular contractility, 110–130 mmHg in patients with reduced left ventricular contractility
Dyslipidemia	LDL-C ≥140 mg/dL HDL-C <40 mg/dL TG ≥150 mg/dL Non-HDL-C ≥170 mg/dL Any of the above	CAD: LDL-C <100 mg/dL, non-HDL-C <130 mg/dL HDL-C ≥40 mg/dL, TG <150 mg/dL In patients with prior ACS, familial hypercholesterolemia, diabetes mellitus, and/or atherothrombotic stroke, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL
Diabetes mellitus/ impaired glucose tolerance	(1) Fasting blood glucose ≥126 mg/dL (2) Casual blood glucose ≥200 mg/dL (1) or (2) and HbA1c ≥6.5% Impaired glucose tolerance: fasting glucose ≥110 mg/dL or ≥140 mg/dL at 2 h after loading	HbA1c <7.0% In individuals older than 65 years old, less than 8.0–8.5%, taking into account for cognitive function, ADL decline, and hypoglycemic risk
Obesity/metabolic syndrome	Waist circumference: men ≥85 cm, women ≥90 cm In addition to the above, at least 2 of the following items (1) Fasting TG ≥150 mg/dL or HDL-C ≤40 mg/dL (2) Systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg (3) Fasting glucose ≥110 mg/dL	Correction of the left column BMI <25 kg/m2
CKD	(1) Urinalysis, imaging, hematology, and pathology show the presence of renal damage, especially proteinuria ≥0.15 g/gCr (albuminuria ≥30 mg/gCr) (2) eGFR <60 mL/min/1.73 m2 Either or both (1) and (2) persists for more than 3 months	eGFR ≥60 mL/min/1.73 m2
Physical inactivity	All awake actions with energy expenditure ≤1.5 METs
Smoking	Cigarettes, cigars, electrically heated cigarettes, electronic cigarettes	No smoking and avoidance of passive smoking

eGFR = 194 × Cr^−1.094 × age^−0.287 × 1 (× 0.739 for women). Fasting is defined as blood collection during fasting for ≥10 h. ACS, acute coronary syndrome; BMI, body mass index; CAD, coronary artery disease; CKD, chronic kidney disease; CR, cardiac rehabilitation; eGFR, estimated glomerular filtration rate; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; MET, metabolic equivalent; non-HDL-C, total cholesterol-HDL-C, TG, triglyceride.

A meta-analysis of 48 randomized controlled trials (RCTs) reported through 2003 examined the effects of CR in patients with coronary artery disease (CAD) and found significant improvements in total mortality (−20%), cardiovascular disease mortality (−26%), total cholesterol (−14.3 mg/dL), triglyceride (TG) (−20.4 mg/dL), systolic blood pressure (−3.2 mmHg), and smoking rate (−36%) in the CR group compared with the no-CR group.⁴⁸⁶ In a meta-analysis of 19 RCTs of exercise-based CR, approximately half of the reduction in cardiac death (−28%) was attributed to correction of coronary risk factors such as smoking cessation, lowering of cholesterol, and lowering of systolic blood pressure, with smoking cessation having a particularly large effect.⁴⁸⁷ In a study of 7,998 patients younger than 80 years who experienced acute coronary syndrome or underwent revascularization (CABG or PCI) in Europe, the rate of smoking cessation was significantly higher in the CR group, and the proportion of obese patients was lower.⁴⁸⁸

As already stated, a comprehensive CR program is useful for reducing smoking rates, controlling body weight, and improving blood pressure, lipid metabolism, and glucose tolerance.^486,489

2.2 Hypertension and Blood Pressure Control

Hypertension is the greatest risk factor for cardiovascular disease (CVD).⁴⁸³ It is strongly associated with the development of CAD and heart failure in particular. Adequate and sustained lowering of blood pressure reduces the incidence of CVD and death from CVD, regardless of age, sex or comorbidity.⁴⁸³ The antihypertensive effects of moderate- to vigorous-intensity aerobic exercise and handgrip exercise have been established in a number of meta-analyses.⁴⁸³

2.3 Dyslipidemia and Lipid Management

The efficacy of lowering low-density lipoprotein cholesterol (LDL-C) for primary and secondary prevention of CAD has been established according to meta-analyses of large-scale RCTs. The absolute reduction in cardiovascular events correlated with LDL-C lowering, and the absolute reduction in events was particularly greater in high-risk patients, indicating the significance of aggressive lowering of LDL-C.⁴⁹⁰ In cohort studies, large-scale RCTs, and meta-analyses, high levels of non-high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG), and a low level of HDL-C have been indicated as residual risks on statin therapy.^491–493

2.4 Diabetes and Blood Glucose Control

Diabetes mellitus (DM) promotes atherosclerosis and is a cause of myocardial infarction (MI), stroke, aortic aneurysm and peripheral atherosclerotic disease, as well as heart failure (HF) and atrial fibrillation.⁴⁹⁴ DM is also a prognostic factor for MI and HF.⁴⁹⁵ The risk of CVD increases from the time of glucose intolerance and postprandial hyperglycemia before the development of DM. Therefore, it is important to evaluate postprandial hyperglycemia, decreased insulin secretion, and insulin resistance by oral glucose tolerance tests.⁴⁹⁴

It is well established that exercise training and increased daily physical activity are effective in lowering blood glucose levels in type 2 DM.^485,496

2.5 Obesity, Metabolic Syndrome

Metabolic syndrome (MS) is a condition characterized by a combination of coronary risk factors based on insulin resistance associated with visceral fat accumulation. In a meta-analysis of 15 RCTs examining the effects of CR on MS and its components, CR significantly improved the incidence of MS by −22%, HDL-C by +2.13 mg/dL, waist circumference by −2.25 cm, systolic blood pressure by −6.2 mmHg, diastolic blood pressure by −2.53 mmHg, TG by −27.45 mg/dL, and fasting glucose by −6.42 mg/dL.⁴⁹⁷

2.6 CKD

Chronic kidney disease (CKD) is a risk factor not only for endstage renal failure but also for CVD.⁴⁸⁴ In patients with heart disease who participated in outpatient CR for 3–5 months, eGFR was significantly improved in patients with CKD.^498,499

2.7 Physical Inactivity

Prolonged sedentary time is a risk factor for the development of CVD and DM and for total mortality, independent of physical activity.^484,500

There is no consensus on whether CR decreases sedentary time. In a meta-analysis of 9 RCTs comparing patients using physical activity monitoring devices (wearing group) with those who did not (not wearing group) during maintenance CR, there was a significant improvement in exercise capacity and an increase in the number of steps taken in the wearing group.⁵⁰¹ Wearable physical activity monitoring devices are useful for increasing daily physical activity.

2.8 Smoking and Smoking Cessation Counseling

Smoking (including cigarettes and cigars) is an independent risk factor for all CVDs and significantly increases the risk of CVD death and total mortality. Exposure to even small amounts of tobacco smoke significantly increases the risk of CVD.⁵⁰² The risk of developing CAD due to smoking is 25% higher in women than in men.⁵⁰³

Passive smoking significantly increases the risk of developing CAD by 1.3-fold. Enactment of antismoking laws in communities and workplaces has significantly reduced the incidence of acute myocardial infarction (AMI) by 20% after 12 months, and the longer the period after enactment, the more pronounced the effect.⁵⁰⁴

Smoking cessation reduces the risk of disease progression, morbidity, and mortality in patients, irrespective of the presence of CVD, and this effect is seen in patients of any age and sex.⁴⁸⁴ A meta-analysis of cohort studies of patients with CAD showed that smoking cessation reduced the relative risk of death by 36%.⁵⁰⁵ Another multicenter observational study that enrolled patients with AMI in Japan showed that the multivariate-adjusted hazard ratio for mortality was 2.27-fold higher in continuing smokers than in nonsmokers.⁵⁰⁶

The 5A approach (Ask, Advice, Assess, Assist, Arrange) is recommended as a method of teaching smoking cessation.⁵⁰⁷ Newer forms of cigarettes (such as electrically heated cigarettes and e-cigarettes), which are different from traditional cigarettes, have been reported to be harmful to health due to the aerosols they produce⁵⁰⁸ and thus should be avoided. Although exercise training itself is not directly linked to smoking cessation, comprehensive CR can motivate patients to continue exercise and smoking cessation.

3. Self-Management and Lifestyle Interventions for Heart Failure (Table 71)

Table 71. Recommendations and Levels of Evidence for Self-Management and Lifestyle Interventions in CR of HF Patients

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to provide education and support to improve self-care	I	A	A	I
It is recommended to utilize social resources	I	A	A	I
It is recommended to provide smoking cessation education	I	C	B	IVb
It is recommended to provide exercise instruction	I	B	B	II
It should be considered to counsel about their alcohol intake	IIa	C	C1	VI
It should be considered to provide salt reduction instruction	IIa	C	C1	VI
It should be considered to provide education on appropriate calorie intake	IIa	C	C1	VI
It should be considered to provide education on infection prevention and vaccination	IIa	C	B	IVb
Sleep instruction may be considered	IIb	B	C1	II

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

Self-management of heart failure (HF self-care) is the process of making decisions about all behaviors in daily life that are necessary to maintain a stable state without worsening symptoms.⁵⁰⁹ Self-care is considered essential in the management of HF to avoid acute worsening and increasing the risk of death.⁵¹⁰ Patient education on how to recognize and appropriately manage HF symptoms is important.^102,445,511

Self-care involves adherence to treatment and healthy lifestyle activities (e.g., adherence to medication, exercise, proper diet) (Process 1: Self-Care Maintenance), as well as being aware of HF symptoms and being able to understand their meaning (e.g., being aware of shortness of breath and edema and being able to determine that fluid retention is occurring). Self-care monitoring, such as weight measurement, home blood pressure measurement, and self-monitoring of pulse, is useful for understanding HF symptoms (Process 2: Awareness and Understanding of Heart Failure Symptoms). Finally, the goal is to be able to take appropriate action when HF symptoms are recognized (e.g., see a doctor promptly when symptoms worsen) (Process 3: Self-Care Management). These three processes include elements that can be resolved by the patient’s own decisions and elements that require consultation with medical personnel, such as medication.⁵⁰⁹

Self-care behaviors vary depending on disease-specific factors (e.g., degree of HF symptoms, complication status), personal factors (e.g., cognitive function, culture, faith), and environmental factors (e.g., social isolation, availability of social resources, living environment, economic environment). In order to improve and sustain self-care, it is important to gain a sense of self-efficacy not only through knowledge but also through one’s own successes and the experiences of others.⁵¹²

4. Disease Management in Outpatient CR (Table 72)

Table 72. Recommendations and Levels of Evidence for Disease Management in Outpatient CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
For patients with chronic HF, it is recommended to provide disease management by a multidisciplinary team	I	B	A	II
For patients with CAD, it should be considered to provide disease management by a multidisciplinary team	IIa	B	B	III

CAD, coronary artery disease; COR, class of recommendation; GOR, grade of recommendation; HF, heart failure; LOE, level of evidence.

4.1 Significance and Challenges of Disease Management

A disease management program is a systematic program that aims to improve prognosis, including reduction in rehospitalizations, through standardized medical care and patient education based on medical guidelines. Outpatient CR is also a disease management program that focuses on exercise training, medication counseling, dietary counseling, lifestyle intervention, counseling, correction of coronary risk factors, and management of acute exacerbation.¹⁰ The outcomes of disease management in outpatient CR are improvement of life expectancy, prevention of rehospitalization, and prevention of physical deterioration. For this purpose, it is important to support patients and their families to continue appropriate self-management behaviors in their daily lives.

Outpatient CR is a comprehensive program developed by a multidisciplinary team (physicians, nurses, physical therapists, health and exercise instructors, pharmacists, dietitians, clinical psychologists/licensed psychologists, etc.) and is useful as a system for effective disease management. In addition, outpatient CR is an ideal setting for patients to receive necessary lifestyle intervention because it is monitored and patients can receive appropriate observation and counseling on their physical condition during and after exercise training from a multidisciplinary team.⁴⁷⁸

Davidson et al reported that for patients hospitalized with moderate HF, after 3 months of outpatient CR intervention (weekly supervised exercise training, HF assessment by a nurse specialist, and multidisciplinary educational counseling, home exercise training counseling, and telephone counseling), QOL, 6MWD, and HF severity improved, and readmission rates were significantly lower by 1 year.⁹ These results indicate that outpatient CR programs not only improve exercise capacity, but also improve QOL, prevent rehospitalization, and are useful as disease management programs. A systematic review of disease management in HF showed that multidisciplinary interventions reduced all-cause death and that case management by nurses with specialized training may reduce the rate of rehospitalization for HF or any cause.⁵¹⁴

A report from Europe showed that outpatient CR, including a disease management program after acute myocardial infarction, significantly improved all-cause death by 38% at 1 year in a backward-looking observational study using propensity score matching.⁵¹⁵ In another observational study, a significant improvement in exercise capacity and coronary risk factors was observed with active participation in outpatient CR, even in the low-risk group.¹¹³

Recently, a survey on multidisciplinary collaborative care and CR for HF patients reported that although the implementation rate of outpatient CR was 56.5%, only 7% of patients hospitalized for HF received outpatient CR after discharge.¹⁶⁶ For patients hospitalized for CAD or HF, comprehensive educational support is provided during hospitalization based on acute rehabilitation but after discharge, systematic disease management and lifestyle intervention are discontinued in the outpatient clinic, despite significant changes in the living environment, such as diet and physical activity.⁵¹⁶ Therefore, increasing the prevalence of outpatient CR, especially after hospital discharge, is a major challenge.

4.2 Disease Management in Practice

At the introduction of outpatient CR, the CR staff evaluates coronary risk factors, cardiac function, and exercise capacity, confirms the purpose of CR with the patient, collects and evaluate information on lifestyle and provides consultation, support, and counseling. At each outpatient visit for CR, self-monitoring of physical symptoms before and during exercise and educational support for daily life are provided (see Figure 5). After that, periodic evaluations (after 1 month, 3 months, 6 months, 1 year, and every year thereafter) should be performed, and disease management be based on the evaluation results. After outpatient CR is completed, it is expected that a system will be established that will lead to evaluation and disease management in the maintenance CR setting.

4.3 Inter-Professional Collaboration (Table 73)

Table 73. Recommendations and Levels of Evidence for Inter-Professional Collaboration in CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It is recommended to perform CR by a multidisciplinary team including doctors, nurses, physical therapists, occupational therapists, and others	I	C	A	III

COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

4.3.1 Occupations Comprising Team Medicine

Table 74 shows the components of CR and the occupations, roles, and responsibilities of the staff involved. CR is a comprehensive intervention that can improve ADL and QOL by restoring systemic functions. CR can also help patients recover from cardiac dysfunction and prevent recurrence by creating a good systemic environment for the heart. In other words, CR is the setting in which patients are evaluated, monitored, and trained to educate themselves in self-management to prevent recurrence. For this purpose, it is ideal to form a multidisciplinary team that includes the following professionals: (1) cardiologist, (2) CR nurse with specialized training, (3) physical or occupational therapist, (4) specialist who prescribes exercise and instructs exercise training, (5) clinical laboratory technician who is in charge of exercise stress tests, (6) dietitian, and (7) others such as a clinical or licensed psychologist, pharmacist, and social worker.

Table 74. Division of Roles of Staff Involved in CR

Role		Profession
Facility director	Management and operation of the facility Management responsibility	Cardiologist
Exercise training	Create exercise program Provide counseling to exercise instructors	Physical therapists, occupational therapists, nurses, health fitness programmer, etc. Exercise instructors
	Exercise program implementation	Physical therapist, occupational therapist, nurse, health and exercise instructor, etc. Exercise instructors
Diet therapy	Dietary counseling	Managerial dietitian, nurse
Medication	Medication education	Pharmacist, nurse
Consultation	Smoking cessation education Instruction on stress management, etc.	Nurses Clinical psychologist/licensed psychologist, etc.
	Utilization of social resources	Social worker
Examination	Examination of coronary risk factors CPX	Clinical examination techniques

CPX, cardiopulmonary exercise testing; CR, cardiac rehabilitation.

Exercise training should be instructed by physical therapists or occupational therapists from the acute phase (phase I) to the late recovery phase (phase II), but health exercise instructors are also acceptable for primary prevention and maintenance phase (phase III). However, for primary prevention and the maintenance phase (phase III), a health exercise instructor could serve this role. For patients with HF, a precise exercise prescription is particularly necessary, and the presence of a laboratory technician skilled in exercise stress testing is essential.

The Japanese Society for Cardiac Rehabilitation has established and operated a CR instructor system since 2000 to standardize the knowledge of those involved in CR, such that CR can be performed without being restricted to a specific profession. There are already more than 5,800 certified CR instructors (as of March 2021).

4.3.2 Multidisciplinary Conferences

Regular multidisciplinary conferences are essential for team medicine to function as a high-quality cooperative body that is different from simply a group of professionals. It is desirable that as many professionals as possible, including physicians, nurses, physical therapists, dietitians, pharmacists, clinical psychologists/licensed psychologists, medical social workers, and exercise instructors, participate in the conference. Such a conference should include the following: introduction of new patients, progress reports of patients who have completed the program, information sharing and planning of countermeasures for problematic cases, and consultation on social rehabilitation and mental aspects. Counseling on social rehabilitation and mental health is included, in addition to counseling on cooperation with social welfare services.

As patients become part of the super-aging group, multidisciplinary conferences are becoming more and more important in establishing the future direction. In addition, it is necessary to hold multidisciplinary conferences to discuss the future treatment policy itself, such as considering the presence of multiple diseases, frailty, sarcopenia, and dementia in critically ill patients, and the extent to which they should be treated, and the transition to palliative medicine and home care.

IX. Tele-CR (Table 75)

Table 75. Recommendations and Levels of Evidence for Targeted Tele-CR

	COR	LOE	GOR (MINDS)	LOE (MINDS)
It should be considered to introduce tele-CR to improve the prognosis of cardiac disease	IIa	B	B	II
It should be considered to introduce tele-CR to improve exercise capacity	IIa	B	B	II
It should be considered to introduce tele-CR to improve risk factors for CAD	IIa	B	B	II

CAD, coronary artery disease; COR, class of recommendation; CR, cardiac rehabilitation; GOR, grade of recommendation; LOE, level of evidence.

1. Necessity

The rate of participation in outpatient cardiac rehabilitation (CR) is low worldwide, ranging from 10.3% to 16.3% in patients with coronary artery disease CAD in the USA,⁵¹⁷ ≈50% in patients with CAD in Europe,⁴⁸⁸ and 7% in both inpatient and outpatient CR according to the AMED-CHF study in Japan.¹⁶⁶ A major factor for poor implementation of outpatient CR is access and time barriers to CR facilities.^518–521 In the USA and Europe, home-based CR, in which patients exercise alone at home, has been proposed as an alternative to outpatient CR.^195,418 Furthermore, since 2000, tele-CR based on information and communication technology (ICT), including interactive communication using the Internet and biometric information management, has become widespread.⁵²²

2. Evidence

2.1 Usefulness of Outpatient CR and Tele-CR

In a meta-analysis of 880 patients in 6 randomized controlled trials (RCTs) reported through 2003 comparing home-based CR with center-based supervised CR in patients with CAD, improvements in exercise capacity, systolic blood pressure, and total cholesterol were similar between groups, but quality of life (QOL) was better with home-based CR.⁵²³ In a meta-analysis of 1,938 patients in 12 RCTs reported through 2008 in patients with CAD or heart failure, there were no significant differences in the management of death, reinfarction, revascularization, cardiac readmission, exercise capacity, or risk factors between the home-based and outpatient CR groups.⁵²⁴ A meta-analysis of 17 RCTs including 2,172 patients with CAD or heart failure reported by 2014 showed no significant differences in mortality, cardiac events, exercise capacity, serum lipids, blood pressure, QOL, or medical costs between the home-based and outpatient CR groups, and a slight improvement in adherence in the home-based CR group.⁵²⁵ A meta-analysis of 2,890 patients in 23 RCTs reported through 2016 found no significant differences in mortality, exercise capacity, or QOL between the 2 groups.⁵²⁶

These results suggest that the efficacy and safety of home-based CR is comparable to that of outpatient CR, as long as the cardiac condition and response to exercise stress testing are confirmed and exercise is performed as prescribed.

2.2 Use of Monitoring Devices and Image Communication

Since around the year 2000, the effectiveness of weight control, smoking cessation, and diet and exercise training using ICT for continuing CR has been reported,^527,528 and has been applied to tele-CR.⁵²² RCTs from Europe and the USA reported on comparing home-based CR with outpatient CR using an internet-based ECG waveform monitoring device.^{522,529–531} Although each of the studies included small numbers of patients, there was comparable safety and improvement in physical function between the two groups, and the home-based CR group showed comparable or greater improvement in QOL. In an RCT from Australia, Varnfield et al reported that home-based tele-CR using a smartphone provided blood pressure and weight monitoring, pedometer data, interviews with a supervisor, and educational content, and that the home-based tele-CR group showed a better understanding of CR, better adherence, weight loss, and improved QOL than the outpatient CR group.⁵³²

X. Medical Economic Evaluation

1. Impact on Medical Costs

Two review articles compared the medical costs of cardiac rehabilitation (CR), which adds education and other services to exercise training, with those of usual care, and found that the development of institutional interventions and ancillary programs can reduce costs such as readmissions.^533,534 Seven other papers reported that the implementation of CR or a similar intervention program can reduce healthcare costs in the long term compared with no intervention, although it is not possible to make a general comparison because of differences in program content, evaluation period, and cost calculation items.^535–541 In addition, reports of tele-rehabilitation have increased in recent years, and 1 randomized controlled trial (RCT) reported a reduction in healthcare costs.⁵⁴² Another RCT reported that it is an economical procedure if evaluated over the long term.⁵⁴³

These results suggest that the initial cost of the management program can be recovered in the long run by actively recruiting patients to receive comprehensive CR, and also suggest that long-term CR is effective in preventing recurrence of cardiac disease and may have a significant impact on health insurance finances by optimizing healthcare costs compared with noncompliant patients.

Although there are currently few reports with a high level of evidence in chronic heart failure, there are 2 RCTs including heart failure patients. A recent report of an institutional intervention showed that a 12-week CR (exercise training plus education and counseling) for patients with heart failure, including those with coronary artery disease (CAD) or valve replacement, was not superior in improving health-related quality of life (HRQOL) at 6 months (−0.000 quality-adjusted life years (QALYs), 95% confidence interval (CI) −0.021 to 0.020). However, it tended to reduce social costs (including indirect medical costs) (−1,609 €/person, 95% CI −6,162 to 2,942).

2. Evaluation by Cost-Effectiveness

According to 10 major reports of cost utility analysis (CUA),^540–549 the sample size of the CUAs using QALYs as the outcome measure ranged from 109 to 825 patients. The target diseases were acute coronary syndrome, myocardial infarction, and chronic heart failure, and the CR program was based on exercise training such as treadmill, bicycle ergometer, and walking. In 1 paper,⁵⁴⁰ only exercise training was included, but in the others, education and counseling on risk factors and lifestyle modification were also included in the program to evaluate the effect of comprehensive CR. All control subjects received usual care without CR. All reports were based on RCTs with a high level of evidence, and CR was expected to have a high economic performance if continued for more than 1 year.

Indeed, the systematic review (15 papers) of Papadakis et al⁵³³ and the meta-analysis of Takura et al (5 papers)⁵⁵⁰ also concluded that the procedure was cost effective (cost of US$ 668–16,118 per QALY gained and significant “cost savings and a significant increase in QALYs”). There are an increasing number of reports on tele-intervention as a health economics evaluation of CR. According to 3 CUAs based on RCTs,^542,543,551 comprehensive programs are superior in deploying a combination with institutional interventions on a large scale (and with increased productivity).

Next is cost-effectiveness analysis (CEA), of which there are 6 major reports.^{475,537,552–555} Of these, the 2 with the highest level of evidence^475,554 had total sample sizes of 100–296 patients (NYHA classifications II, III, and IV), including those with chronic heart failure, and the measures of effectiveness were 3-year mortality, survival, and coronary artery stenosis score. They reported that the CR group had a survival advantage over the non-CR group in relation to the required cost.

In addition, a review article⁵⁵⁶ that included educational and counseling interventions and exercise found that the outcomes of HRQOL and prolonged survival relative to cumulative medical costs were superior with CR in terms of long-term prognosis. Improvement in HRQOL was also reported in a meta-analysis of articles.⁵⁵⁷ In addition, 2 recent reports on tele-interventions,^558,559 found that improvements in peak V̇O₂ and cardiovascular risk were cost-effective in combination with institutional interventions and under long-term observation.

Appendix 1. Details of Members

Chairs:

• Shigeru Makita, Department of Cardiac Rehabilitation, Saitama Medical University International Medical Center

• Takanori Yasu (Vice-Chair), Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center

Members:

• Hitoshi Adachi, Department of Cardiology, Gunma Prefectural Cardiovascular Center

• Yoshihiro J Akashi, Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine

• Yoshihiro Fukumoto, Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine

• Yutaka Furukawa, Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital

• Emiko Hasegawa, Faculty of Psychology and Social Welfare, Seigakuin University

• Shunichi Ishihara, Department of Psychology, Bunkyo University Faculty of Human Sciences

• Yoshitaka Iso, Division of Cardiology, Showa University Fujigaoka Hospital

• Hideo Izawa, Department of Cardiology, Fujita Health University of Medicine

• Yutaka Kimura, Department of Health Sciences, Kansai Medical University Hospital

• Shinji Koba, Division of Cardiology, Department of Medicine, Showa University School of Medicine

• Masahiro Kohzuki, Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine

• Akira Koike, Department of Cardiology, Faculty of Medicine, University of Tsukuba

• Shin-ichiro Miura, Department of Cardiology, Fukuoka University School of Medicine

• Masatoshi Nagayama, Department of Cardiovascular Medicine, Sakakibara Heart Institute

• Hideo Ohuchi, Department of Pediatrics, National Cerebral and Cardiovascular Center

• Yusuke Ohya, Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus

• Koichi Okita, Graduate School of Lifelong Sport, Hokusho University

• Kazuto Omiya, Shimazu Medical Clinic

• Masataka Sata, Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences

• Kazunori Shimada, Department of Cardiology, Juntendo University School of Medicine

• Tomoki Shimokawa, Department of Cardiovascular Surgery, Teikyo University

• Hirokazu Shiraishi, Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine

• Naokata Sumitomo, Department of Pediatric Cardiology, Saitama Medical University International Medical Center

• Tetsuya Takahashi, Department of Physical Therapy, Faculty of Health Science, Juntendo University

• Tomoyuki Takura, Department of Healthcare Economics and Health Policy, Graduate School of Medicine, The University of Tokyo

• Hiroyuki Tsutsui, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Sumio Yamada, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine

• Yuichiro Yamada, Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital

• Satoshi Yasuda, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Toshiko Yoshida, College of Nursing, St. Luke’s International University

• Dai Yumino, Yumino Heart Clinic

Collaborators:

• Takuji Adachi, Department of Physical Therapy, Nagoya University Graduate School of Medicine

• Kanta Fujimi, Department of Rehabilitation, Fukuoka University Hospital

• Taiki Higo, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Tasuku Honda, Department of Cardiovascular Surgery, Hyogo Brain and Heart Center

• Toshimi Ikegame, Department of Nursing, Sakakibara Heart Institute

• Takeshi Ishida, Department of Medicine, Saitama Citizens Medical Center

• Kazuhiro P Izawa, Kobe University Graduate School of Health Science

• Naoya Kakutani, Health Link Co., Ltd.

• Kentaro Kamiya, Department of Rehabilitation, School of Allied Health Sciences, Kitasato University

• Yusuke Kasahara, Department of Rehabilitation, St. Marianna University Yokohama Seibu Hospital

• Masaaki Kato, Department of Cardiovascular Surgery, Morinomiya Hospital

• Shintaro Kinugawa, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Yasuyuki Kobayashi, Department of Medical Technology, Gunma Prefectural Cardiovascular Center

• Yuji Kono, Department of Rehabilitation, Fujita Health University Hospital

• Teruyuki Koyama, Department of Rehabilitation, Kameda Medical Center

• Noriko Matsumoto, Department of Nutrition, St. Luke’s International Hospital

• Yasuharu Matsumoto, Department of Cardiovascular Medicine, Shioya Hospital, International University of Health and Welfare

• Ikuko Miyawaki, Department of Nursing, Kobe University Graduate School of Health Sciences

• Makoto Murata, Department of Cardiology, Gunma Prefectural Cardiovascular Center

• Eisaku Nakane, Cardiovascular Center, Kitano Hospital

• Michio Nakanishi, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center

• Mari Nishizaki, Department of Rehabilitation, National Hospital Organization Okayama Medical Center

• Hiroaki Obata, Division of Internal Medicine, Division of Rehabilitation, Niigata Minami Hospital

• Naohiko Osada, Department of Physical Checking, St. Marianna University Toyoko Hospital

• Neiko Ozasa, Cardiovascular Medicine, Kyoto University Hospital

• Kazuhiro Sase, Clinical Pharmacology and Regulatory Science, Graduate School of Medicine, Juntendo University

• Shinji Sato, Department of Physical Therapy, Teikyo Heisei University

• Tatsuhiro Shibata, Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine

• Norio Suzuki, Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine

• Daisuke Tamaki, Department of Nutrition, Showa University Fujigaoka Hospital

• Noboru Watanabe, Department of Cardiology, Hokushin General Hospital

• Shusuke Yagi, Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences

• Midori Yamada, Faculty of Nursing, Kyoritsu Women’s University

• Minako Yamaoka-Tojo, Department of Rehabilitation, School of Allied Health Sciences, Kitasato University

• Masanobu Yanase, Department of Transplantation, National Cerebral and Cardiovascular Center

• Miho Yokoyama, Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine

Independent Assessment Committee:

• Yoichi Goto, Yoka Municipal Hospital

• Ken-Ichi Hirata, Department of Internal Medicine, Kobe University Graduate School of Medicine

• Haruki Ito, Sakakibara Heart Institute

• Takeshi Kimura, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

• Syunei Kyo, Tokyo Metropolitan Geriatric Medical Center

• Ryuji Nohara, Hirakata Kohsai Hospital

(Listed in alphabetical order; affiliations as of March 2021)

Appendix 2. Disclosure of Potential Conflicts of Interest (COI): JCS/JACR 2021 Guideline on Rehabilitation in Patients With Cardiovascular Disease (2018/1/1–2020/12/31)

Author	Member’s own declaration items									COI of the marital partner, first-degree family members, or those who share income and property			COI of the head of the organization/department to which the member belongs (if the member is in a position to collaborate with the head of the organization/department)
	Employer/ leadership position (private company)	Stakeholder	Patent royalty	Honorarium	Payment for manuscripts	Research grant	Scholarship (educational) grant	Endowed chair	Other rewards	Employer/ leadership position (private company)	Stakeholder	Patent royalty	Research grant	Scholarship (educational) grant
Chairs: Shigeru Makita				Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company, Limited Fukuda Denshi Co., Ltd
Chairs: Takanori Yasu						MTG Co., Ltd. Kowa Company, Ltd. AstraZeneca K.K.	Abbott Medical Japan L.L.C
Members: Yoshihiro J Akashi				Daiichi Sankyo Company, Limited		Amgen Astellas BioPharma K.K. Hubit Genomix Inc. National Cerebral and Cardiovascular Center Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company, Limited Mitsubishi Tanabe Pharma Corporation Nippon Boehringer Ingelheim Co., Ltd. Nihon Medi-Physics Co., Ltd.	MC, Inc. Abbott Vascular Japan Co., Ltd. Abbott Medical Japan L.L.C Edwards Lifesciences Corporation Nippon Boehringer Ingelheim Co., Ltd. Nihon Medi-Physics Co., Ltd. Medtronic Japan Co., Ltd. Nihon Kohden Corp. FUJIFILM RI Pharma Co., Ltd. FUJIFILM Toyama Chemical Co., Ltd. Takeda Pharmaceutical Company Limited
Members: Yoshihiro Fukumoto				Actelion Pharmaceuticals Japan Ltd. AstraZeneca K.K. Novartis Pharma K.K. Bayer Yakuhin, Ltd. Janssen Pharmaceutical K.K. Ono Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company, Limited		Alnylam Pharmaceuticals Inc. Actelion Pharmaceuticals Japan Ltd. Daiichi Sankyo Company, Limited Nippon Shinyaku Co., Ltd.	MSD K.K. Astellas Pharma Inc. Abbott Medical Japan L.L.C Eisai Co., Ltd. Novartis Pharma K.K. Bayer Yakuhin, Ltd. Shionogi & Co., Ltd. Kowa Pharmaceutical Co., Ltd. Mochida Pharmaceutical Co., Ltd. Teijin Pharma Limited Japan Lifeline Co., Ltd. Takeda Pharmaceutical Company Limited
Members: Yutaka Furukawa				Daiichi Sankyo Company, Limited Ono Pharmaceutical Co., Ltd. Bayer Yakuhin, Ltd. Novartis Pharma K.K.
Members: Hideo Izawa				Daiichi Sankyo Company, Limited Otsuka Pharmaceutical Co., Ltd. Bristol-Myers Squibb			Takeda Pharmaceutical Company Limited FUJIFILM Toyama Chemical Co., Ltd. Kowa Company, Ltd. Bayer Yakuhin, Ltd. Boston Scientific Japan K.K. Abbott Medical Japan L.L.C BIOTRONIK Japan, Inc.
Members: Yutaka Kimura				Japan Broadcasting Corporation Osaka Medical Association Japan Organization of Occupational Health and Safety AstraZeneca K.K. Daiichi Sankyo Company, Limited Pfizer Japan Inc. Mochida Pharmaceutical Co., Ltd. Novartis Pharma K.K. Astellas Pharma Inc. Mitsubishi Tanabe Pharma Corporation Takeda Pharmaceutical Company Limited	Sekaibunka Holdings								Koga Software Company Total Brain Care Co., Ltd Family Inada Co., Ltd.	Takeda Pharmaceutical Company Limited Astellas Pharma Inc. Daiichi Sankyo Company, Limited Mochida Pharmaceutical Co., Ltd.
Members: Shinji Koba				Pfizer Japan Inc. Kowa Company, Ltd. Takeda Pharmaceutical Company Limited MSD K.K.
Members: Masahiro Kohzuki				Bayer Yakuhin, Ltd. Kyowa Kirin Co., Ltd. Daiichi Sankyo Company, Limited Chugai Pharmaceutical Co., Ltd.	Makino Shuppan IGAKUSHOIN Ltd. Ishiyaku Publishers, Inc.
Members: Shin-ichiro Miura				Bayer Yakuhin, Ltd. Daiichi Sankyo Company, Limited Nippon Boehringer Ingelheim Co., Ltd. Takeda Pharmaceutical Company Limited			Astellas Pharma Inc. Abbott Vascular Japan Co., Ltd. OMRON HEALTHCARE Co., Ltd. HeartFlow Japan G.K. Bayer Yakuhin, Ltd. Sompo Japan Insurance Inc. Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited
Members: Yusuke Ohya				Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited Bayer Yakuhin, Ltd.		KANEKA CORPORATION	Edwards Lifesciences Corporation KANEKA CORPORATION KANEKA MEDIX CORP. Baxter Limited Medtronic Japan Co., Ltd. Japan Lifeline Co., Ltd. Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited
Members: Masataka Sata				Takeda Pharmaceutical Company Limited Bayer Yakuhin, Ltd. Mitsubishi Tanabe Pharma Corporation Daiichi Sankyo Company, Limited Astellas Pharma Inc.		Bayer Yakuhin, Ltd. Daiichi Sankyo Company, Limited Nippon Boehringer Ingelheim Co., Ltd.	Takeda Pharmaceutical Company Limited Mitsubishi Tanabe Pharma Corporation Astellas Pharma Inc. MSD K.K.	Nippon Boehringer Ingelheim Co., Ltd.
Members: Kazunori Shimada				Takeda Pharmaceutical Company Limited Daiichi Sankyo Company, Limited			Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited Roche Diagnostics K.K.
Members: Tomoki Shimokawa							TERUMO CORPORATION Edwards Lifesciences Corporation Abbott Medical Japan L.L.C Japan Lifeline Co., Ltd.
Members: Hirokazu Shiraishi				Medtronic Japan Co., Ltd. Abbott Medical Japan L.L.C Japan Lifeline Co., Ltd.			Medtronic Japan Co., Ltd. Abbott Medical Japan L.L.C
Members: Tetsuya Takahashi													Philips Japan, Ltd. TOHO HOLDINGS CO., LTD.
Members: Tomoyuki Takura								Chugai Pharmaceutical Co., Ltd.
Members: Hiroyuki Tsutsui				AstraZeneca K.K. Novartis Pharma K.K. Bayer Yakuhin, Ltd. Pfizer Japan Inc. Kowa Company, Ltd. Ono Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company, Limited Teijin Pharma Limited Mitsubishi Tanabe Pharma Corporation Nippon Boehringer Ingelheim Co., Ltd.	nippon rinsho Co., Ltd.	IQVIA Services Japan K.K. OMRON HEALTHCARE Co., Ltd. Medical Innovation Kyushu MEDINET Co., Ltd. Daiichi Sankyo Company, Limited Mitsubishi Tanabe Pharma Corporation Japan Tobacco Inc. Nippon Boehringer Ingelheim Co., Ltd.	St.Mary's Hospital Daiichi Sankyo Company, Limited Teijin Pharma Limited Teijin Healthcare Limited Mitsubishi Tanabe Pharma Corporation Nippon Boehringer Ingelheim Co., Ltd.	Actelion Pharmaceuticals Japan Ltd.
Members: Sumio Yamada	PREVENT inc.		MINATO MEDICAL SCIENCE CO., LTD.			MINATO MEDICAL SCIENCE CO., LTD
Members: Satoshi Yasuda				CSL Behring K.K. Bayer Yakuhin, Ltd. Bristol-Myers Squibb Kowa Company, Ltd. Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited		IQVIA Services Japan K.K. JSR Corporation NEC Solution Innovators, Ltd. Actelion Pharmaceuticals Japan Ltd. Abbott Vascular Japan Co., Ltd. Bayer Yakuhin, Ltd. Kowa Company, Ltd. Daiichi Sankyo Company, Limited Takeda Pharmaceutical Company Limited	Abbott Medical Japan L.L.C Amicus Therapeutics, Inc. Bayer Yakuhin, Ltd. Roche Diagnostics K.K. Kowa Company, Ltd. Otsuka Pharmaceutical Co., Ltd. Sumitomo Dainippon Pharma Co., Ltd. Takeda Pharmaceutical Company Limited	Abbott Medical Japan L.L.C Sound Wave Innovation CO., LTD. ZEON MEDICAL INC. Tesco TERUMO CORPORATION Shionogi & Co., Ltd. Kowa Company, Ltd. Mochida Pharmaceutical Co., Ltd. Ono Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Nippon Boehringer Ingelheim Co., Ltd. Medtronic Japan Co., Ltd. Japan Lifeline Co., Ltd. Nihon Kohden Corp. Nippon Shinyaku Co., Ltd. Takeda Pharmaceutical Company Limited
Members: Dai Yumino				Daiichi Sankyo Company, Limited Novartis Pharma K.K.
Collaborators: Kentaro Kamiya				Otsuka Pharmaceutical Factory, Inc. Otsuka Pharmaceutical Co., Ltd. EIKEN Chemical Co., Ltd.		EIKEN Chemical Co., Ltd. SoftBank Corp.	EIKEN Chemical Co., Ltd.
Collaborators: Shintaro Kinugawa								Actelion Pharmaceuticals Japan Ltd.
Collaborators: Eisaku Nakane				Nippon Boehringer Ingelheim Co., Ltd.									Bayer Yakuhin, Ltd.
Collaborators: Tatsuhiro Shibata				Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company,
Collaborators: Minako Yamaoka-Tojo				Bayer Yakuhin, Ltd.	Bayer Yakuhin, Ltd. Mitsubishi Tanabe Pharma Corporation
Independent Assessment Committee: Ken-Ichi Hirata				Kowa Pharmaceutical Co., Ltd. Takeda Pharmaceutical Company Limited		Actelion Pharmaceuticals Japan Ltd. Sysmex Corporation TERUMO CORPORATION Daiichi Sankyo Company, Limited	MSD K.K. Actelion Pharmaceuticals Japan Ltd. Abbott Vascular Japan Co., Ltd. Abbott Medical Japan L.L.C Sanofi K.K. Novartis Pharma K.K. Bayer Yakuhin, Ltd. BIOTRONIK Japan, Inc. Kowa Company, Ltd. Kowa Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Nippon Boehringer Ingelheim Co., Ltd. Nihon Medi-Physics Co., Ltd. Nippon Shinyaku Co., Ltd. FUJIFILM RI Pharma Co., Ltd. FUJIFILM Toyama Chemical Co., Ltd. Takeda Pharmaceutical Company Limited	Abbott Medical Japan L.L.C Sysmex Corporation Medtronic Japan Co., Ltd.
Independent Assessment Committee: Takeshi Kimura				Abbott Vascular Japan Co., Ltd. Sanofi K.K. Bristol-Myers Squibb Boston Scientific Japan K.K. Kowa Company, Ltd. Nippon Boehringer Ingelheim Co., Ltd.		Edwards Lifesciences Corporation EP-CRSU Co., Ltd. Pfizer Japan Inc. Kowa Company, Ltd. Daiichi Sankyo Company, Limited	Astellas Pharma Inc. MID,Inc. Otsuka Pharmaceutical Co., Ltd. Daiichi Sankyo Company, Limited Mitsubishi Tanabe Pharma Corporation Nippon Boehringer Ingelheim Co., Ltd. Takeda Pharmaceutical Company Limited
Independent Assessment Committee: Syunei Kyo		TOBU RAILWAY CO., LTD.								Daiko Jitsugyo, Ltd	TOBU RAILWAY CO., LTD.
Independent Assessment Committee: Ryuji Nohara							NAKAJIMA STEEL PIPE Co., Ltd.

*Notation of corporation is omitted.

*The following persons have no conflict of interest to declare:

Members: Hitoshi Adachi

Members: Emiko Hasegawa

Members: Shunichi Ishihara

Members: Yoshitaka Iso

Members: Akira Koike

Members: Masatoshi Nagayama

Members: Hideo Ohuchi

Members: Koichi Okita

Members: Kazuto Omiya

Members: Naokata Sumitomo

Members: Yuichiro Yamada

Members: Toshiko Yoshida

Collaborators: Takuji Adachi

Collaborators: Kanta Fujimi

Collaborators: Taiki Higo

Collaborators: Tasuku Honda

Collaborators: Toshimi Ikegame

Collaborators: Takeshi Ishida

Collaborators: Kazuhiro P Izawa

Collaborators: Naoya Kakutani

Collaborators: Yusuke Kasahara

Collaborators: Masaaki Kato

Collaborators: Yasuyuki Kobayashi

Collaborators: Yuji Kono

Collaborators: Teruyuki Koyama

Collaborators: Noriko Matsumoto

Collaborators: Yasuharu Matsumoto

Collaborators: Ikuko Miyawaki

Collaborators: Makoto Murata

Collaborators: Michio Nakanishi

Collaborators: Mari Nishizaki

Collaborators: Hiroaki Obata

Collaborators: Naohiko Osada

Collaborators: Neiko Ozasa

Collaborators: Kazuhiro Sase

Collaborators: Shinji Sato

Collaborators: Norio Suzuki

Collaborators: Daisuke Tamaki

Collaborators: Noboru Watanabe

Collaborators: Shusuke Yagi

Collaborators: Midori Yamada

Collaborators: Masanobu Yanase

Collaborators: Miho Yokoyama

Independent Assessment Committee: Yoichi Goto

Independent Assessment Committee: Haruki Ito

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