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Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for Coronary Heart Disease Patients: Study Protocol for a Randomized Controlled Trial ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-036061

Article Type: Protocol

Date Submitted by the 12-Dec-2019 Author:

Complete List of Authors: Ma, Jing; Military General Hospital of Beijing PLA, Department of Cardiovascular Medicine Zhang, Jian; Beijing Normal University, college of P.E and sports Li, Hua; Anzhen Community Health Service Center, Chaoyang District, Department of Cardiovascular Medicine Zhao, Lian; Beijing Shuili Hospital, Department of Cardiovascular Medicine Guo, Ai; Anzhen Community Health Service Center, Chaoyang District, Department of Cardiovascular Medicine Chen, Zai; Beijing Sport University, College of Wushu Yuan, Wen; Beijing Sport University, College of Wushu Gao, Tian; Beijing Normal University, College of Physical Education and Sports http://bmjopen.bmj.com/ Li, Ya; Beijing Normal University, College of Physical Education and Sports Li, Cui; Beijing Sport University, College of Wushu Wang, Hong; Beijing Normal University, College of Physical Education and Sports Song, Bo; Beijing Normal University, College of Physical Education and Sports Lu, Yu; Beijing Normal University; Longyan University

Cui, Mei; Beijing Normal University, College of Physical Education and on October 5, 2021 by guest. Protected copyright. Sports Wei, Qiu; Beijing Normal University, College of Physical Education and Sports Lyu, Shao; Beijing Normal University, College of Physical Education and Sports Yin, Heng; Beijing Normal University, College of Physical Education and Sports

Coronary heart disease < CARDIOLOGY, Health & safety < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Cardiology < INTERNAL Keywords: MEDICINE, Rehabilitation medicine < INTERNAL MEDICINE, MEDICAL EDUCATION & TRAINING, Clinical trials < THERAPEUTICS

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5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 9 I, the Submitting Author has the right to grant and does grant on behalf of all authors of the Work (as defined 10 in the below author licence), an exclusive licence and/or a non-exclusive licence for contributions from authors 11 who are: i) UK Crown employees; ii) where BMJ has agreed a CC-BY licence shall apply, and/or iii) in accordance 12 with the terms applicable for US Federal Government officers or employees acting as part of their official 13 duties; on a worldwide, perpetual, irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its 14 licensees and where the relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the 15 Work in this journal and any other BMJ products and to exploit all rights, as set out in our licence. 16 17 The Submitting Author accepts and understands that any supply made under these terms is made by BMJ to 18 the Submitting Author Forunless you peer are acting as review an employee on behalf only of your employer or a postgraduate 19 student of an affiliated institution which is paying any applicable article publishing charge (“APC”) for Open 20 Access articles. Where the Submitting Author wishes to make the Work available on an Open Access basis (and 21 intends to pay the relevant APC), the terms of reuse of such Open Access shall be governed by a Creative 22 Commons licence – details of these licences and which Creative Commons licence will apply to this Work are set 23 out in our licence referred to above. 24 25 Other than as permitted in any relevant BMJ Author’s Self Archiving Policies, I confirm this Work has not been 26 accepted for publication elsewhere, is not being considered for publication elsewhere and does not duplicate 27 material already published. I confirm all authors consent to publication of this Work and authorise the granting 28 of this licence. 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 i 2 3 4 ID：2019-036061 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Journal：《BMJ Open》 8 9 (1) Article Title： 10 11 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for 12 Coronary Heart Disease Patients: Study Protocol for a Randomized Controlled Trial 13 14 15 16 (2) First-Author 17 18 Jing Ma , Dr For peer review only 19 Military General Hospital of Beijing PLA, 20 Department of Cardiovascular Medicine 21 22 No. 28, Fuxing road, Haidian district, Beijing 23 24 Zip code: 100853 E-mail: [email protected] 25 26 Co- First-Author 27 28 Jianwei Zhang , PhD 29 Beijing Normal University 30 31 College of Physical Education and Sports 32 No.19 Xinjiekou wai street Haidian district, Beijing 33 The People’s Republic of China 34 35 Zip Code: 100875 36 E-mail: [email protected] 37 http://bmjopen.bmj.com/ 38 (3) Co-authors 39 40 Hua Li 41 42 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 43 44 E-mail:[email protected] 45 on October 5, 2021 by guest. Protected copyright. 46 Lianshan Zhao 47 48 Beijing Shuili Hospital, Beijing，China 49 50 E-mail: [email protected] 51 52 53 Aiying Guo 54 55 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 56 57 E-mail: [email protected] 58 59 Zaihao Chen 60

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1 i 2 3 College of Wushu, Beijing Sports University, Beijing, 100084, China. 4

5 E-mail: [email protected] BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Wen Yuan 8 College of Wushu, Beijing Sports University, Beijing, 100084, China. 9 E-mail: [email protected] 10 11 12 Tianming Gao 13 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E- 14 mail:[email protected] 15 16 17 Yameng Li 18 College of P.E. andFor Sports, peer Beijing Normal review University, Beijing,only 100875, China. E-mail: 19 20 [email protected] 21 22 Cuihan Li , Dr 23 College of Wushu, Beijing Sports University, Beijing, 100084, China. 24 25 E-mail:[email protected] 26 27 Hongwei Wang 28 29 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E-mail: 30 [email protected] 31 32 33 Bo Song 34 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E-mail: 35 [email protected] 36 37 http://bmjopen.bmj.com/ 38 Yulong Lu 39 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E-mail: 40 [email protected] 41 42 43 Meize Cui 44 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E-mail: 45 on October 5, 2021 by guest. Protected copyright. 46 [email protected] 47 48 Qiuyang Wei 49 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. E-mail: 50 51 [email protected] 52 53 (4) Corresponding author 54 55 Shaojun Lyu, Ph D 56 Beijing Normal University 57 College of Physical Education and Sports 58 59 No.19 Xinjiekou wai street Haidian district, Beijing 60 The People’s Republic of China

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1 i 2 3 Zip Code: 100875 4

5 E-mail: [email protected] BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Tel：+86 13121860699 8 9 Co -Corresponding author 10 11 Hengchan Yin prof 12 Beijing Normal University 13 14 College of Physical Education and Sports 15 No.19 Xinjiekou wai street Haidian district, Beijing 16 The People’s Republic of China 17 18 Zip Code: 100875For peer review only 19 E-mail: [email protected] 20 21 (5) Keywords 22 23 Coronary heart disease; Complementary medicine; Healthcare; Cardiac rehabilitation; 24 Clinical trials 25 26 (6) Word count: 5103 words 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 i 2 3 4 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Coronary Heart Disease Patients: Study Protocol for a Randomized Controlled 7 8 Trial 9 10 11 INTRODUCTION: Preliminary evidence from clinical observations suggests that Tai 12 13 Chi exercise may offer potential benefits for patients with coronary heart disease (CHD). 14 15 However, the advantages for CHD patients to practice Tai Chi exercise as rehabilitation 16 17 have not been rigorously tested and there is a lack of consensus on its benefits. This 18 For peer review only 19 study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) 20 21 for CHD patients and to assess the efficacy, safety and acceptability of the program. 22 23 24 METHODS AND ANALYSIS: We propose to conduct a multicenter 25 26 randomized‐controlled clinical trial comprising of 150 participants with CHD. The 27 28 patients will be randomly assigned in a 1:1 ratio into either an intervention group or a 29 30 control group. The intervention group will participate in a supervised TCCRP held 3 31 32 times a week for 3 months. The control group will receive supervised conventional 33 34 exercise rehabilitation (CER) held 3 times a week for 3 months. After the 3-month 35 36 intervention period, there will be a 3-month follow-up period with no active 37 http://bmjopen.bmj.com/ 38 intervention in either group. The primary and secondary outcomes will be assessed at 39 40 baseline, 1 month, 3 months and 6 months. Primary outcome measures will include a 41 42 score of 36-Item Short Form Survey (SF-36) and Chinese Perceived Stress Scale 43 44 (CPSS). The secondary outcome measures will include body composition, 45 on October 5, 2021 by guest. Protected copyright. 46 cardiopulmonary exercise test, respiratory muscle function, locomotor skills, 47 48 echocardiogram, New York Heart Association (NYHA) classification, heart rate 49 50 recovery time and laboratory examination. Other measures also include Seattle Angina 51 52 Scale (SAQ), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 53 54 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Berg Balance Scale (BBS), Morse 55 56 Fall Seale (MFS) and Kansas City Cardiomyopathy Questionnaire (KCCQ). All 57 58 adverse events will be recorded and analyzed. Intention-to-treat analysis will be 59 60 performed for participants who withdraw from the trial.

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5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 ETHICS AND DISSEMINATION: This study conforms to the principles of the 7 8 Declaration of Helsinki and relevant ethical guidelines covering informed consent, 9 10 confidentiality and data storage. Ethical approval has been obtained from the Ethics 11 Committee of Chinese PLA General Hospital (approval number S2019-060-02). 12 13 All participants will be fully informed about the trial and will sign a consent form prior 14 15 to participation. Findings from this study will be published and presented at 16 17 conferences for widespread dissemination of the results. 18 For peer review only 19 Trial registration number: ClinicalTrials.gov identifier: NCT03936504 20 21 22 23 STRENGTHENS AND LIMITATIONS OF THE STUDY: 24 25  TCCRP is specifically designed for patients with CHD. 26 27  Tai Chi exercise is easily performed and mastered at home as a cost-free 28 29 rehabilitation program. 30 31  Gentle exercise for CHD patients encourages patient compliance. 32 33  It is difficult to monitor any additional physical activity and accurately track daily 34 35 activity intensity of participants. 36 37  The blinding of participants is unachievable in this trial; however, efforts will be http://bmjopen.bmj.com/ 38 39 made to ensure that the data is blinded. 40 41 42 43 Keywords: Tai Chi, Coronary heart disease, Safety, Effectiveness, Randomized 44 45 controlled trial, Exercise rehabilitation. on October 5, 2021 by guest. Protected copyright. 46 47 48 49 INTRODUCTION 50 Coronary heart disease (CHD) remains the major cause of morbidity and mortality 51 52 worldwide. CHD responsible for about one in every seven deaths; and, CHS is predicted 53 54 to continue until 2030, accounting for 14% of all deaths globally.[1,2] Despite the use 55 56 of effective Western medicine treatments, the incidence of CHD continues to rise and 57 58 is associated with a high mortality rate. While cardiac rehabilitation comprising 59 60 contemporary exercises is recommended for CHD patients, over 60% of CHD patients

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1 i 2 3 4 have been reported to decline current cardiac rehabilitation exercises as they perceive

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 the physical exercise to be unpleasant, painful or impossible to perform in view of their 7 8 conditions.[3] Consequently, there is an unmet need to develop an effective, yet feasible, 9 10 alternative exercise therapy for CHD patients who don’t participate in current cardiac 11 rehabilitation exercises. Furthermore, an effective complementary is needed to be 12 13 developed to improve the functional status and quality of life in CHD patients. 14 15 The integration of Traditional Chinese medicine (TCM) with Western medicine to treat 16 17 CHD has made great progress. As an effective complementary therapy, TCM has been 18 For peer review only 19 demonstrated to improve the prognosis of CHD patients.[4] Tai Chi is an important 20 21 element of TCM which combines the meridians and collateral theory, Yin-Yang theory 22 23 and Five-element theory. The coordinated movement of Tai Chi postures, namely 24 25 “Stirring up Dantian”, “Yi-Qi Cooperation”, “Spiral Silk Reeling” and “Qi Flowing to 26 27 Four Tips (hair, tongue, teeth and bone)” can promote the channeling of Qi and blood 28 29 to nourish the body, resist diseases and promotes immunity. Previous studies have 30 31 shown that regular Tai Chi exercise is beneficial in improving psychological and 32 33 physiological outcomes among CHD patients.[3,5,6] A meta-analysis showed that Tai 34 35 Chi exercise improves left ventricular ejection fraction (LVEF), cardiac output, stroke 36 37 output and reduces resting myocardial oxygen consumption in elderly patients. In http://bmjopen.bmj.com/ 38 39 addition, Tai Chi improves vascular elasticity and promotes the regulation of blood 40 41 pressure, glucose and lipids.[7] 42 43 However, there are many schools in Tai Chi such as the Yang-style, Wu-style, Chen- 44 45 style, Wu-style and Sun-style, wherein each style takes a different approach in terms of on October 5, 2021 by guest. Protected copyright. 46 47 the movements and forms. Furthermore, as Tai Chi exercise comprises many assorted 48 49 movements that can be also complex to perform, it is difficult to popularize and simplify 50 the exercise, especially in elderly patients and patients with chronic diseases. 51 52 Based on prior insights of the Tai Chi movements obtained from our studies and 53 54 other published work,[8,9] our research team developed an innovative TCCRP 55 56 specifically for CHD patients. However, as the value of TCCRP has yet to be clinically 57 58 proven, a clinical trial is required to validate the benefits of adopting this exercise for 59 60 CHD patients.

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1 i 2 3 4 This study aims to assess the efficacy, safety, and acceptability of TCCRP for CHD

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 patients. The primary hypothesis is that TCCRP (the intervention group) will improve 7 8 36-Item Short Form Survey (SF-36), and reduce the score of Chinese Perceived Stress 9 10 Scale (CPSS) when compared against conventional exercise rehabilitation (CER, the 11 control group). Secondary objectives are to evaluate the effects of the TCCRP on body 12 13 composition, cardiopulmonary exercise test, respiratory muscle function, locomotor 14 15 skills, echocardiogram, NYHA classification, heart rate recovery time and laboratory 16 17 examination. Other indicators measured will include SAQ, PSQI, PHQ-9, GAD-7, BBS, 18 For peer review only 19 MFS, KCCQ and major adverse cardiac events. Additional objectives to be explored 20 21 will include: (1) the influence of potential factors on the adherence to the TCCRP; (2) 22 23 the safety of the TCCRP and (3) individual experiences and acceptability following the 24 25 TCCRP. 26 27 28 29 Methods/Design 30 31 Study design 32 33 This is a prospective, multicenter, randomized‐controlled clinical trial comparing a 34 35 TCCRP with CER with an allocation ratio of 1:1. The study period lasts for 6 months 36 37 including a 3-month supervised intervention and a 3-month follow-up with the primary http://bmjopen.bmj.com/ 38 39 outcomes measured at baseline, 1 month, 3 months and 6 months. Secondary outcomes 40 41 will be measured at baseline and after a 3-month intervention period. 42 43 This study is registered on ClinicalTrial.gov (NCT03936504). A brief flowchart of 44 45 the entire study is shown in Figure 1 and the schedule of events is provided in Table 1. on October 5, 2021 by guest. Protected copyright. 46 47 Participants 48 49 Inclusion criteria 50 1. Male or non-pregnant women aged from 18 to 80 years; 51 52 2. Patients who met the criteria for stable angina pectoris in accordance with 53 54 CHD classifications; 55 56 3. NYHA class Ι, Π or Ш; and 57 58 4. Participants who understood the purpose of the clinical trial and voluntarily 59 60 participate with signed informed consent.

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1 i 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Exclusion criteria 7 8 1. Acute myocardial infarction (AMI) within 2 weeks; 9 10 2. Severe aortic stenosis; 11 3. Hypertrophic cardiomyopathy; 12 13 4. Severe valvular heart disease; 14 15 5. Malignant tachyarrhythmia; 16 17 6. Poor patient compliance and incompletion of the clinical trial for not satisfying 18 For peer review only 19 the requirements; 20 21 7. Patients with nervous system deterioration, motor system disease, or 22 23 rheumatic disease caused by combined exercise; 24 25 8. Those who regularly practice Tai Chi during the previous 3 months. 26 27 28 29 Setting and Recruitment 30 31 This multicenter study will be performed at the Beijing Normal University in China. 32 33 Recruitment and exercise training will occur at the Chinese PLA General Hospital, 34 35 China, Beijing Shuili Hospital, China, and Anzhen Community Health Service Center, 36 37 Beijing Chaoyang District, China. One hundred and fifty participants are to be recruited http://bmjopen.bmj.com/ 38 39 and the recruitment is scheduled to begin in October 2019. Combinations of advertising 40 41 strategies include flyers within the hospital, advertisements in the print, online media, 42 43 a major messaging platform (WeChat), clinics and databases. 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 Randomization, allocation concealment and blinding 48 49 After informed consent is signed, all patients will be randomized into either an 50 intervention group receiving a 12-week TCCRP or a control group receiving CER. The 51 52 random allocation sequence will be produced by an independent statistician via the 53 54 PLAN sentences of the statistical software SAS 9.2 in a 1:1 ratio. Next, these 55 56 assignments will be sent to a study staff member, exclusive to the study coordinator or 57 58 principal investigator, who will store them into sealed, opaque envelopes with date and 59 60 signature labels placed over the seals of the envelopes. The randomization envelopes

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1 i 2 3 4 will not be opened unless a participant meets eligibility criteria, completes the informed

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 consent, and undergoes a baseline assessment. The study is conducted in 3 different 7 8 cycles. Each cycle consists of a TCCRP group (intervention group) and CER group 9 10 (control group). Each resulting group consists of 25 patients, equating to a 50 patients 11 participating in each cycle, with a total of 150 patients over the course of the 3 cycles 12 13 comprising the study. The instructors are randomly assigned to the 3 cycles. 14 15 Given the nature of the intervention, it is impossible to blind the patients or any 16 17 personnel who are directly involved in conducting the programs. However, all outcome 18 For peer review only 19 assessors, laboratory technicians, data managers and statisticians will be kept blind of 20 21 the treatment allocations. 22 23 24 25 Patient and Public Involvement 26 27 Involvement of patients and public help us to recognize whether we are doing the right 28 29 thing. Moreover, our research is investigating the impact of different exercise types, 30 31 while irrelevant to any drug or pharmacy corporations, so we can give priority to 32 33 patients as far as possible. During the clinical work of cardiac rehabilitation (CR) 34 35 exercise training, we always take a lot of time to communicate with patients to ask 36 37 about their opinion about coronary artery disease, and about life style therapy and http://bmjopen.bmj.com/ 38 39 exercise training. The patients discussed many times with me whether we could practice 40 41 the Chinese traditional Qigong, such as Baduanjin or TaiChi. Compared with generally 42 43 accepted aerobic exercise, dose TaiChi exhibit better effect? There are few well 44 45 designed clinical trials which could answer the question, so we chose this study to on October 5, 2021 by guest. Protected copyright. 46 47 perform. 48 49 Since the very beginning of our study, we have constructed a Patient Public 50 Involvement group, to let us know what are the things patients think to be most 51 52 important and whether we have done the right study. We choose on purpose the CHD 53 54 patients with different work and different income level. For example, we chose 55 56 government officials, workers, cook, information technology programmer and teachers. 57 58 We held several group meetings, to discuss with them what are the things troubling 59 60 them most now, what do they think about exercise training and TaiChi, and what is the

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1 i 2 3 4 most effective aspect do they think TaiChi would work. We also ask them whether they

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 worry about the safety of exercise, and which kind of exercise do they think is the safest. 7 8 Many patients told us they had heard TaiChi could improve the sleeping disorder and 9 10 insomnia. After the discussion were held, we realized CHD patients care most about 11 how much physical activity is limited, and how to reduce the incidence of angina 12 13 pectoris. Besides, they are willing to try some Chinese traditional Qigong, such as 14 15 Baduanjin or Taichi. So we designed our study to compare the impact of TaiChi and 16 17 traditional exercise training among CHD population. Taken into consideration of what 18 For peer review only 19 the patients care most, to take patients’ priorities and preferences, we chose the 20 21 improvement of cardiopulmonary capacity, score of 36-Item Short Form Survey (SF- 22 23 36) ,sleep quality index and score indicating stress as outcomes. 24 25 We have constructed a Patient Public Involvement group and held the group meeting 26 27 periodically. We discussed with the patients to find out the most important aspect they 28 29 care to be investigated. They also helped us recognize the valuable outcomes to be 30 31 measured. We also contact with them during the conducting period of study to find the 32 33 most effective and convenient way for patients. For the sake of patients, we also 34 35 perform the study at the hospitals, a location familiar to participants. 36 37 Patients were involved a lot in the recruitment to and conduct of the study. During http://bmjopen.bmj.com/ 38 39 the group meeting, Patient Public Involvement group members were informed about 40 41 how the study will be conducted. We also discussed the issue about participant 42 43 recruitment in detail. After the communication, the patients suggested us to prepare 44 45 simple booklet to introduce our study during the outpatients visit and by internet, also on October 5, 2021 by guest. Protected copyright. 46 47 to enlarge the recruitment extent by WeChat and app of our hospital through smart 48 49 mobile phone. The possible difficulties in recruitment were also assessed by the 50 research team and Patient Public Involvement group members together. The possible 51 52 methods were also to be mined. 53 54 The detailed training schedules were also discussed with the group members in order 55 56 to determine the data and time convenient for the patients. Based on the suggestion by 57 58 the patient and public involvement group members, we used ECG monitoring during 59 60 the exercise training. During the study, the patient and public involvement group

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1 i 2 3 4 members were asked periodically if they felt comfortable and able to continue

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 participating. During the study, Patient Public Involvement group members also 7 8 feedback with us whether and when we should extend the rest time. Patient Public 9 10 Involvement group members also helped us explain to the patients what our study is 11 about and the detail of the study in the way patients can understand easier. 12 13 We planed to disseminate our research to the participants and the public, such as 14 15 publicizing our research in hospital official accounts and various academic lectures. At 16 17 the same time, we also recommend that patients in the group send study results to their 18 For peer review only 19 respective friend WeChat groups and family WeChat groups to spread the results 20 21 rapidly. We discussed the way to disseminate findings to study participants with Patient 22 23 Public Involvement group. They suggested us share the results to all the participants 24 25 face to face. By this way, the study researchers could explain the results more clearly 26 27 and instruct them to choose the more effective exercise type. 28 29 They have been informed on detail, and it will be the patients themselves who decides 30 31 whether to take part in or not. We also discussed the study protocol with Patient Public 32 33 Involvement group members. Randomised trial means no one could decide which 34 35 intervention will be delivered to a certain patient. Patient Public Involvement group 36 37 suggested we can teach the participants in control group Tai Chi for free, later after they http://bmjopen.bmj.com/ 38 39 have finished the total study if they want. This will be more grateful for those who longs 40 41 for be randomized to Taichi group. Patient advisers should also be thanked in the 42 43 contributorship statement/acknowledgements. Finally, to measure the burden more 44 45 clearly, we will also ask them to fill in a scale to tell more details about the burden of on October 5, 2021 by guest. Protected copyright. 46 47 the intervention. 48 49 In the end, we have added the acknowledgements to Patient Public Involvement 50 group members for their support for this study. 51 52 53 54 INTERVENTIONS 55 56 Tai Chi cardiac rehabilitation program (TCCRP) group 57 58 Patients in the intervention group will receive TCCRP conducted by a cardiac 59 60 rehabilitation team consisting of cardiologists, cardiology nurses, Tai Chi coaches and

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1 i 2 3 4 research assistants. Procedures and activities of the TCCRP include: (1) Tai Chi

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 exercise, (2) evaluation of exercise ability, (3) education covering topics related to the 7 8 exercise, and (4) a series of adherence strategies. 9 10 11 TCCRP pre-phase: a 2-week exercise before the start of exercise 12 13 1. TCCRP training 14 15 Three professional coaches with at least 5 years of Tai Chi teaching experience will 16 17 be employed to teach and guide the participants’ training. TCCRP will include (a) 18 For peer review only 19 traditional Tai Chi warm-up exercises, followed by (b) Bafa Wubu of Tai Chi, (c)Tai 20 21 Chi elastic belt exercise and (d) Tai Chi cool-down exercises. 22 23 (a) Tai Chi warm-up exercises (10 minutes) will include traditional breathing 24 methods (full-body breathing), weight shifting, arm-swinging etc. These exercises will 25 26 help release tension in the physical body, incorporate mindfulness and imagery into 27 28 movement, increase breathing awareness and promote overall relaxation of the body 29 30 and mind. 31 32 (b) The core Tai Chi movements (30 minutes) will be adapted from the Bafa Wubu 33 34 of Tai Chi (also known as “eight methods and five footwork”, Fig. 2), which include 35 36 introductory routines to Tai Chi characterized with simple structures and rich 37 http://bmjopen.bmj.com/ 38 connotations performed repetitively. Technically speaking, the “Bafa” consists eight 39 40 hand techniques, namely “Peng (warding off), Lu (rolling back), Ji (pressing), An 41 42 (pushing), Cai (pulling down), Lie (splitting), Zhou (elbowing) and Kao (shouldering)”; 43 44 while the “Wubu” consists five footwork, namely “Jin (advancement), Tui (retreat), Gu 45 on October 5, 2021 by guest. Protected copyright. 46 (shifting left), Pan (shifting right) and Ding (central equilibrium). 47 48 (c) Tai Chi combined with light-weight resistance band exercises(10 minutes) will 49 include Tai Chi “Open and Close” movement, Tai Chi Spinning movement and Tai Chi 50 Twining movement. 51 52 (d) Tai Chi cool-down exercises (10 minutes) will include various relaxation methods, 53 54 such as regulating breathing, regulating Qi and regulating mindfullness (Yi).Patients 55 56 are required to practice the TCCRP until they master it. Mastery will be determined by 57 58 the professional coaches. 59 60 2. Evaluation of exercise ability (week − 1 to week 0):

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1 i 2 3 4 (a) Evaluation is conducted by cardiologists and physiotherapists;

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 (b) Evaluation is based on reviewing medical history, cardiopulmonary exercise test 7 8 results and the performance of Tai Chi (heart rate and oxygen consumption will be 9 10 recorded while performing Tai Chi); 11 (c) Evaluation results will guide the goal-setting process during consultation; 12 13 3. Education covering topics related to exercise: 14 15 (a) Basic knowledge of chronic heart disease, 16 17 (b) Basic knowledge of exercise-based cardiac rehabilitation. 18 For peer review only 19 20 21 TCCRP exercise phase: a 12-week intervention period 22 23 Participants will perform the TCCRP 3 times a week for 12 weeks. Each training 24 session is 60 minutes and includes Tai Chi warm-up exercises (10 minutes), Bafa Wubu 25 26 of Tai Chi (30 minutes), Tai Chi combined with light-weight resistance band exercises 27 28 (10 minutes) and Tai Chi cool-down exercises (10 minutes). All participants will be 29 30 encouraged to practice Tai Chi according to an instructional video until the end of the 31 32 12-week period. 33 34 35 36 Researchers will record the subjects’ heart rate and blood pressure before and after 37 http://bmjopen.bmj.com/ 38 training. During the training, the exercise intensity will be assessed by the Borg Rating 39 40 of Perceived Exertion Scale (RPE Scale),[10] which is a frequently used quantitative 41 42 measure of perceived exertion during exercise. 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 TCCRP follow-up phase: a 12-weeek follow-up period 47 48 After the 12-week TCCRP intervention, there will be a 12-week follow-up period that 49 50 excludes any active rehabilitation. During the follow-up period, the participants will be 51 52 asked to fill out forms to record the times and durations of their Tai Chi exercise or 53 54 other physical activities and any incidence of a major adverse cardiac event. The forms 55 56 will be returned to the researchers for follow-up each week by email or WeChat. 57 58 59 60 CER group (Control group)

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1 i 2 3 4 Participants in the control group will receive a CER 3 times a week for 12 weeks. Each

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 training session lasts for 60 minutes, including ordinary warm-up exercises (10 7 8 minutes), aerobic activity (30 minutes), resistive exercise (10 minutes) and cool-down 9 10 exercises (10 minutes). Each training session includes: (1) an active warm-up including 11 arm-swinging, gentle stretches of the neck, shoulders, spine, arms and legs; (2) an 12 13 aerobic activity comprising primarily cycle ergometer exercise; (3) resistive exercise 14 15 mainly including resistance band exercises; and (4) a cool-down session involving 16 17 active and static stretching exercises with primary body movements. 18 For peer review only 19 The CER program is consistent with the current recommended guidelines of 20 21 moderate intensity exercises (50 to 80% Heart Rate Reserve (HRR): Rated Perceived 22 23 Exertion 11–13) for CHD patients. Our program is individually tailored to each 24 25 participant alongside close supervision. The program will be introduced and increased 26 27 in duration and intensity gradually to achieve the target of moderate-intensity exercise. 28 29 30 31 Concomitant treatment 32 33 Participants in both groups will continue routine medications, such as aspirin, 34 35 metoprolol, anti-platelet and anti-coagulant drugs or beta-adrenergic blockers, 36 37 according to patients’ respective conditions and will maintain their usual treatment http://bmjopen.bmj.com/ 38 39 visits throughout the study. All procedures and medication prescriptions will be 40 41 determined by physicians following the clinical guidelines.[11,12] The specific date 42 43 and reasons of any medical therapy changes will be recorded in the case report form 44 45 (CRF). on October 5, 2021 by guest. Protected copyright. 46 47 48 49 Outcome measures 50 All outcome measures will be collected by 3 research assistants at 2 weeks (baseline), 51 52 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month follow- 53 54 up). Demographic information collected will include age, gender, ethnicity, marital 55 56 status, education level, accommodation type and postal address. Clinical information 57 58 will also be obtained from the patients’ clinical records by a member of their hospital 59 60 research team. All data collected from the assistants and therapists will be stored in a

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1 i 2 3 4 dedicated computer for the study and will be kept in a secure and lock-protected

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 location. 7 8 9 10 Primary outcome measures 11 1. The SF-36 Health Survey (SF-36) is a multi-purpose, short-form health survey with 12 13 only 36 questions.[13] SF-36 items cover eight domains: physical functioning, role 14 15 limitations due to physical health problems, body pain, general health, vitality, 16 17 social functioning, role limitations due to emotional problems and mental health. 18 For peer review only 19 Higher scores indicate higher levels of health. SF-36 will be evaluated at baseline, 20 21 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month follow- 22 23 up). 24 25 2. Chinese Perceived Stress Scale (CPSS) is a self-rated questionnaire that assesses 26 27 perceived stress.[14] CPSS consists 14 items that are divided into two categories: 28 29 sense of tension and loss of control. Higher scores indicate higher levels of stress. 30 31 CPSS will be evaluated at baseline, 1 month, 3 months (at the end of intervention) 32 33 and 6 months (at the 3-month follow-up). 34 35 36 37 Secondary outcome measures http://bmjopen.bmj.com/ 38 39 1. Body composition measurements will include fat mass, body fat (percentage), fat- 40 41 free mass and lean body mass. These measurements will be taken by bioelectrical 42 43 impedance analysis using an Inbody 770 (Biospace Co) at baseline, 1 month, 3 44 45 months (at the end of intervention) and 6 months (at the 3-month follow-up). on October 5, 2021 by guest. Protected copyright. 46 47 2. Cardiopulmonary exercise test (CPET) is an objective method being increasingly 48 49 used in a wide spectrum of clinical practice for assessing the functional capacity of 50 CHD patients. Indexes include changes in VO peak and VAT and VE/ VCO slope 51 2 2 52 in the cardiopulmonary exercise test (CPET) at the end of the 3-month intervention. 53 54 3. Respiratory muscle function will be measured by POWER breath K-5. Indexes 55 56 include changes in S-Index, Peak PIF of inspiratory velocity and power at the end 57 58 of the 3-month intervention. 59 60 4. Locomotor skills includes handgrip strength, balance and flexibility. Handgrip

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1 i 2 3 4 strength, which is used to determine the maximum isometric strength of the hand

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 and forearm muscles, will be measured using the handgrip strength dynamometer 7 8 produced by CAMRY (product type EH101). The best result from repeated tests 9 10 of each hand will be recorded. The balance test mainly includes standing on one 11 foot with eyes closed, standing on one foot with eyes open, standing in situ with 12 13 closed eyes and so on. Flexibility will be measured by seated forward flexion test. 14 15 Locomotor skills will be evaluated at baseline and at the end of the 3-month 16 17 intervention. 18 For peer review only 19 5. An echocardiogram comprising LVED Vi and LVEF using echocardiography will 20 21 be assessed at baseline and at the end of the 3-month intervention. NYHA 22 23 classification will also be evaluated at baseline and at the end of the 3-month 24 25 intervention. 26 27 6. Heart rate recovery time will be measured. Heart rate recovery time will record 28 29 heart rate 1 to 6 minutes after Tai Chi exercise, power cycling and resistance 30 31 exercise. 32 33 7. A laboratory examination will be performed that includes glycolipid metabolism, 34 35 inflammatory factor level, immunologic function and oxidative stress index. The 36 37 laboratory examination will be evaluated at baseline and at the end of the 3-month http://bmjopen.bmj.com/ 38 39 intervention. 40 41 8. The Berg Balance Scale (BBS) is a widely used clinical test of a person’s static and 42 43 dynamic balance abilities,[15] and comprises of a set of 14 simple balance related 44 45 tasks, ranging from standing up from a sitting position to standing on one foot. on October 5, 2021 by guest. Protected copyright. 46 47 Total score ranges from 0 to 56, with 0 to 20 corresponding to a high fall risk, 21 48 49 to 40 a medium fall risk and 41 to 56 a low fall risk. The Berg Balance Scale will 50 be evaluated at baseline and at the end of the 3-month intervention. 51 52 9. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that 53 54 assesses sleep quality and disturbances.[16] It contains 19 self-answered questions 55 56 for the subject and 5 peer-answered questions for the bed partner or a roommate (if 57 58 one is available). The scores from seven categories are added to calculate the index, 59 60 ranging from 0 to 21. A score of zero indicates no disturbance in sleep or good

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1 i 2 3 4 sleep quality, whereas higher scores indicate poorer sleep quality. The PSQI will

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 be evaluated at baseline and at the end of the 3-month intervention. 7 8 10. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder- 9 10 7(GAD-7) are validated self-answered questionnaires that assess levels of 11 depression and anxiety. Higher scores reflect greater levels of anxiety and 12 13 depression. PHQ-9 and GAD-7 will be evaluated at baseline and at the end of the 14 15 3-month intervention. 16 17 11. The Seattle Angina Score (SAQ) will be used to determine the total number of 9 18 For peer review only 19 problems and the 5 aspects of CAD, including the degree of physical activity, the 20 21 stability and frequency of angina, the degree of satisfaction of the treatment, and 22 23 the perception of the disease. The higher the score, the better the quality of life and 24 25 body function. SAQ will be measured at baseline and at the end of the 3-month 26 27 intervention. 28 29 12. A record will be made of any side effects and possible adverse reactions arising 30 31 from the intervention. 32 33 34 35 Safety measurements 36 37 All study participants are monitored weekly during the study intervention for the http://bmjopen.bmj.com/ 38 39 occurrence of adverse events defined by any undesirable experience. All adverse events 40 41 that occur during the study will be recorded on the Adverse Event Case Report Form 42 43 and will be evaluated for relevance to the intervention. All adverse events will also be 44 45 reported to the Human Research Committee promptly in accordance with guidelines. on October 5, 2021 by guest. Protected copyright. 46 47 Only patients who are eligible and capable of completing the test will undergo a 48 49 Cardiopulmonary Exercise Test (CPET). For enrolled patients meeting the 50 rehabilitation training standards, they will be stratified according to the degree of 51 52 motion risk and appropriate exercise intensity and time will be adjusted based on their 53 54 risk stratification. Before the cardiac rehabilitation exercise, researchers will educate 55 56 patients about the CHD rehabilitation exercises, including training contraindications 57 58 and exercise advisories regarding the respective CER and TCCRP exercises. Moreover, 59 60 the cardiac rehabilitation Center of Chinese PLA General Hospital, Beijing Shuili

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1 i 2 3 4 Hospital and Anzhen Community Health Service Center are equipped with a

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 comprehensive set of rescue equipment. A thorough contingency plan and rescue 7 8 procedure for cardiovascular events has also been formulated prior to the 9 10 commencement of the research. Should an adverse event occur during the exercise, the 11 researchers will immediately initiate the contingency plan to circumvent the occurrence 12 13 of any fatal outcomes. 14 15 16 17 Data management and monitoring 18 For peer review only 19 Beijing Normal University will be responsible for monitoring research progress, 20 21 managing the data and performing statistical analyses. The research assistants will be 22 23 responsible for checking the integrity of the completed CRF and for timely entry of the 24 25 collected data into the EpiData Manager, a free data management software. The project 26 27 manager will be responsible for initial data cleaning, identifying, coding and converting 28 29 the data into the proper format for analysis. All investigators involved in data 30 31 management and analysis will be blinded to treatment allocation. 32 33 34 35 Statistical analysis 36 37 Continuous variables will be presented as the mean ± standard deviation (SD). Median http://bmjopen.bmj.com/ 38 39 or interquartile range (IQR) and categorical variables will be presented as frequencies 40 41 or percentages. Baseline data between the two groups will be compared and assessed 42 43 using a two-sample Student’s t-test for continuous variables and the chi-square test or 44 45 Wilcoxon test for categorical variables. Questionnaire score data, also known as non- on October 5, 2021 by guest. Protected copyright. 46 47 normally distributed data, will be transformed and analyzed with a nonparametric test. 48 49 We will conduct an intention-to-treat analysis if participants are lost or dropout from 50 the study prior to the follow-up. All data will be analyzed with SPSS 21.0 (IBM, 51 52 Chicago, IL, USA) software packages and Microsoft Excel 2007. Statistical 53 54 significance is defined as a two-sided P value < 0.05. 55 56 57 58 Adherence 59 60 During the 3-month treatment period, participants will be asked to practice strictly

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1 i 2 3 4 according to the training program and will not be allowed to take part in any new or

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 additional exercise programs. Throughout the 3-month intervention period, the 7 8 researchers will track the number of missed sessions for each participant during the 9 10 intervention period. Participants’ attendance will be monitored during each in-person 11 session by staff-completed attendance forms and class sign-in sheets. The percentage 12 13 of compliance will be documented on the case report form. The rate of patient 14 15 compliance = (total planned number of times − number of absence) / total number of 16 17 times × 100%. A compliance rate of 80% or greater will be considered as good, whereas 18 For peer review only 19 a compliance rate of less than 80% is considered as poor. An attendance of less than 20% 20 21 will be considered as a dropout from the study. 22 23 24 25 Discussion 26 27 The development of an ideal and effective cardiac rehabilitation program is still being 28 29 explored and current cardiac rehabilitation mainly consists of contemporary cardio 30 31 exercises. In fact, current cardiac rehabilitation programs have been reported to be 32 33 underdeveloped and limited, reflected by a poor level of involvement with less than 30% 34 35 of patients participating in the existing offerings.[17] As such, there is an unmet need 36 37 for reforms and the provision of alternative cardiac rehabilitation programs to http://bmjopen.bmj.com/ 38 39 encourage the growth of cardiac rehabilitation. The exploration of an ideal cardiac 40 41 rehabilitation exercise that is most beneficial for CHD patients should be determined 42 43 by its complementary effects to the efficacy of existing treatments. 44 45 This trial will be the first to compare the feasibility, safety and benefits of TCCRP on October 5, 2021 by guest. Protected copyright. 46 47 and CER in CHD patients. Compared with conventional exercise styles (e.g. aerobic, 48 49 resistance, and extensibility exercise), Tai Chi typically involves a mind–body 50 integration practice that balances the Yin and Yang in the body, promotes blood 51 52 circulation and Qi for maximizing both physical and mental well-being.[18-20] 53 54 Previous studies have shown that regular Tai Chi exercise is beneficial in improving 55 56 psychological and physiological outcomes among the elderly and various clinical 57 58 populations (e.g. Parkinson’s disease, diabetes mellitus, hypertension, chronic 59 60 obstructive pulmonary disease (COPD) and psychological illness).[21-24] As a typical

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1 i 2 3 4 mind–body exercise which incorporates the characteristics of Traditional Chinese

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Medicine, Tai Chi may be considered to be an effective exercise to promote health in a 7 8 diverse range of populations (e.g. healthy population, patients with chronic diseases, 9 10 youths, middle-aged or elderly adults) [7,25,26,]. 11 At present, many Tai Chi intervention programs differ diversely in terms of their 12 13 duration, style and movements. In fact, some Tai Chi styles and movements can be too 14 15 complex or difficult for older people to learn; and thus, not all Tai Chi styles and 16 17 movements are suitable for patients with CHD. Hence, our research team developed a 18 For peer review only 19 simple and gentle TCCRP that is especially suitable for patients with CHD, whose 20 21 activity tolerance is poor. 22 23 An earlier study reported that over 60% of CHD patients would decline the regular 24 25 cardiac rehabilitation exercise if they perceived the physical exercise to be unpleasant, 26 27 painful or impossible to perform in view of their conditions.[3] In that study, CHD 28 29 patients who declined the regular cardiac rehabilitation, underwent a Tai Chi exercise 30 31 program and were found to be very receptive of the Tai Chi exercise (66% compliance 32 33 rate). In fact, all patients who experienced the Tai Chi rehabilitation program shared 34 35 that they will recommend it to a friend, thereby suggesting a high level of acceptance 36 37 of Tai Chi as a cardiac rehabilitation exercise for patients. Corresponding to the http://bmjopen.bmj.com/ 38 39 objectives of the current proposed study, the previous study by Salmorirago-Blocthcer 40 41 et al. concluded that it is imperative to validate the benefits of Tai Chi in a larger cohort 42 43 of CHD patients in order to develop Tai Chi as an ideal alternative cardiac rehabilitation 44 45 exercise.[3] on October 5, 2021 by guest. Protected copyright. 46 47 There are several strengths of our trial: 1) the proposed research study is unique in 48 49 that the TCCRP is specifically designed for patients with CHD; 2) Tai Chi exercise can 50 be easily performed and mastered at home and is relatively gentle for CHD patients to 51 52 practice thereby encouraging patient compliance. Moreover, if the TCCRP is proved to 53 54 be effective, TCCRP can be a high compliance and cost-free rehabilitation program that 55 56 patients can do at home. This will help save time and costs for CHD patients requiring 57 58 cardiac rehabilitation while potentially reducing social medical expenditure. 59 60 It should be acknowledged that this study has several limitations. It is difficult to

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1 i 2 3 4 monitor any additional physical activity of participants during the study duration.

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Although all participants will be required to record their daily physical activity or 7 8 exercise information with a pedometer, this is not sufficiently accurate to track their 9 10 daily activity intensity. Furthermore, due to the nature of the exercise interventions (Tai 11 Chi versus CER), the blinding of participants is unachievable in this trial. However, 12 13 every effort will be made to ensure that the outcome assessors, data managers and 14 15 statisticians participating in this study will be kept blind of the treatment allocations. 16 17 In conclusion, this study aims to develop an effective TCCRP for CHD patients and 18 For peer review only 19 to explore the safety and effectiveness of TCCRP intervention in CHD patients. The 20 21 results obtained from this trial will be vital to help establish an optimal cardiac 22 23 rehabilitation program for treating CHD patients and will provide reliable evidence for 24 25 the potential application of TCCRP in cardiac rehabilitation. Lastly, the findings from 26 27 this study will also provide relevant understanding for developing a Chinese Tai Chi 28 29 rehabilitation guide to complement existing CHD therapies. 30 31 32 33 Trial status 34 35 This trial began to recruit patients from October 2019. Estimated completion of the trial 36 37 is expected to be completed by December 2020. http://bmjopen.bmj.com/ 38 39 40 41 Additional files 42 43 44 45 Abbreviations on October 5, 2021 by guest. Protected copyright. 46 47 CHD: coronary heart disease; TCCRP: Tai Chi cardiac rehabilitation program; TCM: 48 49 Traditional Chinese Medicine; CER: conventional exercise rehabilitation. 50 51 52 Author affiliations 53 54 1College of Physical Education and Sports, Beijing Normal University, Beijing, China 55 56 2 Department of Cardiovascular Medicine, Military General Hospital of Beijing PLA, 57 58 Beijing, China 59 60 3 Anzhen Community Health Service Center, Chaoyang District, Beijing, China

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1 i 2 3 4 4 Department of Cardiovascular Medicine, Beijing Shuili Hospital, Beijing, China

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 5 6 College of Wushu, Beijing Sports University, Beijing, China 7 8 9 10 Authors’ contributions 11 MJ, LSJ and YHC conceived and designed the study protocol. The individual 12 13 interviews were conducted by MJ, LH, ZLS, and GAY. MJ and ZJW performed the 14 15 translation and analysed the data. ZJW, YW, CZH, WQY, CMZ, LYM, LYL, GTM, 16 17 LCH, SB and WHW guided and supervised the Tai Chi training. MJ and ZJW 18 For peer review only 19 contributed to writing and reading the manuscript. All authors approved the final 20 21 manuscript. 22 23 24 25 Acknowledgements 26 27 The authors most gratefully thank the physicians and nurses of the Chinese PLA 28 29 General Hospital, Beijing Shuili Hospital and Anzhen Community Health Service 30 31 Center, Chaoyang District, Beijing. Thank you for effort working as numbers of Patient 32 33 Public Involvement group, such as Weiling Guo, Wu Feng, Haibin Wang, Yong Ma 34 35 and Jijun Li. 36 37 http://bmjopen.bmj.com/ 38 39 Funding 40 41 This work is financially supported by National Key R&D Program of 42 43 China(2018YFC2000600) and Finance Department of the State Administration of 44 45 Traditional Chinese Medicine (GZY-GCS-2018-011) and the Wushu Research Institute on October 5, 2021 by guest. Protected copyright. 46 47 of the General Administration of Sport of China (WSH2018A004). 48 49 50 Competing interests 51 52 The authors declare that they have no competing interests. 53 54 55 56 Provenance and peer review 57 58 Not commissioned; externally peer reviewed. 59 60

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1 i 2 3 4 Data sharing statement

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 The results of the review will be disseminated through peer-reviewed publications. 7 8 9 10 Open Access 11 This is an open access article distributed in accordance with the Creative Commons 12 13 Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to 14 15 distribute, remix, adapt, build upon this work non-commercially, and license their 16 17 derivative works on different terms, provided the original work is properly cited and 18 For peer review only 19 the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/ 20 21 © Article author(s) (or their employer(s) unless otherwise stated in the text of the 22 23 article) 2019. All rights reserved. No commercial use is permitted unless otherwise 24 25 expressly granted. 26 27 28 29 References 30 31 1. Lozano R, Naghavi M, Foreman K, et al., Global and regional mortality from 235 32 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the 33 Global Burden of Disease Study 2010. Lancet 2012;380:2095-128. 34 35 2. Mirzaei M, Truswell AS, Taylor R, Leeder SR. Coronary heart disease epidemics: 36 not all the same. Heart 2009;95:740-6. 37 3. Salmoirago-Blotcher E, Wayne PM, Dunsiger S, et al. Tai Chi Is a Promising http://bmjopen.bmj.com/ 38 Exercise Option for Patients With Coronary Heart Disease Declining Cardiac 39 40 Rehabilitation. J Am Heart Assoc 2017;6(10). 41 4. Tao T, He T, Wang X, Liu X. Metabolic Profiling Analysis of Patients With 42 Coronary Heart Disease Undergoing Xuefu Zhuyu Decoction Treatment. Front 43 44 Pharmacol 2019;10:985. 45 5. Taylor-Piliae RE, Silva E, Sheremeta SP. Tai Chi as an adjunct physical activity on October 5, 2021 by guest. Protected copyright. 46 for adults aged 45 years and older enrolled in phase III cardiac rehabilitation. Eur 47 48 J Cardiovasc Nurs 2012;11:34-43. 49 6. Sato S, Makita S, Uchida R, Ishihara S, Masuda M. Effect of Tai Chi training on 50 baroreflex sensitivity and heart rate variability in patients with coronary heart 51 disease. Int Heart J 2010;51:238-41. 52 53 7. Liu T, Chan A W, Liu Y H, Taylor-Piliae RE. Effects of Tai Chi-based cardiac 54 rehabilitation on aerobic endurance, psychosocial well-being and cardiovascular 55 risk reduction among patients with coronary heart disease: A systematic review 56 57 and meta-analysis. Eur J Cardiovasc Nurs 2018;17:368-83. 58 8. Jianwei Zhang, Shaojun Lyu, Ji Wang, et al. A comparative study on the 59 therapeutic effect of Taijiquan on patients with type 2 diabetes mellitus of different 60

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1 i 2 3 genders [J]. J Beijing normal University (Nat Sci Ed) 2019;55:545-50 Chinese. 4

5 9. Shaojun Lyu. Bafa Wubu of Tai Chi. Beijing: Beijing Sport University Press. 2018. BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 10. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 7 1982;14:377-81 8 9 11. Fletcher GF, Ades PA, Kligfield P, et al. Exercise standards for testing and training: 10 a scientific statement from the American Heart Association. Circulation 11 2013;128:873-934. 12 12. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from 13 14 theory to practice. A consensus document of the Heart Failure Association and the 15 European Association for Cardiovascular Prevention and Rehabilitation. Eur J 16 Heart Fail 2011;13:347-57. 17 18 13. Ware JE Jr,For Gandek B.peer Overview review of the SF-36 Health only Survey and the International 19 Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol 1998;51:903-12. 20 14. Yang T. Psychological stress of urban population in social transition. Chin J 21 22 Epidemiol 2002;(6):64-6 Chinese. 23 15. Berg K, Wood-Dauphinee S, Williams JI: The balance scale: reliability assessment 24 for elderly residents and patients with an acute stroke. Scand J Rehab Med 25 1995;27:27-36. 26 27 16. Buysse DJ, Reynolds III CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh 28 Sleep Quality Index: a new instrument for psychiatric practice and research. 29 Psychiatry Res 1989;28:193-213. 30 31 17. Gruyter E D, Ford G and Stavreski B. Economic and Social Impact of Increasing 32 Uptake of Cardiac Rehabilitation Services – A Cost Benefit Analysis. Heart Lung 33 Circ 2016;25:175-83. 34 35 18. Nery RM, Zanini M, Ferrari JN, et al., Tai Chi Chuan for cardiac rehabilitation in 36 patients with coronary arterial disease. Arq Bras Cardiol 2014;102:588-92. 37 19. Yang YL, Wang YH, Wang, SR, Shi PS, Wang C. The Effect of Tai Chi on http://bmjopen.bmj.com/ 38 Cardiorespiratory Fitness for Coronary Disease Rehabilitation: A Systematic 39 40 Review and Meta-Analysis. Front Physiol 2018;8:1091. 41 20. Lan C, Chen SY, Lai JS, Wong MK. The effect of Tai Chi on cardiorespiratory 42 function in patients with coronary artery bypass surgery. Med Sci Sports Exerc 43 44 1999;31:634-8. 45 21. Chang RY, Koo M, Yu ZR, et al. The effect of Tai Chi exercise on autonomic on October 5, 2021 by guest. Protected copyright. 46 nervous function of patients with coronary artery disease. J Altern Complement 47 48 Med 2008;14:1107-13. 49 22. Gao Q, Leung A, Yang Y, et al. Effects of Tai Chi on balance and fall prevention 50 in Parkinson's disease: a randomized controlled trial. Clin Rehabil 2014;28:748- 51 53. 52 53 23. Xiao CM, Zhuang YC. Effects of Tai Chi ball on balance and physical function 54 in older adults with type 2 diabetes mellitus. J Am Geriatr Soc 2015;63):176-7. 55 24. Chan AW, Lee A, Lee DT, et al. The sustaining effects of Tai chi Qigong on 56 57 physiological health for COPD patients: a randomized controlled trial. 58 Complement Ther Med 2013;21:585-94. 59 25. Chen WW, Sun WY. Tai chi chuan, an alternative form of exercise for health 60

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1 i 2 3 promotion and disease prevention for older adults in the community. Int Q 4

5 Community Health Educ 1996;16:333-9. BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 26. Guo JB, Chen BL, Lu YM, et al. Tai Chi for improving cardiopulmonary function 7 and quality of life in patients with chronic obstructive pulmonary disease: a 8 9 systematic review and meta-analysis. Clin Rehabil 2016;30:750-64. 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 i 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Table 1: Schedule for data collection; outcome measures per visits 7 8 Phase 9 Phase Ι: Phase Π: Phase Ш: Phase Ⅳ: 10 Items Ⅴ: 11 Screening Baseline Month 1 Month 3 12 Month 6 13 14 Inclusion/exclusion criteria √ 15 16 17 Diagnostic index √ 18 For peer review only 19 Signed informed consent √ 20 21 22 Randomization and allocation √ 23 24 Safety index √ √ √ √ 25 26 27 General clinical information √ √ 28 29 30 Primary outcomes √ √ 31 32 Secondary outcomes √ √ 33 34 35 Other indicators √ √ 36 37 http://bmjopen.bmj.com/ Recurrent cardiovascular events √ √ √ 38 39 40 Adherence √ √ √ 41 42 43 Adverse events √ √ 44 45 Summary at the end of the study √ on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 i 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 Figure 1: Flow diagram of study design 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 Figure. 2: Exemplary Bafa Wubu of Tai Chi; the pictures have taken the portrait right; 58 the fugleman is the developer of TCCRP. 59 60

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Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for Chronic Coronary Syndrom Patients: Study Protocol for a Randomized Controlled Trial ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-036061.R1

Article Type: Protocol

Date Submitted by the 19-Feb-2020 Author:

Primary Subject Sports and exercise medicine Heading:

Complementary medicine, Cardiovascular medicine, General practice / Secondary Subject Heading: Family practice, Rehabilitation medicine, Evidence based practice

Coronary heart disease < CARDIOLOGY, SPORTS MEDICINE, COMPLEMENTARY MEDICINE, EDUCATION & TRAINING (see Medical Keywords: Education & Training), REHABILITATION MEDICINE, Clinical trials < THERAPEUTICS

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1 2 3 4

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1 2 3 4 ID：2019-036061 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Journal：《BMJ Open》 8 9 (1) Article Title： 10 11 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for Chronic 12 Coronary Syndrom Patients: Study Protocol for a Randomized Controlled Trial 13 14 15 16 (2) First-Author 17 18 Jing Ma , Dr For peer review only 19 Department of Cardiology 20 First Medical Center of Chinese People’s Libration Army General Hospital, 21 22 No. 28, Fuxing road, Haidian district, Beijing 23 24 Zip code: 100853 E-mail: [email protected] 25 26 Co- First-Author 27 28 Jianwei Zhang , PhD 29 Beijing Normal University 30 31 College of Physical Education and Sports 32 No.19 Xinjiekou wai street Haidian district, Beijing 33 The People’s Republic of China 34 35 Zip Code: 100875 36 E-mail: [email protected] 37 http://bmjopen.bmj.com/ 38 (3) Co-authors 39 40 Hua Li 41 42 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 43 44 E-mail:[email protected] 45 on October 5, 2021 by guest. Protected copyright. 46 Lianshan Zhao 47 48 Beijing Shuili Hospital, Beijing，China 49 50 E-mail: [email protected] 51 52 53 Aiying Guo 54 55 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 56 57 E-mail: [email protected] 58 59 Zaihao Chen 60 1

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1 2 3 College of Wushu, Beijing Sports University, Beijing, 100084, China. 4

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1 2 3 The People’s Republic of China 4

5 Zip Code: 100875 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 E-mail: [email protected] 7 8 Tel：+86 13121860699 9 10 11 Co -Corresponding author 12 Hengchan Yin prof 13 14 Beijing Normal University 15 College of Physical Education and Sports 16 No.19 Xinjiekou wai street Haidian district, Beijing 17 18 The People’s RepublicFor of peer China review only 19 Zip Code: 100875 20 E-mail: [email protected] 21 22 (5) Keywords 23 24 Coronary heart disease; Complementary medicine; Healthcare; Cardiac rehabilitation; 25 Clinical trials 26 27 28 (6) Word count: 4762 words 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3

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1 2 3 4 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Chronic Coronary Syndrom Patients: Study Protocol for a Randomized 7 8 Controlled Trial 9 ABSTRACT 10 11 Introduction: Preliminary evidence from clinical observations suggests that Tai Chi 12 13 exercise may offer potential benefits for patients with chronic coronary syndrom(CCS). 14 However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation 15 16 have not been rigorously tested and there is a lack of consensus on its benefits. This 17 18 study aims to developFor an peerinnovative Taireview Chi Cardiac Rehabilitation only Program (TCCRP) 19 for CCS patients and to assess the efficacy, safety and acceptability of the program. 20 21 22 23 Methods and analysis: We propose to conduct a multicenter randomized‐controlled 24 25 clinical trial comprising of 150 participants with CCS. The patients will be randomly 26 assigned in a 1:1 ratio into two groups. The intervention group will participate in a 27 28 supervised TCCRP held 3 times a week for 3 months. The control group will receive 29 30 supervised conventional exercise rehabilitation (CER) held 3 times a week for 3 months. 31 32 The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months 33 after intervention and after an additional 3 months follow-up period. Primary outcome 34 35 measures will include a score of 36-Item Short Form Survey and Chinese Perceived 36 37 Stress Scale. The secondary outcome measures will include body composition, http://bmjopen.bmj.com/ 38 cardiopulmonary exercise test, respiratory muscle function, locomotor skills, 39 40 echocardiogram, New York Heart Association classification, heart rate recovery time 41 42 and laboratory examination. Other measures also include Seattle Angina Scale, 43 44 Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety on October 5, 2021 by guest. Protected copyright. 45 Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analyzed. 46 47 48 49 Ethics and dissemination: This study conforms to the principles of the Declaration of 50 51 Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the 52 Ethics Committee of Chinese PLA General Hospital (approval number S2019-060-02). 53 54 Findings from this study will be published and presented at conferences for widespread 55 56 dissemination of the results. 57 58 59 Trial registration number: ClinicalTrials.gov identifier: NCT03936504 60 4

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1 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Strengths and limitations of this study: 7 8  The proposed research study is unique and the first study about a Bafa Wubu of 9 10 Tai Chi which is a new Tai Chi school. 11 12  TCCRP in this study was specifically designed for patients with CCS. 13  This is the first time for Tai Chi study to develop a comparative training system 14 15 to match the conventional exercise. 16 17  It is difficult to exclude the effect of other physical activity due to difficulty of 18 For peer review only 19 monitoring. 20 21  The blinding of participants is unachievable in this trial; however, efforts will be 22 made to ensure that the data is blinded. 23 24 25 26 Keywords: Tai Chi, Coronary heart disease, Chronic coronary syndrom, Safety, 27 28 Effectiveness, Randomized controlled trial, Exercise rehabilitation. 29 30 31 32 INTRODUCTION 33 Coronary heart disease (CHD) remains the major cause of morbidity and mortality 34 35 worldwide. CHD responsible for about one in every seven deaths; and, China Heart 36 1 37 Society is predicted to continue until 2030, accounting for 14% of all deaths globally. http://bmjopen.bmj.com/ 38 2 Despite the use of effective Western medicine treatments, the incidence of CHD 39 40 continues to rise and is associated with a high mortality rate. Cardiac rehabilitation (CR), 41 42 especially exercise training is proven to significantly alleviate the cardiac symptoms, 43 44 preserve the heart function, and improve the clinical outcomes. Therefore cardiac 45 rehabilitation is recommended by many guidelines of different countries.3-9 However, on October 5, 2021 by guest. Protected copyright. 46 47 latest study demonstrated only 24.4% CR-eligible Medicare beneficiaries participated 48 10 49 in CR and marked disparities were observed. Besides limitation of medical resource, 50 poor compliance of patients remains main reason. An effective and attractive CR 51 52 training system is urgently needed. 53 54 These years the integration of Traditional Chinese medicine (TCM) with Western 55 56 medicine to treat CHD has made great progress. As an effective complementary therapy, 57 58 TCM has been demonstrated to improve the prognosis of CHD patients.11 Tai Chi is an 59 60 5

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1 2 3 4 important element of TCM which combines the meridians and collateral theory, Yin-

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Yang theory and Five-element theory. Tai Chi exercise contains three core elements, 7 8 namely “body”, “breath” and “mind”, as pronounced in Chinese as “Xing”, “Qi”, “Yi” 9 10 respectively. The spirits of Tai Chi are summarized to “building the body”, “conveying 11 the breath” and “using the mind”. Previous studies have shown that regular Tai Chi 12 13 exercise was beneficial in improving psychological and physiological outcomes among 14 15 CHD patients.12-15 Study by Professor Salmorirago-Blocthcer have showed patients 16 17 receiving Tai Chi exercise exhibited much better compliance than those receiving 18 For peer review only 19 conventional exercise. 12 20 21 There are many schools in Tai Chi such as the Yang-style, Wu-style, Chen-style, 22 23 Wu-style and Sun-style, wherein each style takes a different approach in terms of the 24 25 movements and forms. Furthermore, as Tai Chi exercise comprises many assorted 26 27 movements that can be also complex to perform, it is difficult to popularize and simplify 28 29 the exercise, especially in elderly patients and patients with chronic diseases. 30 31 Based on prior insights of the Tai Chi movements obtained from our studies and 32 33 other work,16 17 our research team developed an innovative Tai Chi Cardiac 34 35 Rehabilitation Program (TCCRP) specifically for CHD patients. However, as the value 36 37 of TCCRP has not yet to be clinically proven, a clinical trial is required to validate the http://bmjopen.bmj.com/ 38 39 benefits of adopting this exercise for CHD patients. 40 CHD can be categorized as either acute coronary syndrome (ACS) or chronic 41 42 coronary syndrome (CCS) due to pathophysiological features and clinical prognosis 43 44 because it is dynamic process of atherosclerotic plaque accumulation and functional on October 5, 2021 by guest. Protected copyright. 45 18 46 alterations of coronary circulation . Between the two process, most CHD patients stay 47 in the CCS state. Latest studies revealed patients with CCS benefit a lot from cardiac 48 49 rehabilitation programs characterized by life style therapy18. So we chose CCS patients 50 51 as our subjects. This study aims to assess the efficacy, safety, and acceptability of 52 TCCRP for CCS patients. 53 54 55 The primary hypothesis is that TCCRP (the intervention group) will improve the life 56 quality and reduce the stress when compared against conventional exercise 57 58 rehabilitation (CER, the control group). Secondary objectives are to evaluate the effects 59 60 6

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1 2 3 4 of the TCCRP on body composition, cardiopulmonary exercise test, respiratory muscle

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 function, locomotor skills, echocardiogram, New York Heart Association (NYHA) 7 8 classification, heart rate recovery time and laboratory examination. Other indicators 9 10 measured will include Seattle Angina Scale (SAQ), Pittsburgh Sleep Quality Index 11 (PSQI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 12 13 (GAD-7), Berg Balance Scale (BBS) and major adverse cardiac events. Additional 14 15 objectives to be explored will include: (1) the influence of potential factors on the 16 17 adherence to the TCCRP; (2) the safety of the TCCRP and (3) individual experiences 18 For peer review only 19 and acceptability following the TCCRP. 20 21 22 23 METHODS/DESIGN 24 25 Study design 26 27 This is a prospective, multicenter, randomized‐controlled clinical trial comparing a 28 29 TCCRP with CER with an allocation ratio of 1:1. The study period lasts for 6 months 30 31 including a 3-month supervised intervention and a 3-month follow-up with the primary 32 33 outcomes measured at baseline, 1 month, 3 months and 6 months. Secondary outcomes 34 35 will be measured at baseline and after a 3-month intervention period. 36 37 This study is registered on ClinicalTrial.gov (NCT03936504). A brief flowchart of http://bmjopen.bmj.com/ 38 39 the entire study is shown in Figure 1 and the schedule of events is provided in Table 1. 40 41 42 43 Sample size calculation 44 45 Sample size calculation will be based on the co-primary outcomes of the RCT. The SF- on October 5, 2021 by guest. Protected copyright. 46 47 36 Health Survey (SF-36) and Chinese Perceived Stress Scale (CPSS) are being set as 48 49 the co-primary outcome and used for sample size calculation. Sample size was 50 calculated on the basis of the changes in the SF-36 and CPSS between comparison 51 52 groups with a significance level of 5% and a two-tailed critical region to ensure the 53 54 same effect size with 80% power by G*power V.3.1.9.4 software. The means and their 55 56 SDs (mean ±SD) of the SF-36 and CPSS in the control and intervention group were 57 58 (64.30±13.11, 71.79±16.03)19 and (42.31±8.17, 35.15±6.82)20, respectively, at 59 60 7

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1 2 3 4 postintervention according to the published literature. Because the sample size

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 calculation of CPSS was less than SF-36, the sample size calculation of SF-36 was 7 8 selected. This would require 122 participants, inflated to about 150 to account for the 9 10 loss to follow-up of approximately 20% of participants, with 75 participants being 11 assigned to each group. 12 13 14 15 Participants 16 17 Inclusion criteria 18 For peer review only 19 1. Male or non-pregnant women aged from 18 to 80 years; 20 21 2. Patients who met the diagnosis criteria of chronic coronary syndrome included 22 23 in18; 24 25 3. NYHA class Ι, Π; 26 27 4. Participants who understood the purpose of the clinical trial and voluntarily 28 29 participate with signed informed consent. 30 31 32 33 Exclusion criteria 34 35 1. Acute myocardial infarction (AMI) within 2 weeks; 36 37 2. Severe aortic stenosis; http://bmjopen.bmj.com/ 38 39 3. Hypertrophic cardiomyopathy; 40 41 4. Severe valvular heart disease; 42 43 5. Malignant tachyarrhythmia; 44 45 6. Poor patient compliance and incompletion of the clinical trial for not satisfying on October 5, 2021 by guest. Protected copyright. 46 47 the requirements; 48 49 7. Patients with abnormal motor function caused by nervous system deterioration, 50 motor system disease or rheumatic disease; 51 52 8. Those who regularly practice Tai Chi during the previous 3 months. 53 54 55 56 Setting and Recruitment 57 58 This multicenter study will be performed at the Beijing Normal University in China. 59 60 8

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1 2 3 4 Recruitment and exercise training will occur at the Chinese PLA General Hospital,

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 China, Beijing Shuili Hospital, China, and Anzhen Community Health Service Center, 7 8 Beijing Chaoyang District, China. One hundred and fifty participants are to be recruited 9 10 and the recruitment is scheduled to begin in October 2019. Combinations of advertising 11 strategies include flyers within the hospital, advertisements in the print, online media, 12 13 a major messaging platform (WeChat), clinics and databases. 14 15 16 17 Randomization, allocation concealment and blinding 18 For peer review only 19 After informed consent is signed, all patients will be randomized into either an 20 21 intervention group receiving a 12-week TCCRP or a control group receiving CER. The 22 23 random allocation sequence will be produced by an independent statistician via the 24 25 PLAN sentences of the statistical software SAS 9.2 in a 1:1 ratio. Next, these 26 27 assignments will be sent to a study staff member, exclusive to the study coordinator or 28 29 principal investigator, who will store them into sealed, opaque envelopes with date and 30 31 signature labels placed over the seals of the envelopes. The randomization envelopes 32 33 will not be opened unless a participant meets eligibility criteria, completes the informed 34 35 consent, and undergoes a baseline assessment. The study is conducted in 3 different 36 37 cycles. Each cycle consists of a TCCRP group (intervention group) and CER group http://bmjopen.bmj.com/ 38 39 (control group). Each resulting group consists of 25 patients, equating to a 50 patients 40 41 participating in each cycle, with a total of 150 patients over the course of the 3 cycles 42 43 comprising the study. The instructors are randomly assigned to the 3 cycles. 44 45 Given the nature of the intervention, it is impossible to blind the patients or any on October 5, 2021 by guest. Protected copyright. 46 47 personnel who are directly involved in conducting the programs. However, all outcome 48 49 assessors, laboratory technicians, data managers and statisticians will be kept blind of 50 the treatment allocations. 51 52 53 54 Patient and Public Involvement 55 56 We gave priority to patients as far as possible. Patients are the major factor to be 57 58 consider when designing the trial, subject recruitment and data sharing. Since the very 59 beginning of our study, we have constructed a Patient Public Involvement group. 60 9

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1 2 3 During the group meeting, Patient Public Involvement group members were informed 4

5 about how the study will be conducted. We always take a lot of time to communicate BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 with patients about how to improve the detail of study to improve their compliance and 8 they have given some good advice. For example, the patients suggested us to prepare 9 10 simple booklet to introduce our study during the outpatients visit and by internet, also 11 12 to enlarge the recruitment extent by WeChat and app of our hospital. We planned to 13 14 disseminate our research to the participants and the public, such as publicizing our 15 research in hospital official accounts and various academic lectures. 16 17 18 For peer review only 19 Interventions 20 21 Tai Chi cardiac rehabilitation program (TCCRP) group 22 23 Patients in the intervention group will receive TCCRP conducted by a cardiac 24 25 rehabilitation team consisting of cardiologists, cardiology nurses, Tai Chi coaches and 26 27 research assistants. Procedures and activities of the TCCRP include: (1) Tai Chi 28 29 exercise, (2) evaluation of exercise ability, (3) education covering topics related to the 30 31 exercise, and (4) a series of adherence strategies. 32 33 34 35 TCCRP pre-phase: a 2-week exercise before the start of exercise 36

1. TCCRP training http://bmjopen.bmj.com/ 37 38 Six professional coaches with at least 10 years of Tai Chi teaching experience will 39 40 be employed to teach and guide the participants’ training. TCCRP will include (a) 41 42 traditional Tai Chi warm-up exercises, followed by (b) Bafa Wubu of Tai Chi, (c)Tai 43 44 Chi elastic belt exercise and (d) Tai Chi cool-down exercises. 45 on October 5, 2021 by guest. Protected copyright. 46 (a) Tai Chi warm-up exercises (10 minutes) will include traditional breathing 47 48 methods (full-body breathing), weight shifting, arm-swinging etc. These exercises will 49 50 help release tension in the physical body, incorporate mindfulness and imagery into 51 52 movement, increase breathing awareness and promote overall relaxation of the body 53 54 and mind. 55 56 (b) The core Tai Chi movements (30 minutes) will be adapted from the Bafa Wubu 57 58 of Tai Chi (also known as “eight methods and five footwork”, Fig. 2), which include 59 60 introductory routines to Tai Chi characterized with simple structures and rich 10

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1 2 3 4 connotations performed repetitively. Technically speaking, the “Bafa” consists eight

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 hand techniques, namely “Peng (warding off), Lu (rolling back), Ji (pressing), An 7 8 (pushing), Cai (pulling down), Lie (splitting), Zhou (elbowing) and Kao (shouldering)”; 9 10 while the “Wubu” consists five footwork, namely “Jin (advancement), Tui (retreat), Gu 11 (shifting left), Pan (shifting right) and Ding (central equilibrium). 12 13 (c) Tai Chi combined with light-weight resistance band exercises(10 minutes) will 14 15 include Tai Chi “Open and Close” movement, Tai Chi Spinning movement and Tai Chi 16 17 Twining movement. 18 For peer review only 19 (d) Tai Chi cool-down exercises (10 minutes) will include various relaxation methods, 20 21 such as regulating breath, regulating body and regulating mind. 22 23 Patients are required to practice the TCCRP until they master it. Mastery will be 24 25 determined by the professional coaches. The mastery of Tai Chi was assessed and 26 27 quantified due to the following 6 factors: the body shape should keep straight and 28 29 upright; the gravity center shift is right; the action moves in an order; moving speed has 30 31 a sense of rhythm; action and movement contains wring and screwing; every set 32 33 consumes similar time. We have constructed a testing committee including 10 Tai Chi 34 35 exports who had discussed together and summerized a scoring criteria concerning the 36 37 above 6 dimensions. Six professional coaches with more than 10 years of Tai Chi http://bmjopen.bmj.com/ 38 39 teaching experiences were trained about the scoring system and then coached the 40 41 subjects. At the end of learning stage, 3 of coaches were chosen randomly to work as 42 43 the examiner. The professional coaches scored on a percentile basis according to the 44 45 above 6 dimensions. Only the participants who gained an average score higher than 80 on October 5, 2021 by guest. Protected copyright. 46 47 would be certificated to be qualified and move on the to the trial step. 48 49 2. Evaluation of exercise ability (week − 1 to week 0): 50 (a) Evaluation is conducted by cardiologists and physiotherapists; 51 52 (b) Evaluation is based on reviewing medical history, cardiopulmonary exercise test 53 54 results and the performance of Tai Chi (heart rate and oxygen consumption will be 55 56 recorded while performing Tai Chi); 57 58 (c) Evaluation results will guide the goal-setting process during consultation; 59 60 11

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1 2 3 3. Education covering topics related to exercise: 4

5 (a) Basic knowledge of chronic heart disease, BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 (b) Basic knowledge of exercise-based cardiac rehabilitation. 8 9 10 11 TCCRP exercise phase: a 12-week intervention period 12 13 Participants will perform the TCCRP 3 times a week for 12 weeks. Each training 14 15 session is 60 minutes and includes Tai Chi warm-up exercises (10 minutes), Bafa Wubu 16 17 of Tai Chi (30 minutes), Tai Chi combined with light-weight resistance band exercises 18 For peer review only 19 (10 minutes) and Tai Chi cool-down exercises (10 minutes). All participants will be 20 21 encouraged to practice Tai Chi according to an instructional video until the end of the 22 23 12-week period. 24 25 26 Researchers will record the subjects’ heart rate and blood pressure before and after 27 28 training. During the training, the exercise intensity will be assessed by the Borg Rating 29 30 of Perceived Exertion Scale (RPE Scale),21 which is a frequently used quantitative 31 32 measure of perceived exertion during exercise. 33 34 35 36 TCCRP follow-up phase: a 12-weeek follow-up period 37 http://bmjopen.bmj.com/ 38 After the 12-week TCCRP intervention, there will be a 12-week follow-up period that 39 40 excludes any active rehabilitation. During the follow-up period, the participants will be 41 42 asked to fill out forms to record the times and durations of their Tai Chi exercise or 43 44 other physical activities and any incidence of a major adverse cardiac event. The forms 45 on October 5, 2021 by guest. Protected copyright. 46 will be returned to the researchers for follow-up each week by email or WeChat. 47 48 49 50 CER group (Control group) 51 52 Participants in the control group will receive a CER 3 times a week for 12 weeks. Each 53 54 training session lasts for 60 minutes, including ordinary warm-up exercises (10 55 56 minutes), aerobic activity (30 minutes), resistive exercise (10 minutes) and cool-down 57 58 exercises (10 minutes). Each training session includes: (1) an active warm-up including 59 60 12

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1 2 3 4 arm-swinging, gentle stretches of the neck, shoulders, spine, arms and legs; (2) an

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 aerobic activity comprising primarily cycle ergometer exercise; (3) resistive exercise 7 8 mainly including resistance band exercises; and (4) a cool-down session involving 9 10 active and static stretching exercises with primary body movements. 11 The CER program is consistent with the current recommended guidelines of 12 13 moderate intensity exercises (50 to 80% Heart Rate Reserve (HRR): Rated Perceived 14 15 Exertion 11–13) for CHD patients. Our program is individually tailored to each 16 17 participant alongside close supervision. The program will be introduced and increased 18 For peer review only 19 in duration and intensity gradually to achieve the target of moderate-intensity exercise. 20 21 22 23 Concomitant treatment 24 25 Participants in both groups will continue routine medications, such as aspirin, 26 27 metoprolol, anti-platelet and anti-coagulant drugs or beta-adrenergic blockers, 28 29 according to patients’ respective conditions and will maintain their usual treatment 30 31 visits throughout the study. All procedures and medication prescriptions will be 32 33 determined by physicians following the clinical guidelines.22 23 The specific date and 34 35 reasons of any medical therapy changes will be recorded in the case report form (CRF). 36 37 http://bmjopen.bmj.com/ 38 39 Outcome measures 40 41 All outcome measures will be collected by 3 research assistants at 2 weeks (baseline), 42 43 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month follow- 44 45 up). Demographic information collected will include age, gender, ethnicity, marital on October 5, 2021 by guest. Protected copyright. 46 47 status, education level, accommodation type and postal address. Clinical information 48 49 will also be obtained from the patients’ clinical records by a member of their hospital 50 research team. All data collected from the assistants and therapists will be stored in a 51 52 dedicated computer for the study and will be kept in a secure and lock-protected 53 54 location. 55 56 57 58 Primary outcome measures 59 60 13

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1 2 3 4 1. The SF-36 Health Survey (SF-36) is a multi-purpose, short-form health survey with

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 24 6 only 36 questions. SF-36 items cover eight domains: physical functioning, role 7 8 limitations due to physical health problems, body pain, general health, vitality, 9 10 social functioning, role limitations due to emotional problems and mental health. 11 Higher scores indicate higher levels of health. SF-36 will be evaluated at baseline, 12 13 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month follow- 14 15 up). 16 17 2. Chinese Perceived Stress Scale (CPSS) is a self-rated questionnaire that assesses 18 For peer review only 19 perceived stress.25CPSS consists 14 items that are divided into two categories: 20 21 sense of tension and loss of control. Higher scores indicate higher levels of stress. 22 23 CPSS will be evaluated at baseline, 1 month, 3 months (at the end of intervention) 24 25 and 6 months (at the 3-month follow-up). 26 27 28 29 Secondary outcome measures 30 31 1. Body composition measurements will include fat mass, body fat (percentage), fat- 32 33 free mass and lean body mass. These measurements will be taken by bioelectrical 34 35 impedance analysis using an Inbody 770 (Biospace Co) at baseline, 1 month, 3 36 37 months (at the end of intervention) and 6 months (at the 3-month follow-up). http://bmjopen.bmj.com/ 38 39 2. Cardiopulmonary exercise test (CPET) is an objective method being increasingly 40 41 used in a wide spectrum of clinical practice for assessing the functional capacity of 42 43 CHD patients. Indexes include changes in VO2 peak and VAT and VE/ VCO2 slope 44 45 in the cardiopulmonary exercise test (CPET) at the end of the 3-month intervention. on October 5, 2021 by guest. Protected copyright. 46 47 3. Respiratory muscle function will be measured by POWER breath K-5. Indexes 48 49 include changes in S-Index, Peak PIF of inspiratory velocity and power at the end 50 of the 3-month intervention. 51 52 4. Locomotor skills includes handgrip strength, balance and flexibility. Handgrip 53 54 strength, which is used to determine the maximum isometric strength of the hand 55 56 and forearm muscles, will be measured using the handgrip strength dynamometer 57 58 produced by CAMRY (product type EH101). The best result from repeated tests 59 60 14

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1 2 3 4 of each hand will be recorded. The balance will be evaluated by using the time

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 duration until losing balance. We respectively investigated the time duration of 7 8 standing on one foot with eyes closed, standing on one foot with eyes open, 9 ’ 26 10 strengthening Romberg s test . The participants were tested three times to record 11 their time until they lost their balance. Finally, the best of the three was selected. 12 13 Time difference were calculated as the time duration after treatment minus that 14 15 before treatment. Flexibility will be measured by seated forward flexion test. 16 17 Locomotor skills will be evaluated at baseline and at the end of the 3-month 18 For peer review only 19 intervention. 20 21 5. An echocardiogram comprising LVED Vi and LVEF using echocardiography will 22 23 be assessed at baseline and at the end of the 3-month intervention. NYHA 24 25 classification will also be evaluated at baseline and at the end of the 3-month 26 27 intervention. 28 29 6. Heart rate recovery time will be measured. Heart rate recovery time will record 30 31 heart rate 1 to 6 minutes after Tai Chi exercise, power cycling and resistance 32 33 exercise. 34 35 7. A laboratory examination will be performed that includes glycolipid metabolism, 36 37 inflammatory factor level, immunologic function and oxidative stress index. The http://bmjopen.bmj.com/ 38 39 laboratory examination will be evaluated at baseline and at the end of the 3-month 40 41 intervention. 42 43 8. The Berg Balance Scale (BBS) is a widely used clinical test of a person’s static and 44 27 45 dynamic balance abilities , and comprises of a set of 14 simple balance related on October 5, 2021 by guest. Protected copyright. 46 47 tasks, ranging from standing up from a sitting position to standing on one foot. 48 49 Total score ranges from 0 to 56, with 0 to 20 corresponding to a high fall risk, 21 50 to 40 a medium fall risk and 41 to 56 a low fall risk. The Berg Balance Scale will 51 52 be evaluated at baseline and at the end of the 3-month intervention. 53 54 9. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that 55 56 assesses sleep quality and disturbances.28 It contains 19 self-answered questions 57 58 for the subject and 5 peer-answered questions for the bed partner or a roommate (if 59 60 15

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1 2 3 4 one is available). The scores from seven categories are added to calculate the index,

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 ranging from 0 to 21. A score of zero indicates no disturbance in sleep or good 7 8 sleep quality, whereas higher scores indicate poorer sleep quality. The PSQI will 9 10 be evaluated at baseline and at the end of the 3-month intervention. 11 10. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder- 12 13 7(GAD-7) are validated self-answered questionnaires that assess levels of 14 15 depression and anxiety. Higher scores reflect greater levels of anxiety and 16 17 depression. PHQ-9 and GAD-7 will be evaluated at baseline and at the end of the 18 For peer review only 19 3-month intervention. 20 21 11. The Seattle Angina Score (SAQ) will be used to determine the total number of 9 22 23 problems and the 5 aspects of CAD, including the degree of physical activity, the 24 25 stability and frequency of angina, the degree of satisfaction of the treatment, and 26 27 the perception of the disease. The higher the score, the better the quality of life and 28 29 body function. SAQ will be measured at baseline and at the end of the 3-month 30 31 intervention. 32 33 12. A record will be made of any side effects and possible adverse reactions arising 34 35 from the intervention. 36 37 http://bmjopen.bmj.com/ 38 39 Safety measurements 40 41 All study participants are monitored weekly during the study intervention for the 42 43 occurrence of adverse events defined by any undesirable experience. All adverse events 44 45 that occur during the study will be recorded on the Adverse Event Case Report Form on October 5, 2021 by guest. Protected copyright. 46 47 and will be evaluated for relevance to the intervention. All adverse events will also be 48 49 reported to the Human Research Committee promptly in accordance with guidelines. 50 Only patients who are eligible and capable of completing the test will undergo a 51 52 Cardiopulmonary Exercise Test (CPET). For enrolled patients meeting the 53 54 rehabilitation training standards, they will be stratified according to the degree of 55 56 motion risk and appropriate exercise intensity and time will be adjusted based on their 57 58 risk stratification. Before the cardiac rehabilitation exercise, researchers will educate 59 60 16

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1 2 3 4 patients about the CHD rehabilitation exercises, including training contraindications

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 and exercise advisories regarding the respective CER and TCCRP exercises. Moreover, 7 8 the cardiac rehabilitation Center of Chinese PLA General Hospital, Beijing Shuili 9 10 Hospital and Anzhen Community Health Service Center are equipped with a 11 comprehensive set of rescue equipment. A thorough contingency plan and rescue 12 13 procedure for cardiovascular events has also been formulated prior to the 14 15 commencement of the research. Should an adverse event occur during the exercise, the 16 17 researchers will immediately initiate the contingency plan to circumvent the occurrence 18 For peer review only 19 of any fatal outcomes. 20 21 22 23 Data management and monitoring 24 25 Beijing Normal University will be responsible for monitoring research progress, 26 27 managing the data and performing statistical analyses. The research assistants will be 28 29 responsible for checking the integrity of the completed CRF and for timely entry of the 30 31 collected data into the EpiData Manager, a free data management software. The project 32 33 manager will be responsible for initial data cleaning, identifying, coding and converting 34 35 the data into the proper format for analysis. All investigators involved in data 36 37 management and analysis will be blinded to treatment allocation. http://bmjopen.bmj.com/ 38 39 40 41 Statistical analysis 42 43 Continuous variables will be described as mean ± standard deviation (SD) for normal 44 45 distributions or median for non-normal distributions, categorical variables will be on October 5, 2021 by guest. Protected copyright. 46 47 described as frequency. Baseline data mainly describe the clinical characteristic and 48 49 features of the subjects. We also tested the equalization of the two groups of variables. 50 Continuous variables will be described as a two-sample Student’s t-test for normal 51 52 distributions or Wilcoxon test for non-normal distributions. Categorical variables will 53 54 be described as the chi-square test. The group difference between intervention and 55 56 control group at each time point (4 and 12 weeks after intervention or 12-week follow- 57 58 up period) will be analysed using Student’s t-test or Mann-Whitney U-test. A two-way 59 60 17

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1 2 3 4 analysis of variance with repeated measures will be used to determine the effects of

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 time and group on our dependent variables. A Bonferroni-adjusted post hoc analysis 7 8 will be conducted when time-group interaction was detected. The analysis of primary 9 10 or secondary outcomes will be based on an intention to treat (ITT) principle, and 11 participants who either drop out from the study or fail to adhere to the protocol will 12 13 have their last known data carried forward. The missing data will be imputed using a 14 15 multiple imputation method. All data will be analyzed with SPSS 21.0 (IBM, Chicago, 16 17 IL, USA) software packages. Statistical significance is defined as a two-sided P value 18 For peer review only 19 < 0.05. 20 21 22 23 Adherence 24 25 During the 3-month treatment period, participants will be asked to practice strictly 26 27 according to the training program and will not be allowed to take part in any new or 28 29 additional exercise programs. Throughout the 3-month intervention period, the 30 31 researchers will track the number of missed sessions for each participant during the 32 33 intervention period. Participants’ attendance will be monitored during each in-person 34 35 session by staff-completed attendance forms and class sign-in sheets. The percentage 36 37 of compliance will be documented on the case report form. The rate of patient http://bmjopen.bmj.com/ 38 39 compliance = (total planned number of times − number of absence) / total number of 40 41 times × 100%. A compliance rate of 80% or greater will be considered as good, whereas 42 43 a compliance rate of less than 80% is considered as poor. An attendance of less than 20% 44 45 will be considered as a dropout from the study. on October 5, 2021 by guest. Protected copyright. 46 47 48 49 DISCUSSION 50 The development of an ideal and effective cardiac rehabilitation program is still being 51 52 explored and current cardiac rehabilitation mainly consists of contemporary 53 54 conventional exercises. In fact, current cardiac rehabilitation programs have been 55 56 reported to be underdeveloped and limited, reflected by a poor level of involvement 57 58 with less than 30% of patients participating in the existing offerings.29 As such, there is 59 60 18

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1 2 3 4 an unmet need for reforms and the provision of alternative cardiac rehabilitation

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 programs to encourage the growth of cardiac rehabilitation. The exploration of an ideal 7 8 cardiac rehabilitation exercise that is most beneficial for CCS patients should be 9 10 determined. 11 This trial is the first one to compare the safety, feasibility and benefits of TCCRP 12 13 and CER in CCS patients. There are several strengths of our trial: Firstly, the proposed 14 15 research study is unique and the first study about a Bafa Wubu of Tai Chi which is a 16 17 new Tai Chi school. Secondly, TCCRP in this study was specifically designed for 18 For peer review only 19 patients with CCS. Finally, this is the first time for Tai Chi study to develop a 20 21 comparative training system to match the conventional exercise. Our study will supply 22 23 scientific evidence for the promotion of Bafa Wubu of Tai Chi at home and abroad. 24 25 TCCRP has some features which make it more suitable for CCS patients. Firstly, the 26 27 intensity of TCCRP is low, and it is much safer for patients with CCS. Secondly, 28 29 TCCRP is much easier to be learned and possesses a simple structure of movements, a 30 31 reasonable number of postures, and fewer practice environment limitations. Thirdly, 32 33 TCCRP is not limited by location and easy to be carried out. Finally, TCCRP doesn’t 34 35 need money or any equipment. To sum up, compared with conventional exercise 36 37 rehabilitation (CER), TCCRP is more suitable for CCS patients. http://bmjopen.bmj.com/ 38 39 Compared with conventional exercise styles (e.g. aerobic, resistance, and 40 41 extensibility exercise), Tai Chi typically involves a mind–body integration practice that 42 43 combines the coordination of slow movements with mental focus, deep breathing, and 44 30-32 45 relaxation for promoting both physical and mental well-being. Previous studies on October 5, 2021 by guest. Protected copyright. 46 47 have shown that regular Tai Chi exercise is beneficial in improving psychological and 48 49 physiological outcomes among the elderly and various clinical populations (e.g. 50 Parkinson’s disease, diabetes mellitus, hypertension, chronic obstructive pulmonary 51 52 disease (COPD) and psychological illness).33-36 As a typical mind–body exercise which 53 54 incorporates the characteristics of Traditional Chinese Medicine, Tai Chi may be 55 56 considered to be an effective exercise to promote health in a diverse range of 57 58 populations (e.g. healthy population, patients with chronic diseases, youths, middle- 59 60 19

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1 2 3 37 38 4 aged or elderly adults) .

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Compared with other Tai Chi schools, TCCRP has distinct advantages for CCS 7 8 patients. TCCRP utilized Bafa Wubu of Tai Chi, namely, introductory routines to Tai 9 10 Chi characterized by simple structures. Of the many styles of Tai Chi, however, it is 11 hard to further popularize and generalize, due to its numerous movements and 12 13 complexity, especially among patients with CCS. By upholding scientific, standardized 14 15 and simplified principles, the Bafa Wubu of Tai Chi is systematically refined and sorted 16 17 out on the basis of the other forms of Tai Chi, and the two exercise forms of “standing” 18 For peer review only 19 and “marching”, thus forming a set of Tai Chi routines for popularization characterized 20 21 by culture, fitness and simplicity. Compared with the others, Bafa Wubu of Tai Chi is 22 23 safer and much easier to be mastered for patients with CCS. 24 25 It should be acknowledged that this study has several limitations. It is difficult to 26 27 monitor any additional physical activity of participants during the study duration. 28 29 Although all participants will be required to record their daily physical activity or 30 31 exercise information with a pedometer, this is not sufficiently accurate to track their 32 33 daily activity intensity. Furthermore, due to the nature of the exercise interventions (Tai 34 35 Chi versus CER), the blinding of participants is unachievable in this trial. However, 36 37 every effort will be made to ensure that the outcome assessors, data managers and http://bmjopen.bmj.com/ 38 39 statisticians participating in this study will be kept blind of the treatment allocations. 40 41 In conclusion, this study aims to assess the efficacy, safety and acceptability of an 42 43 innovative TCCRP for CCS patients. The finding will be vital to help establish an 44 45 optimal cardiac rehabilitation program for treating CCS patients. on October 5, 2021 by guest. Protected copyright. 46 47 48 49 TRIAL STATUS 50 This trial is currently in the recruitment phase. Estimated completion of the trial is 51 52 expected to be completed by December 2020. 53 54 55 56 Additional files 57 58 Abbreviations 59 60 20

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1 2 3 4 CHD: coronary heart disease; CCS: chronic coronary syndrome; ACS: acute coronary

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 syndromes; TCCRP: Tai Chi cardiac rehabilitation program; TCM: Traditional Chinese 7 8 Medicine; CER: conventional exercise rehabilitation. 9 10 11 Author affiliations 12 13 1College of Physical Education and Sports, Beijing Normal University, Beijing, China 14 15 2 Department of Cardiovascular Medicine, Military General Hospital of Beijing PLA, 16 17 Beijing, China 18 For peer review only 19 3 Anzhen Community Health Service Center, Chaoyang District, Beijing, China 20 21 4 Department of Cardiovascular Medicine, Beijing Shuili Hospital, Beijing, China 22 23 5 College of Wushu, Beijing Sports University, Beijing, China 24 25 26 27 Authors’ contributions 28 29 LSJ, MJ, and YHC conceived and designed the study protocol. The individual 30 31 interviews were conducted by MJ, LH, ZLS, and GAY. ZJW and MJ performed the 32 33 translation and analysed the data. ZJW, YW, CZH, WQY, CMZ, LYM, LYL, GTM, 34 35 LCH, SB and WHW guided and supervised the Tai Chi training. MJ and ZJW 36 37 contributed to writing and reading the manuscript. All authors approved the final http://bmjopen.bmj.com/ 38 39 manuscript. 40 41 42 43 Acknowledgements 44 45 The authors most gratefully thank the physicians and nurses of the Chinese PLA on October 5, 2021 by guest. Protected copyright. 46 47 General Hospital, Beijing Shuili Hospital and Anzhen Community Health Service 48 49 Center, Chaoyang District, Beijing. Thank you for effort working as numbers of Patient 50 Public Involvement group, such as Weiling Guo, Wu Feng, Haibin Wang, Yong Ma 51 52 and Jijun Li. 53 54 55 56 Funding 57 58 This work is financially supported by National Key R&D Program of 59 60 21

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1 2 3 4 China(2018YFC2000600) and Finance Department of the State Administration of

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Traditional Chinese Medicine (GZY-GCS-2018-011) and the Wushu Research Institute 7 8 of the General Administration of Sport of China (WSH2018A004). 9 10 11 Competing interests 12 13 The authors declare that they have no competing interests. 14 15 16 17 Provenance and peer review 18 For peer review only 19 Not commissioned; externally peer reviewed. 20 21 22 23 Data sharing statement 24 25 The data capture system and web servers will be provided by the data management 26 center of Beijing Normal University (http://cas.bnu.edu.cn/cas/login) and the data 27 management belongs to the Wushu and National Traditional Sports Culture Promotion 28 29 Research Center of Beijing Normal University. The results of the review will be 30 disseminated through peer-reviewed publications. 31 32 33 34 Open Access 35 36 This is an open access article distributed in accordance with the Creative Commons http://bmjopen.bmj.com/ 37 Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to 38 39 distribute, remix, adapt, build upon this work non-commercially, and license their 40 41 derivative works on different terms, provided the original work is properly cited and 42 43 the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/ 44 45 © Article author(s) (or their employer(s) unless otherwise stated in the text of the on October 5, 2021 by guest. Protected copyright. 46 47 article) 2019. All rights reserved. No commercial use is permitted unless otherwise 48 49 expressly granted. 50 51 52 53 REFERENCES 54 55 1. Lozano R, Naghavi M, Foreman K, et al., Global and regional mortality from 235 56 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the 57 Global Burden of Disease Study 2010. Lancet 2012; 380:2095-128. 58 2. Mirzaei M, Truswell AS, Taylor R, Leeder SR. Coronary heart disease epidemics: 59 not all the same. Heart 2009; 95:740-6. 60 22

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1 2 3 3. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients 4 with coronary heart disease: systematic review and meta-analysis of randomized 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 controlled trials. Am J Med 2004; 116:682–692. 7 4. Goel K, Lennon RJ, Tibury RT, et al. Impact of cardiac rehabilitation on mortality 8 and cardiovascular events after percutaneous coronary intervention in the 9 community. Circulation 2011;123:2344-52. 10 5. Suaya JA, Stason WB, Ades PA, et al. Cardiac rehabilitation and survival in older 11 coronary patients. J Am Coll Cardiol 2009; 54:25–33 12 6. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients 13 14 with coronary heart disease: systematic review and meta-analysis of randomized 15 controlled trials. Am J Med 2004;116:682-92. 16 7. Smith SCJr, Benjamin EJ, Bonow RO, et al. World Heart Federation and the 17 Preventive Cardiovascular Nurses Association. AHA/ACCF Secondary Prevention 18 and Risk ReductionFor Therapypeer for reviewPatients with Coronary only and other Atherosclerotic 19 Vascular Disease: 2011 update: a guideline from the American Heart Association 20 21 and American College of Cardiology Foundation. Circulation 2011;124:2458– 22 2473. 23 8. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A 24 report of the American College of Cardiology Foundation/American Heart 25 Association Task Force on Practice Guidelines and the Society for Cardiovascular 26 Angiography and Interventions. J Am Coll Cardiol 2011;58: e44–e122. 27 9. Piepoli MF, Hoes AW, Agewall S, etal.2016European Guidelines on 28 29 cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force 30 of the European Society of Cardiology and Other Societies on Cardiovascular 31 Disease Prevention in Clinical Practice (constituted by representatives of 10 32 societies and by invited experts developed with the special contribution of the 33 European Association for Cardiovascular Prevention & Rehabilitation 34 (EACPR).Eur Heart J 2016;37:2315–2381. 35 10. Ritchey MD, Maresh S, McNeely J, et al. Tracking cardiac rehabilitation 36 37 participation and completion among medicare beneficiaries to inform the efforts http://bmjopen.bmj.com/ 38 of a national initiative. Circ Cardiovasc Qual Outcomes 2020. 13(1): e005902. 39 11. Tao T, He T, Wang X, Liu X. Metabolic profiling analysis of patients with 40 coronary heart disease undergoing Xuefu Zhuyu decoction treatment. Front 41 Pharmacol 2019; 10:985. 42 12. Salmoirago-Blotcher E, Wayne PM, Dunsiger S, et al. Tai Chi is a promising 43 44 exercise option for patients with coronary heart disease declining cardiac 45 rehabilitation. J Am Heart Assoc 2017;6(10). on October 5, 2021 by guest. Protected copyright. 46 13. Taylor-Piliae RE, Silva E, Sheremeta SP. Tai Chi as an adjunct physical activity 47 for adults aged 45 years and older enrolled in phase III cardiac rehabilitation. Eur 48 J Cardiovasc Nurs 2012; 11:34-43. 49 14. Sato S, Makita S, Uchida R, Ishihara S, Masuda M. Effect of Tai Chi training on 50 baroreflex sensitivity and heart rate variability in patients with coronary heart 51 52 disease. Int Heart J 2010; 51:238-41. 53 15. Liu T, Chan A W, Liu Y H, Taylor-Piliae RE. Effects of Tai Chi-based cardiac 54 rehabilitation on aerobic endurance, psychosocial well-being and cardiovascular 55 risk reduction among patients with coronary heart disease: A systematic review 56 and meta-analysis. Eur J Cardiovasc Nurs 2018; 17:368-83. 57 16. Jianwei Zhang, Shaojun Lyu, Ji Wang, et al. A comparative study on the 58 therapeutic effect of Taijiquan on patients with type 2 diabetes mellitus of different 59 60 23

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1 2 3 genders . J Beijing Normal University (Nat Sci Ed) 2019;55:545-50 . 4 17. Shaojun Lyu. Bafa Wubu of Tai Chi. Beijing: Beijing Sport University Press. 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 2018;18-20. 7 18. Juhani Knuuti, William Wijns, Antti Saraste, et al. 2019 ESC Guidelines for the 8 diagnosis and management of chronic coronary syndromes: The Task Force for the 9 diagnosis and management of chronic coronary syndromes of the European Society 10 of Cardiology (ESC). Eur Heart J, 2020;41(3):407-477. 11 19. Salvetti XM, Oliveira JA, Servantes DM, et al. How much do the benefits cost? 12 Effects of a home-based training programme on cardiovascular fitness, quality of 13 14 life, programme cost and adherence for patients with coronary disease. Clin 15 Rehabil, 2008. 22(10-11):987-96. 16 20. Zhe Xu. Study on the perioperative nursing practice of TCM auricular compression 17 combined with mindfulness meditation training in patients with colorectal cancer. 18 J Liaoning ForUniv Tradit peer Chin Med,2020.22(02):218-220. review only 19 21. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 20 21 1982;14:377-81 22 22. Fletcher GF, Ades PA, Kligfield P, et al. Exercise standards for testing and training: 23 a scientific statement from the American Heart Association. Circulation 24 2013;128:873-934. 25 23. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from 26 theory to practice. A consensus document of the Heart Failure Association and the 27 European Association for Cardiovascular Prevention and Rehabilitation. Eur J 28 29 Heart Fail 2011;13:347-57. 30 24. Ware JE Jr, Gandek B. Overview of the SF-36 Health Survey and the International 31 Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol 1998;51:903-12. 32 25. Yang T. Psychological stress of urban population in social transition. Chin J 33 Epidemiol 2002;(6):64-6 . 34 26. Yonghao You, Ailing Wen. Human balance assessment method. Chin J Rehabil 35 Med 2014;29(11):1099-1104. 36 37 27. Berg K, Wood-Dauphinee S, Williams JI. The balance scale: reliability assessment http://bmjopen.bmj.com/ 38 for elderly residents and patients with an acute stroke. Scand J Rehab Med 39 1995;27:27-36. 40 28. Buysse DJ, Reynolds III CF, Monk TH, et al. The Pittsburgh Sleep Quality Index: 41 a new instrument for psychiatric practice and research. Psychiatry Res 42 1989;28:193-213. 43 44 29. Gruyter E D, Ford G and Stavreski B. Economic and social impact of increasing 45 uptake of cardiac rehabilitation services – A Cost Benefit Analysis. Heart Lung on October 5, 2021 by guest. Protected copyright. 46 Circ 2016;25:175-83. 47 30. Nery RM, Zanini M, Ferrari JN, et al., Tai Chi Chuan for cardiac rehabilitation in 48 patients with coronary arterial disease. Arq Bras Cardiol 2014;102:588-92. 49 31. Yang YL, Wang YH, Wang, SR, et al. The effect of Tai Chi on cardiorespiratory 50 fitness for coronary disease rehabilitation: A Systematic Review and Meta- 51 52 Analysis. Front Physiol 2018; 8:1091. 53 32. Lan C, Chen SY, Lai JS, et al. The effect of Tai Chi on cardiorespiratory function 54 in patients with coronary artery bypass surgery. Med Sci Sports Exerc 55 1999;31:634-8. 56 33. Chang RY, Koo M, Yu ZR, et al. The effect of Tai Chi exercise on autonomic 57 nervous function of patients with coronary artery disease. J Altern Complement 58 Med 2008; 14:1107-13. 59 60 24

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1 2 3 34. Gao Q, Leung A, Yang Y, et al. Effects of Tai Chi on balance and fall prevention 4 in Parkinson's disease: a randomized controlled trial. Clin Rehabil 2014; 28:748- 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 53. 7 35. Xiao CM, Zhuang YC. Effects of Tai Chi ball on balance and physical function in 8 older adults with type 2 diabetes mellitus. J Am Geriatr Soc 2015;63):176-7. 9 36. Chan AW, Lee A, Lee DT, et al. The sustaining effects of Tai chi Qigong on 10 physiological health for COPD patients: a randomized controlled trial. 11 Complement Ther Med 2013; 21:585-94. 12 37. Chen WW, Sun WY. Tai chi chuan, an alternative form of exercise for health 13 14 promotion and disease prevention for older adults in the community. Int Q 15 Community Health Educ 1996; 16:333-9. 16 38. Guo JB, Chen BL, Lu YM, et al. Tai Chi for improving cardiopulmonary function 17 and quality of life in patients with chronic obstructive pulmonary disease: a 18 systematic reviewFor and peer meta-analysis review. Clin Rehabil only 2016;30:750-64. 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 25

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1 2 3 4 Table 1: Schedule for data collection; outcome measures per visits

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Phase 7 Phase Ι: Phase Π: Phase Ш: Phase Ⅳ: 8 Items Ⅴ: 9 Screening Baseline Month 1 Month 3 10 Month 6 11 12 Inclusion/exclusion criteria √ 13 14 15 Diagnostic index √ 16 17 Signed informed consent √ 18 For peer review only 19 20 Randomization and allocation √ 21 22 Safety index √ √ √ √ 23 24 25 General clinical information √ √ 26 27 28 Primary outcomes √ √ 29 30 Secondary outcomes √ √ 31 32 33 Other indicators √ √ 34 35 Recurrent cardiovascular events √ √ √ 36 37 http://bmjopen.bmj.com/ 38 Adherence √ √ √ 39 40 41 Adverse events √ √ 42 43 Summary at the end of the study √ 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 Figure legend 48 Figure 1: Flow diagram of study design 49 50 SF-36 means the SF-36 Health Survey; CPSS means Chinese Perceived Stress 51 52 Scale; NYHA means New York Heart Association; SAQ means Seattle Angina Scale; 53 PSQI means Pittsburgh Sleep Quality Index; PHQ-9 means Patient Health 54 55 Questionnaire-9; GAD-7 means Generalized Anxiety Disorder-7; BBS means Berg 56 57 Balance Scale. 58 59 60 26

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1 2 3 Figure. 2: Exemplary Bafa Wubu of Tai Chi; the pictures have taken the portrait right; 4

5 the fugleman is the developer of TCCRP. BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 The “Bafa” consisted of eight hand techniques were shown in figure 2. Each figure 8 showed each hand technique, namely “Peng (warding off), Lu (rolling back), Ji 9 10 (pressing), An (pushing), Cai (pulling down), Lie (splitting), Zhou (elbowing) and Kao 11 12 (shouldering)”. 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 27

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1 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 Figure 1: Flow diagram of study design 37 126x119mm (96 x 96 DPI) 38 39 40 41 on October 5, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 29 BMJ Open

1 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 Figure. 2: Exemplary Bafa Wubu of Tai Chi; the pictures have taken the portrait right; the fugleman is the 29 developer of TCCRP. 30 31 149x99mm (96 x 96 DPI) 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on October 5, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from

Article Type: Protocol

Date Submitted by the 16-Mar-2020 Author:

Primary Subject Sports and exercise medicine Heading:

Complementary medicine, Cardiovascular medicine, General practice / Secondary Subject Heading: Family practice, Rehabilitation medicine, Evidence based practice

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1 2 3 4

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1 2 3 4 ID：2019-036061 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Journal：《BMJ Open》 8 9 (1) Article Title： 10 11 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for 12 Chronic Coronary Syndrom Patients: Study Protocol for a Randomized Controlled 13 14 Trial 15 16 17 (2) First-Author 18 For peer review only 19 Jing Ma , Dr 20 Department of Cardiology 21 22 First Medical Center of Chinese People’s Libration Army General Hospital, 23 No. 28, Fuxing road, Haidian district, Beijing 24 25 Zip code: 100853 E-mail: [email protected] 26 27 28 Co- First-Author 29 Jianwei Zhang , PhD 30 31 Beijing Normal University 32 College of Physical Education and Sports 33 No.19 Xinjiekou wai street Haidian district, Beijing 34 35 The People’s Republic of China 36 Zip Code: 100875 37 E-mail: [email protected] http://bmjopen.bmj.com/ 38 39 40 Jing Ma and Jianwei Zhang are joint first authors and contributed equally to this 41 work. 42 43 44

(3) Co-authors on October 5, 2021 by guest. Protected copyright. 45 46 Hua Li 47 48 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 49 50 E-mail:[email protected] 51 52 53 Lianshan Zhao 54 55 Beijing Shuili Hospital, Beijing，China 56 57 E-mail: [email protected] 58 59 Aiying Guo 60 1

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1 2 3 4 Anzhen Community Health Service Center, Chaoyang District，Beijing，China 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 E-mail: [email protected] 7 8 9 Zaihao Chen 10 College of Wushu, Beijing Sports University, Beijing, 100084, China. 11 E-mail: [email protected] 12 13 14 Wen Yuan 15 College of Wushu, Beijing Sports University, Beijing, 100084, China. 16 E-mail: [email protected] 17 18 Tianming Gao For peer review only 19 20 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 21 E-mail:[email protected] 22 23 24 Yameng Li 25 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 26 E-mail: [email protected] 27 28 29 Cuihan Li , Dr 30 College of Wushu, Beijing Sports University, Beijing, 100084, China. 31 E-mail:[email protected] 32 33 34 Hongwei Wang 35 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 36

E-mail: [email protected] http://bmjopen.bmj.com/ 37 38 39 Bo Song 40 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 41 42 E-mail: [email protected] 43 44 Yulong Lu 45 on October 5, 2021 by guest. Protected copyright. 46 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 47 E-mail: [email protected] 48 49 Meize Cui 50 51 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 52 E-mail: [email protected] 53 54 55 Qiuyang Wei 56 College of P.E. and Sports, Beijing Normal University, Beijing, 100875, China. 57 E-mail: [email protected] 58 59 60 2

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1 2 3 4 (4) Corresponding author 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Shaojun Lyu, Ph D 7 Beijing Normal University 8 9 College of Physical Education and Sports 10 No.19 Xinjiekou wai street Haidian district, Beijing 11 The People’s Republic of China 12 Zip Code: 100875 13 14 E-mail: [email protected] 15 16 Tel：+86 13121860699 17 18 Co -CorrespondingFor authorpeer review only 19 20 Hengchan Yin prof 21 22 Beijing Normal University 23 College of Physical Education and Sports 24 No.19 Xinjiekou wai street Haidian district, Beijing 25 The People’s Republic of China 26 27 Zip Code: 100875 28 E-mail: [email protected] 29 30 31 Shaojun Lyu and Hengchan Yin are co-corresponding author. 32 33 34 (5) Keywords 35 36 Coronary heart disease; Complementary medicine; Healthcare; Cardiac rehabilitation; 37 Clinical trials http://bmjopen.bmj.com/ 38 39 (6) Word count: 5112 words 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3

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1 2 3 4 Safety and Effectiveness of a TaiChi-based Cardiac Rehabilitation Program for

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Chronic Coronary Syndrom Patients: Study Protocol for a Randomized 7 8 Controlled Trial 9 ABSTRACT 10 11 Introduction: Preliminary evidence from clinical observations suggests that Tai Chi 12 13 exercise may offer potential benefits for patients with chronic coronary 14 syndrom(CCS). However, the advantages for CCS patients to practice Tai Chi 15 16 exercise as rehabilitation have not been rigorously tested and there is a lack of 17 18 consensus on itsFor benefits. peer This study review aims to develop onlyan innovative Tai Chi Cardiac 19 Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety 20 21 and acceptability of the program. 22 23 24 25 Methods and analysis: We propose to conduct a multicenter randomized‐controlled 26 clinical trial comprising of 150 participants with CCS. The patients will be randomly 27 28 assigned in a 1:1 ratio into two groups. The intervention group will participate in a 29 30 supervised TCCRP held 3 times a week for 3 months. The control group will receive 31 32 supervised conventional exercise rehabilitation (CER) held 3 times a week for 3 33 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 34 35 months after intervention and after an additional 3 months follow-up period. Primary 36 37 outcome measures will include a score of 36-Item Short Form Survey and Chinese http://bmjopen.bmj.com/ 38 Perceived Stress Scale. The secondary outcome measures will include body 39 40 composition, cardiopulmonary exercise test, respiratory muscle function, locomotor 41 42 skills, echocardiogram, New York Heart Association classification, heart rate 43 44 recovery time and laboratory examination. Other measures also include Seattle on October 5, 2021 by guest. Protected copyright. 45 Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, 46 47 Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be 48 49 recorded and analyzed. 50 51 52 Ethics and dissemination: This study conforms to the principles of the Declaration 53 54 of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from 55 56 the Ethics Committee of Chinese PLA General Hospital (approval number: 57 S2019-060-02). Findings from this study will be published and presented at 58 59 conferences for widespread dissemination of the results. 60 4

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1 2 3 4

5 Trial registration number: ClinicalTrials.gov identifier: NCT03936504 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 9 Strengths and limitations of this study: 10 11  The proposed research study is unique and the first study about a Bafa Wubu of 12 13 Tai Chi which is a new Tai Chi school. 14 15  TCCRP in this study was specifically designed for patients with CCS. 16 17  This is the first time for Tai Chi study to develop a comparative training system 18 For peer review only 19 to match the conventional exercise. 20 21  It is difficult to exclude the effect of other physical activity due to difficulty of 22 23 monitoring. 24  The blinding of participants is unachievable in this trial; however, efforts will 25 26 be made to ensure that the data is blinded. 27 28 29 Keywords: Tai Chi, Coronary heart disease, Chronic coronary syndrom, Safety, 30 31 Effectiveness, Randomized controlled trial, Exercise rehabilitation. 32 33 34 35 INTRODUCTION 36 37 Coronary heart disease (CHD) remains the major cause of morbidity and mortality http://bmjopen.bmj.com/ 38 worldwide. CHD responsible for about one in every seven deaths; and, China Heart 39 40 Society is predicted to continue until 2030, accounting for 14% of all deaths globally.1 41 42 2 Despite the use of effective Western medicine treatments, the incidence of CHD 43 44 continues to rise and is associated with a high mortality rate. Cardiac rehabilitation 45 (CR), especially exercise training is proven to significantly alleviate the cardiac on October 5, 2021 by guest. Protected copyright. 46 47 symptoms, preserve the heart function, and improve the clinical outcomes. Therefore 48 3-9 49 cardiac rehabilitation is recommended by many guidelines of different countries. 50 However, latest study demonstrated only 24.4% CR-eligible Medicare beneficiaries 51 52 participated in CR and marked disparities were observed.10 Besides limitation of 53 54 medical resource, poor compliance of patients remains main reason. An effective and 55 56 attractive CR training system is urgently needed. 57 58 These years the integration of Traditional Chinese medicine (TCM) with Western 59 60 5

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1 2 3 4 medicine to treat CHD has made great progress. As an effective complementary

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 11 6 therapy, TCM has been demonstrated to improve the prognosis of CHD patients. Tai 7 8 Chi is an important element of TCM which combines the meridians and collateral 9 10 theory, Yin-Yang theory and Five-element theory. Tai Chi exercise contains three 11 core elements, namely “body”, “breath” and “mind”, as pronounced in Chinese as 12 13 “Xing”, “Qi”, “Yi” respectively. The spirits of Tai Chi are summarized to “building 14 15 the body”, “conveying the breath” and “using the mind”. Previous studies have shown 16 17 that regular Tai Chi exercise was beneficial in improving psychological and 18 For peer review only 19 physiological outcomes among CHD patients.12-15 Study by Professor 20 21 Salmorirago-Blocthcer have showed patients receiving Tai Chi exercise exhibited 22 23 much better compliance than those receiving conventional exercise. 12 24 25 There are many schools in Tai Chi such as the Yang-style, Wu-style, Chen-style, 26 27 Wu-style and Sun-style, wherein each style takes a different approach in terms of the 28 29 movements and forms. Furthermore, as Tai Chi exercise comprises many assorted 30 31 movements that can be also complex to perform, it is difficult to popularize and 32 33 simplify the exercise, especially in elderly patients and patients with chronic diseases. 34 35 Based on prior insights of the Tai Chi movements obtained from our studies and 36 37 other work,16 17 our research team developed an innovative Tai Chi Cardiac http://bmjopen.bmj.com/ 38 39 Rehabilitation Program (TCCRP) specifically for CHD patients. However, as the 40 41 value of TCCRP has not yet to be clinically proven, a clinical trial is required to 42 43 validate the benefits of adopting this exercise for CHD patients. 44 CHD can be categorized as either acute coronary syndrome (ACS) or chronic 45 on October 5, 2021 by guest. Protected copyright. 46 coronary syndrome (CCS) due to pathophysiological features and clinical prognosis 47 48 because it is dynamic process of atherosclerotic plaque accumulation and functional 49 alterations of coronary circulation18. Between the two process, most CHD patients 50 51 stay in the CCS state. Latest studies revealed patients with CCS benefit a lot from 52 53 cardiac rehabilitation programs characterized by life style therapy18. So we chose CCS 54 55 patients as our subjects. This study aims to assess the efficacy, safety, and 56 acceptability of TCCRP for CCS patients. 57 58 59 60 6

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1 2 3 4 The primary hypothesis is that TCCRP (the intervention group) will improve the

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 life quality and reduce the stress when compared against conventional exercise 7 8 rehabilitation (CER, the control group). Secondary objectives are to evaluate the 9 10 effects of the TCCRP on body composition, cardiopulmonary exercise test, 11 respiratory muscle function, locomotor skills, echocardiogram, New York Heart 12 13 Association (NYHA) classification, heart rate recovery time and laboratory 14 15 examination. Other indicators measured will include Seattle Angina Scale (SAQ), 16 17 Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9), 18 For peer review only 19 Generalized Anxiety Disorder-7 (GAD-7), Berg Balance Scale (BBS) and major 20 21 adverse cardiac events. Additional objectives to be explored will include: (1) the 22 23 influence of potential factors on the adherence to the TCCRP; (2) the safety of the 24 25 TCCRP and (3) individual experiences and acceptability following the TCCRP. 26 27 28 29 METHODS/DESIGN 30 31 Study design 32 33 This is a prospective, multicenter, randomized‐controlled clinical trial comparing a 34 35 TCCRP with CER with an allocation ratio of 1:1. The study period lasts for 6 months 36 37 including a 3-month supervised intervention and a 3-month follow-up with the http://bmjopen.bmj.com/ 38 39 primary outcomes measured at baseline, 1 month, 3 months and 6 months. Secondary 40 41 outcomes will be measured at baseline and after a 3-month intervention period. A 42 43 brief flowchart of the entire study is shown in Figure 1 and the schedule of events is 44 45 provided in Table 1. The study protocol is reported according to Standard Protocol on October 5, 2021 by guest. Protected copyright. 46 47 Items: Recommendations for Intervention Trials 2013 (SPIRIT). A SPIRIT Checklist 48 49 is provided in the online supplementary additional file1. The study protocol was 50 submitted to the Ethics Committee of Chinese PLA General Hospital on 26 January 51 52 2019. After 2 revisions, and final version 3 of the protocol was approved on 2 June 53 54 2019(approval number: S2019-060-02). This study is registered on ClinicalTrial.gov 55 56 (NCT03936504). 57 58 59 60 7

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1 2 3 4 Sample size calculation

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Sample size calculation will be based on the co-primary outcomes of the RCT. The 7 8 SF-36 Health Survey (SF-36) and Chinese Perceived Stress Scale (CPSS) are being 9 10 set as the co-primary outcome and used for sample size calculation. Sample size was 11 calculated on the basis of the changes in the SF-36 and CPSS between comparison 12 13 groups with a significance level of 5% and a two-tailed critical region to ensure the 14 15 same effect size with 80% power by G*power V.3.1.9.4 software. The means and 16 17 their SDs (mean ±SD) of the SF-36 and CPSS in the control and intervention group 18 For peer review only 19 were (64.30±13.11, 71.79±16.03)19 and (42.31±8.17, 35.15±6.82)20, respectively, at 20 21 postintervention according to the published literature. Because the sample size 22 23 calculation of CPSS was less than SF-36, the sample size calculation of SF-36 was 24 25 selected. This would require 122 participants, inflated to about 150 to account for the 26 27 loss to follow-up of approximately 20% of participants, with 75 participants being 28 29 assigned to each group. 30 31 32 33 Participants 34 35 Inclusion criteria 36 37 1. Male or non-pregnant women aged from 18 to 80 years; http://bmjopen.bmj.com/ 38 39 2. Patients who met the diagnosis criteria of chronic coronary syndrome 40 18 41 included in ; 42 43 3. NYHA class Ι, Π; 44 45 4. Participants who understood the purpose of the clinical trial and voluntarily on October 5, 2021 by guest. Protected copyright. 46 47 participate with signed informed consent. 48 49 50 Exclusion criteria 51 52 1. Acute myocardial infarction (AMI) within 2 weeks; 53 54 2. Severe aortic stenosis; 55 56 3. Hypertrophic cardiomyopathy; 57 58 4. Severe valvular heart disease; 59 60 8

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1 2 3 4 5. Malignant tachyarrhythmia;

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 6. Poor patient compliance and incompletion of the clinical trial for not 7 8 satisfying the requirements; 9 10 7. Patients with abnormal motor function caused by nervous system 11 deterioration, motor system disease or rheumatic disease; 12 13 8. Those who regularly practice Tai Chi during the previous 3 months. 14 15 16 17 Setting and Recruitment 18 For peer review only 19 This multicenter study will be performed at the Beijing Normal University in China. 20 21 Recruitment and exercise training will occur at the Chinese PLA General Hospital, 22 23 China, Beijing Shuili Hospital, China, and Anzhen Community Health Service 24 25 Center, Beijing Chaoyang District, China. One hundred and fifty participants are to be 26 27 recruited and the recruitment is scheduled to begin in October 2019. Combinations of 28 29 advertising strategies include flyers within the hospital, advertisements in the print, 30 31 online media, a major messaging platform (WeChat), clinics and databases. 32 33 34 35 Randomization, allocation concealment and blinding 36 37 After informed consent is signed, all patients will be randomized into either an http://bmjopen.bmj.com/ 38 39 intervention group receiving a 12-week TCCRP or a control group receiving CER. 40 41 The random allocation sequence will be produced by an independent statistician via 42 43 the PLAN sentences of the statistical software SAS 9.2 in a 1:1 ratio. Next, these 44 45 assignments will be sent to a study staff member, exclusive to the study coordinator or on October 5, 2021 by guest. Protected copyright. 46 47 principal investigator, who will store them into sealed, opaque envelopes with date 48 49 and signature labels placed over the seals of the envelopes. The randomization 50 envelopes will not be opened unless a participant meets eligibility criteria, completes 51 52 the informed consent, and undergoes a baseline assessment. Informed consent will be 53 54 obtained by two blinded research assistants prior to the baseline assessment. Eligible 55 56 participants will receive the information about this trial and have an informed 57 58 discussion with two trained research assistants regarding the information provided. 59 60 9

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1 2 3 4 The study is conducted in 3 different cycles. Each cycle consists of a TCCRP group

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 (intervention group) and CER group (control group). Each resulting group consists of 7 8 25 patients, equating to a 50 patients participating in each cycle, with a total of 150 9 10 patients over the course of the 3 cycles comprising the study. The instructors are 11 randomly assigned to the 3 cycles. 12 13 Given the nature of the intervention, it is impossible to blind the patients or any 14 15 personnel who are directly involved in conducting the programs. However, all 16 17 outcome assessors, laboratory technicians, data managers and statisticians will be kept 18 For peer review only 19 blind of the treatment allocations. 20 21 22 23 Patient and Public Involvement 24 25 We gave priority to patients as far as possible. Patients are the major factor to be 26 consider when designing the trial, subject recruitment and data sharing. Since the very 27 28 beginning of our study, we have constructed a Patient Public Involvement group. 29 30 During the group meeting, Patient Public Involvement group members were informed 31 32 about how the study will be conducted. We always take a lot of time to communicate 33 with patients about how to improve the detail of study to improve their compliance 34 35 and they have given some good advice. For example, the patients suggested us to 36 37 prepare simple booklet to introduce our study during the outpatients visit and by http://bmjopen.bmj.com/ 38 39 internet, also to enlarge the recruitment extent by WeChat and app of our hospital. We 40 planned to disseminate our research to the participants and the public, such as 41 42 publicizing our research in hospital official accounts and various academic lectures. 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 Interventions 47 48 Tai Chi cardiac rehabilitation program (TCCRP) group 49 50 Patients in the intervention group will receive TCCRP conducted by a cardiac 51 52 rehabilitation team consisting of cardiologists, cardiology nurses, Tai Chi coaches and 53 54 research assistants. Procedures and activities of the TCCRP include: (1) Tai Chi 55 56 exercise, (2) evaluation of exercise ability, (3) education covering topics related to the 57 58 exercise, and (4) a series of adherence strategies. 59 60 10

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1 2 3 4 TCCRP pre-phase: a 2-week exercise before the start of exercise 5 1. TCCRP training BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 Six professional coaches with at least 10 years of Tai Chi teaching experience will 8 9 be employed to teach and guide the participants’ training. TCCRP will include (a) 10 11 traditional Tai Chi warm-up exercises, followed by (b) Bafa Wubu of Tai Chi, (c)Tai 12 13 Chi elastic belt exercise and (d) Tai Chi cool-down exercises. 14 15 (a) Tai Chi warm-up exercises (10 minutes) will include traditional breathing 16 17 methods (full-body breathing), weight shifting, arm-swinging etc. These exercises 18 For peer review only 19 will help release tension in the physical body, incorporate mindfulness and imagery 20 21 into movement, increase breathing awareness and promote overall relaxation of the 22 23 body and mind. 24 (b) The core Tai Chi movements (30 minutes) will be adapted from the Bafa Wubu 25 26 of Tai Chi (also known as “eight methods and five footwork”, Fig. 2), which include 27 28 introductory routines to Tai Chi characterized with simple structures and rich 29 30 connotations performed repetitively. Technically speaking, the “Bafa” consists eight 31 32 hand techniques, namely “Peng (warding off), Lu (rolling back), Ji (pressing), An 33 34 (pushing), Cai (pulling down), Lie (splitting), Zhou (elbowing) and Kao 35 36 (shouldering)”; while the “Wubu” consists five footwork, namely “Jin (advancement), 37 http://bmjopen.bmj.com/ 38 Tui (retreat), Gu (shifting left), Pan (shifting right) and Ding (central equilibrium). 39 40 (c) Tai Chi combined with light-weight resistance band exercises(10 minutes) will 41 42 include Tai Chi “Open and Close” movement, Tai Chi Spinning movement and Tai 43 44 Chi Twining movement. 45 on October 5, 2021 by guest. Protected copyright. 46 (d) Tai Chi cool-down exercises (10 minutes) will include various relaxation 47 48 methods, such as regulating breath, regulating body and regulating mind. 49 50 Patients are required to practice the TCCRP until they master it. Mastery will be 51 52 determined by the professional coaches. The mastery of Tai Chi was assessed and 53 54 quantified due to the following 6 factors: the body shape should keep straight and 55 56 upright; the gravity center shift is right; the action moves in an order; moving speed 57 58 has a sense of rhythm; action and movement contains wring and screwing; every set 59 60 11

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1 2 3 4 consumes similar time. We have constructed a testing committee including 10 Tai Chi

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 experts who had discussed together and summerized a scoring criteria concerning the 7 8 above 6 dimensions. Six professional coaches with more than 10 years of Tai Chi 9 10 teaching experiences were trained about the scoring system and then coached the 11 subjects. At the end of learning stage, 3 of coaches were chosen randomly to work as 12 13 the examiner. The professional coaches scored on a percentile basis according to the 14 15 above 6 dimensions. Only the participants who gained an average score higher than 16 17 80 would be certificated to be qualified and move on the to the trial step. 18 For peer review only 19 2. Evaluation of exercise ability (week − 1 to week 0): 20 21 (a) Evaluation is conducted by cardiologists and physiotherapists; 22 23 (b) Evaluation is based on reviewing medical history, cardiopulmonary exercise 24 25 test results and the performance of Tai Chi (heart rate and oxygen consumption 26 27 will be recorded while performing Tai Chi); 28 29 (c) Evaluation results will guide the goal-setting process during consultation; 30 31 3. Education covering topics related to exercise: 32 (a) Basic knowledge of chronic heart disease, 33 34 (b) Basic knowledge of exercise-based cardiac rehabilitation. 35 36 37 http://bmjopen.bmj.com/ 38 TCCRP exercise phase: a 12-week intervention period 39 40 Participants will perform the TCCRP 3 times a week for 12 weeks. Each training 41 42 session is 60 minutes and includes Tai Chi warm-up exercises (10 minutes), Bafa 43 44 Wubu of Tai Chi (30 minutes), Tai Chi combined with light-weight resistance band 45 on October 5, 2021 by guest. Protected copyright. 46 exercises (10 minutes) and Tai Chi cool-down exercises (10 minutes). All participants 47 48 will be encouraged to practice Tai Chi according to an instructional video until the 49 50 end of the 12-week period. 51 52 53 54 Researchers will record the subjects’ heart rate and blood pressure before and after 55 56 training. During the training, the exercise intensity will be assessed by the Borg 57 21 58 Rating of Perceived Exertion Scale (RPE Scale), which is a frequently used 59 60 12

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1 2 3 4 quantitative measure of perceived exertion during exercise.

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 TCCRP follow-up phase: a 12-weeek follow-up period 9 10 After the 12-week TCCRP intervention, there will be a 12-week follow-up period that 11 excludes any active rehabilitation. During the follow-up period, the participants will 12 13 be asked to fill out forms to record the times and durations of their Tai Chi exercise or 14 15 other physical activities and any incidence of a major adverse cardiac event. The 16 17 forms will be returned to the researchers for follow-up each week by email or 18 For peer review only 19 WeChat. 20 21 22 23 CER group (Control group) 24 25 Participants in the control group will receive a CER 3 times a week for 12 weeks. 26 27 Each training session lasts for 60 minutes, including ordinary warm-up exercises (10 28 29 minutes), aerobic activity (30 minutes), resistive exercise (10 minutes) and cool-down 30 31 exercises (10 minutes). Each training session includes: (1) an active warm-up 32 33 including arm-swinging, gentle stretches of the neck, shoulders, spine, arms and legs; 34 35 (2) an aerobic activity comprising primarily cycle ergometer exercise; (3) resistive 36 37 exercise mainly including resistance band exercises; and (4) a cool-down session http://bmjopen.bmj.com/ 38 39 involving active and static stretching exercises with primary body movements. 40 41 The CER program is consistent with the current recommended guidelines of 42 43 moderate intensity exercises (50 to 80% Heart Rate Reserve (HRR); Rated Perceived 44 45 Exertion 11–13) for CHD patients. Our program is individually tailored to each on October 5, 2021 by guest. Protected copyright. 46 47 participant alongside close supervision. The program will be introduced and increased 48 49 in duration and intensity gradually to achieve the target of moderate-intensity 50 exercise. 51 52 53 54 Concomitant treatment 55 56 Participants in both groups will continue routine medications, such as aspirin, 57 58 metoprolol, anti-platelet and anti-coagulant drugs or beta-adrenergic blockers, 59 60 13

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1 2 3 4 according to patients’ respective conditions and will maintain their usual treatment

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 visits throughout the study. All procedures and medication prescriptions will be 7 22 23 8 determined by physicians following the clinical guidelines. The specific date and 9 10 reasons of any medical therapy changes will be recorded in the case report form 11 (CRF). 12 13 14 15 Outcome measures 16 17 All outcome measures will be collected by 3 research assistants at 2 weeks (baseline), 18 For peer review only 19 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month 20 21 follow-up). Demographic information collected will include age, gender, ethnicity, 22 23 marital status, education level, accommodation type and postal address. Clinical 24 25 information will also be obtained from the patients’ clinical records by a member of 26 27 their hospital research team. All data collected from the assistants and therapists will 28 29 be stored in a dedicated computer for the study and will be kept in a secure and 30 31 lock-protected location. 32 33 34 35 Primary outcome measures 36 37 1. The SF-36 Health Survey (SF-36) is a multi-purpose, short-form health survey http://bmjopen.bmj.com/ 38 39 with only 36 questions.24 SF-36 items cover eight domains: physical functioning, 40 41 role limitations due to physical health problems, body pain, general health, 42 43 vitality, social functioning, role limitations due to emotional problems and mental 44 45 health. Higher scores indicate higher levels of health. SF-36 will be evaluated at on October 5, 2021 by guest. Protected copyright. 46 47 baseline, 1 month, 3 months (at the end of intervention) and 6 months (at the 48 49 3-month follow-up). 50 2. Chinese Perceived Stress Scale (CPSS) is a self-rated questionnaire that assesses 51 52 perceived stress.25CPSS consists 14 items that are divided into two categories: 53 54 sense of tension and loss of control. Higher scores indicate higher levels of stress. 55 56 CPSS will be evaluated at baseline, 1 month, 3 months (at the end of 57 58 intervention) and 6 months (at the 3-month follow-up). 59 60 14

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1 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Secondary outcome measures 7 8 1. Body composition measurements will include fat mass, body fat (percentage), 9 10 fat-free mass and lean body mass. These measurements will be taken by 11 bioelectrical impedance analysis using an Inbody 770 (Biospace Co) at baseline, 12 13 1 month, 3 months (at the end of intervention) and 6 months (at the 3-month 14 15 follow-up). 16 17 2. Cardiopulmonary exercise test (CPET) is an objective method being increasingly 18 For peer review only 19 used in a wide spectrum of clinical practice for assessing the functional capacity 20 21 of CHD patients. Indexes include changes in VO2 peak and VAT and VE/ VCO2 22 23 slope in the cardiopulmonary exercise test (CPET) at the end of the 3-month 24 25 intervention. 26 27 3. Respiratory muscle function will be measured by POWER breath K-5. Indexes 28 29 include changes in S-Index, Peak PIF of inspiratory velocity and power at the end 30 31 of the 3-month intervention. 32 33 4. Locomotor skills includes handgrip strength, balance and flexibility. Handgrip 34 35 strength, which is used to determine the maximum isometric strength of the hand 36 37 and forearm muscles, will be measured using the handgrip strength dynamometer http://bmjopen.bmj.com/ 38 39 produced by CAMRY (product type EH101). The best result from repeated tests 40 41 of each hand will be recorded. The balance will be evaluated by using the time 42 43 duration until losing balance. We respectively investigated the time duration of 44 45 standing on one foot with eyes closed, standing on one foot with eyes open, on October 5, 2021 by guest. Protected copyright. 46 ’ 26 47 strengthening Romberg s test . The participants were tested three times to 48 49 record their time until they lost their balance. Finally, the best of the three was 50 selected. Time difference were calculated as the time duration after treatment 51 52 minus that before treatment. Flexibility will be measured by seated forward 53 54 flexion test. Locomotor skills will be evaluated at baseline and at the end of the 55 56 3-month intervention. 57 58 5. An echocardiogram comprising LVED Vi and LVEF using echocardiography 59 60 15

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1 2 3 4 will be assessed at baseline and at the end of the 3-month intervention. NYHA

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 classification will also be evaluated at baseline and at the end of the 3-month 7 8 intervention. 9 10 6. Heart rate recovery time will be measured. Heart rate recovery time will record 11 heart rate 1 to 6 minutes after Tai Chi exercise, power cycling and resistance 12 13 exercise. 14 15 7. A laboratory examination will be performed that includes glycolipid metabolism, 16 17 inflammatory factor level, immunologic function and oxidative stress index. The 18 For peer review only 19 laboratory examination will be evaluated at baseline and at the end of the 20 21 3-month intervention. 22 23 8. The Berg Balance Scale (BBS) is a widely used clinical test of a person’s static 24 25 and dynamic balance abilities27, and comprises of a set of 14 simple balance 26 27 related tasks, ranging from standing up from a sitting position to standing on one 28 29 foot. Total score ranges from 0 to 56, with 0 to 20 corresponding to a high fall 30 31 risk, 21 to 40 a medium fall risk and 41 to 56 a low fall risk. The Berg Balance 32 33 Scale will be evaluated at baseline and at the end of the 3-month intervention. 34 35 9. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that 36 37 assesses sleep quality and disturbances.28 It contains 19 self-answered questions http://bmjopen.bmj.com/ 38 39 for the subject and 5 peer-answered questions for the bed partner or a roommate 40 41 (if one is available). The scores from seven categories are added to calculate the 42 43 index, ranging from 0 to 21. A score of zero indicates no disturbance in sleep or 44 45 good sleep quality, whereas higher scores indicate poorer sleep quality. The PSQI on October 5, 2021 by guest. Protected copyright. 46 47 will be evaluated at baseline and at the end of the 3-month intervention. 48 49 10. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety 50 Disorder-7(GAD-7) are validated self-answered questionnaires that assess levels 51 52 of depression and anxiety. Higher scores reflect greater levels of anxiety and 53 54 depression. PHQ-9 and GAD-7 will be evaluated at baseline and at the end of the 55 56 3-month intervention. 57 58 11. The Seattle Angina Score (SAQ) will be used to determine the total number of 9 59 60 16

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1 2 3 4 problems and the 5 aspects of CAD, including the degree of physical activity, the

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 stability and frequency of angina, the degree of satisfaction of the treatment, and 7 8 the perception of the disease. The higher the score, the better the quality of life 9 10 and body function. SAQ will be measured at baseline and at the end of the 11 3-month intervention. 12 13 12. A record will be made of any side effects and possible adverse reactions arising 14 15 from the intervention. 16 17 18 For peer review only 19 Safety measurements 20 21 All study participants are monitored weekly during the study intervention for the 22 23 occurrence of adverse events defined by any undesirable experience. All adverse 24 25 events that occur during the study will be recorded on the Adverse Event Case Report 26 27 Form and will be evaluated for relevance to the intervention. All adverse events will 28 29 also be reported to the Human Research Committee promptly in accordance with 30 31 guidelines. 32 33 Only patients who are eligible and capable of completing the test will undergo a 34 35 Cardiopulmonary Exercise Test (CPET). For enrolled patients meeting the 36 37 rehabilitation training standards, they will be stratified according to the degree of http://bmjopen.bmj.com/ 38 39 motion risk and appropriate exercise intensity and time will be adjusted based on their 40 41 risk stratification. Before the cardiac rehabilitation exercise, researchers will educate 42 43 patients about the CHD rehabilitation exercises, including training contraindications 44 45 and exercise advisories regarding the respective CER and TCCRP exercises. on October 5, 2021 by guest. Protected copyright. 46 47 Moreover, the cardiac rehabilitation Center of Chinese PLA General Hospital, Beijing 48 49 Shuili Hospital and Anzhen Community Health Service Center are equipped with a 50 comprehensive set of rescue equipment. A thorough contingency plan and rescue 51 52 procedure for cardiovascular events has also been formulated prior to the 53 54 commencement of the research. Should an adverse event occur during the exercise, 55 56 the researchers will immediately initiate the contingency plan to circumvent the 57 58 occurrence of any fatal outcomes. 59 60 17

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5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Data management and monitoring 7 8 Beijing Normal University will be responsible for managing the data and performing 9 10 statistical analyses. The research assistants will be responsible for checking the 11 integrity of the completed CRF and for timely entry of the collected data into the 12 13 EpiData Manager, a free data management software. The project manager will be 14 15 responsible for initial data cleaning, identifying, coding and converting the data into 16 17 the proper format for analysis. All investigators involved in data management and 18 For peer review only 19 analysis will be blinded to treatment allocation. Regular monitoring by the sponsor of 20 21 China National Center for Biotechnology Development will be performed according 22 23 to ICH GCP. China National Center for Biotechnology Development will be 24 25 responsible for monitoring the research progress and meet every three months. It will 26 27 oversee all aspects of the trial delivery including protocol amendments, recruitment of 28 29 participants, monitoring intervention fidelity, management of timelines and 30 31 milestones, publication and dissemination plans. Each amendment of the protocol 32 33 conforms to the GCP principles and is submitted to the Ethics Committee for 34 35 approval. 36 37 Statistical analysis http://bmjopen.bmj.com/ 38 39 Continuous variables will be described as mean ± standard deviation (SD) for normal 40 41 distributions or median for non-normal distributions, categorical variables will be 42 43 described as frequency. Baseline data mainly describe the clinical characteristic and 44 45 features of the subjects. We also tested the equalization of the two groups of variables. on October 5, 2021 by guest. Protected copyright. 46 47 Continuous variables will be described as a two-sample Student’s t-test for normal 48 49 distributions or Wilcoxon test for non-normal distributions. Categorical variables will 50 be described as the chi-square test. The group difference between intervention and 51 52 control group at each time point (4 and 12 weeks after intervention or 12-week 53 54 follow-up period) will be analysed using Student’s t-test or Mann-Whitney U-test. A 55 56 two-way analysis of variance with repeated measures will be used to determine the 57 58 effects of time and group on our dependent variables. A Bonferroni-adjusted post hoc 59 60 18

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1 2 3 4 analysis will be conducted when time-group interaction was detected. The analysis

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 of primary or secondary outcomes will be based on an intention to treat (ITT) 7 8 principle, and participants who either drop out from the study or fail to adhere to the 9 10 protocol will have their last known data carried forward. The missing data will be 11 imputed using a multiple imputation method. All data will be analyzed with SPSS 12 13 21.0 (IBM, Chicago, IL, USA) software packages. Statistical significance is defined 14 15 as a two-sided P value < 0.05. 16 17 18 For peer review only 19 Adherence 20 21 To motivate participants’ adherence, the research group will use several strategies 22 23 (e.g. ancillary and post-trial care) to ensure the participants stays for the entire study 24 25 period. (1) The participants will receive 36 cardiac rehabilitation treatments free of 26 27 charge, for a total price of about 10,000 RMB; (2) the participants will be entitled 28 29 specialist outpatient priority plus; (3) participants will be given three free face-to-face 30 31 health education lectures by specialists; In addition, participant who complete the 32 33 protocol successfully will be rewarded with Wushu training clothing no matter which 34 35 group they belongs to. During the 3-month treatment period, participants will be 36 37 asked to practice strictly according to the training program and will not be allowed to http://bmjopen.bmj.com/ 38 39 take part in any new or additional exercise programs. Throughout the 3-month 40 41 intervention period, the researchers will track the number of missed sessions for each 42 43 participant during the intervention period. Participants’ attendance will be monitored 44 45 during each in-person session by staff-completed attendance forms and class sign-in on October 5, 2021 by guest. Protected copyright. 46 47 sheets. The percentage of compliance will be documented on the case report form. 48 49 The rate of patient compliance = (total planned number of times − number of absence) 50 / total number of times × 100%. A compliance rate of 80% or greater will be 51 52 considered as good, whereas a compliance rate of less than 80% is considered as poor. 53 54 An attendance of less than 20% will be considered as a dropout from the study. 55 56 57 58 Ethics and dissemination 59 60 19

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1 2 3 4 This study conforms to the principles of the Declaration of Helsinki and relevant

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 ethical guidelines. Ethical approval and informed consent form have been obtained 7 8 from the Ethics Committee of Chinese PLA General Hospital (approval number: 9 10 S2019-060-02). The study background and main objective as well as potential 11 benefits and risks will be fully explained to the participants and their families. 12 13 Findings from this study will be published and presented at conferences for 14 15 widespread dissemination of the results. 16 17 18 For peer review only 19 DISCUSSION 20 21 The development of an ideal and effective cardiac rehabilitation program is still being 22 23 explored and current cardiac rehabilitation mainly consists of contemporary 24 25 conventional exercises. In fact, current cardiac rehabilitation programs have been 26 27 reported to be underdeveloped and limited, reflected by a poor level of involvement 28 29 with less than 30% of patients participating in the existing offerings.29 As such, there 30 31 is an unmet need for reforms and the provision of alternative cardiac rehabilitation 32 33 programs to encourage the growth of cardiac rehabilitation. The exploration of an 34 35 ideal cardiac rehabilitation exercise that is most beneficial for CCS patients should be 36 37 determined. http://bmjopen.bmj.com/ 38 39 This trial is the first one to compare the safety, feasibility and benefits of TCCRP 40 41 and CER in CCS patients. There are several strengths of our trial: Firstly, the 42 43 proposed research study is unique and the first study about a Bafa Wubu of Tai Chi 44 45 which is a new Tai Chi school. Secondly, TCCRP in this study was specifically on October 5, 2021 by guest. Protected copyright. 46 47 designed for patients with CCS. Finally, this is the first time for Tai Chi study to 48 49 develop a comparative training system to match the conventional exercise. Our study 50 will supply scientific evidence for the promotion of Bafa Wubu of Tai Chi at home 51 52 and abroad. 53 54 TCCRP has some features which make it more suitable for CCS patients. Firstly, 55 56 the intensity of TCCRP is low, and it is much safer for patients with CCS. Secondly, 57 58 TCCRP is much easier to be learned and possesses a simple structure of movements, a 59 60 20

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1 2 3 4 reasonable number of postures, and fewer practice environment limitations. Thirdly,

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 TCCRP is not limited by location and easy to be carried out. Finally, TCCRP doesn’t 7 8 need money or any equipment. To sum up, compared with conventional exercise 9 10 rehabilitation (CER), TCCRP is more suitable for CCS patients. 11 Compared with conventional exercise styles (e.g. aerobic, resistance, and 12 13 extensibility exercise), Tai Chi typically involves a mind–body integration practice 14 15 that combines the coordination of slow movements with mental focus, deep breathing, 16 17 and relaxation for promoting both physical and mental well-being.30-32 Previous 18 For peer review only 19 studies have shown that regular Tai Chi exercise is beneficial in improving 20 21 psychological and physiological outcomes among the elderly and various clinical 22 23 populations (e.g. Parkinson’s disease, diabetes mellitus, hypertension, chronic 24 25 obstructive pulmonary disease (COPD) and psychological illness).33-36 As a typical 26 27 mind–body exercise which incorporates the characteristics of Traditional Chinese 28 29 Medicine, Tai Chi may be considered to be an effective exercise to promote health in 30 31 a diverse range of populations (e.g. healthy population, patients with chronic diseases, 32 33 youths, middle-aged or elderly adults) .37 38 34 35 Compared with other Tai Chi schools, TCCRP has distinct advantages for CCS 36 37 patients. TCCRP utilized Bafa Wubu of Tai Chi, namely, introductory routines to Tai http://bmjopen.bmj.com/ 38 39 Chi characterized by simple structures. Of the many styles of Tai Chi, however, it is 40 41 hard to further popularize and generalize, due to its numerous movements and 42 43 complexity, especially among patients with CCS. By upholding scientific, 44 45 standardized and simplified principles, the Bafa Wubu of Tai Chi is systematically on October 5, 2021 by guest. Protected copyright. 46 47 refined and sorted out on the basis of the other forms of Tai Chi, and the two exercise 48 49 forms of “standing” and “marching”, thus forming a set of Tai Chi routines for 50 popularization characterized by culture, fitness and simplicity. Compared with the 51 52 others, Bafa Wubu of Tai Chi is safer and much easier to be mastered for patients 53 54 with CCS. 55 56 It should be acknowledged that this study has several limitations. It is difficult to 57 58 monitor any additional physical activity of participants during the study duration. 59 60 21

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1 2 3 4 Although all participants will be required to record their daily physical activity or

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 exercise information with a pedometer, this is not sufficiently accurate to track their 7 8 daily activity intensity. Furthermore, due to the nature of the exercise interventions 9 10 (Tai Chi versus CER), the blinding of participants is unachievable in this trial. 11 However, every effort will be made to ensure that the outcome assessors, data 12 13 managers and statisticians participating in this study will be kept blind of the 14 15 treatment allocations. 16 17 In conclusion, this study aims to assess the efficacy, safety and acceptability of an 18 For peer review only 19 innovative TCCRP for CCS patients. The finding will be vital to help establish an 20 21 optimal cardiac rehabilitation program for treating CCS patients. 22 23 24 25 TRIAL STATUS 26 27 This trial is currently in the recruitment phase. Estimated completion of the trial is 28 29 expected to be completed by December 2020. 30 31 32 33 Additional files 34 35 Abbreviations 36 37 CHD: coronary heart disease; CCS: chronic coronary syndrome; ACS: acute coronary http://bmjopen.bmj.com/ 38 39 syndromes; TCCRP: Tai Chi cardiac rehabilitation program; TCM: Traditional 40 41 Chinese Medicine; CER: conventional exercise rehabilitation. 42 43 44 45 Author affiliations on October 5, 2021 by guest. Protected copyright. 46 47 1College of Physical Education and Sports, Beijing Normal University, Beijing, 48 49 China 50 2 Department of Cardiovascular Medicine, Military General Hospital of Beijing PLA, 51 52 Beijing, China 53 54 3 Anzhen Community Health Service Center, Chaoyang District, Beijing, China 55 56 4 Department of Cardiovascular Medicine, Beijing Shuili Hospital, Beijing, China 57 58 5 College of Wushu, Beijing Sports University, Beijing, China 59 60 22

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1 2 3 4

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Authors’ contributions 7 8 LSJ, MJ, and YHC conceived and designed the study protocol. The individual 9 10 interviews were conducted by LSJ, MJ, LH, ZLS, and GAY. ZJW and MJ performed 11 the translation and analysed the data. LSJ, ZJW, YW, CZH, WQY, CMZ, LYM, 12 13 LYL, GTM, LCH, SB and WHW guided and supervised the Tai Chi training. ZJW 14 15 and MJ contributed to writing and reading the manuscript. All authors approved the 16 17 final manuscript. 18 For peer review only 19 20 21 Acknowledgements 22 23 The authors most gratefully thank the physicians and nurses of the Chinese PLA 24 25 General Hospital, Beijing Shuili Hospital and Anzhen Community Health Service 26 27 Center, Chaoyang District, Beijing. Thank you for effort working as numbers of 28 29 Patient Public Involvement group, such as Weiling Guo, Wu Feng, Haibin Wang, 30 31 Yong Ma and Jijun Li. 32 33 34 35 Funding 36 37 This work is financially supported by National Key R&D Program of http://bmjopen.bmj.com/ 38 39 China(2018YFC2000600) and Finance Department of the State Administration of 40 41 Traditional Chinese Medicine (GZY-GCS-2018-011) and the Wushu Research 42 43 Institute of the General Administration of Sport of China (WSH2018A004). 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 Competing interests 48 49 None declared. 50 51 52 Patient consent for publication 53 54 Not required. 55 56 57 58 Provenance and peer review 59 60 23

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1 2 3 4 Not commissioned; externally peer reviewed.

5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 Data sharing statement 9 10 The data capture system and web servers will be provided by the data management 11 center of Beijing Normal University (http://cas.bnu.edu.cn/cas/login) and the data 12 13 management belongs to the Wushu and National Traditional Sports Culture 14 15 Promotion Research Center of Beijing Normal University. The results of the review 16 17 will be disseminated through peer-reviewed publications. 18 For peer review only 19 20 21 Open Access 22 23 This is an open access article distributed in accordance with the Creative Commons 24 25 Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to 26 27 distribute, remix, adapt, build upon this work non-commercially, and license their 28 29 derivative works on different terms, provided the original work is properly cited and 30 31 the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/ 32 33 © Article author(s) (or their employer(s) unless otherwise stated in the text of the 34 35 article) 2019. All rights reserved. No commercial use is permitted unless otherwise 36 37 expressly granted. http://bmjopen.bmj.com/ 38 39 40 41 REFERENCES 42 1. Lozano R, Naghavi M, Foreman K, et al., Global and regional mortality from 235 43 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the 44 45 Global Burden of Disease Study 2010. Lancet 2012; 380:2095-128. on October 5, 2021 by guest. Protected copyright. 46 2. Mirzaei M, Truswell AS, Taylor R, Leeder SR. Coronary heart disease 47 epidemics: not all the same. Heart 2009; 95:740-6. 48 3. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients 49 with coronary heart disease: systematic review and meta-analysis of randomized 50 controlled trials. Am J Med 2004; 116:682–692. 51 4. Goel K, Lennon RJ, Tibury RT, et al. Impact of cardiac rehabilitation on 52 53 mortality and cardiovascular events after percutaneous coronary intervention in 54 the community. Circulation 2011;123:2344-52. 55 5. Suaya JA, Stason WB, Ades PA, et al. Cardiac rehabilitation and survival in older 56 coronary patients. J Am Coll Cardiol 2009; 54:25–33 57 6. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients 58 with coronary heart disease: systematic review and meta-analysis of randomized 59 60 controlled trials. Am J Med 2004;116:682-92. 24

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1 2 3 7. Smith SCJr, Benjamin EJ, Bonow RO, et al. World Heart Federation and the 4 Preventive Cardiovascular Nurses Association. AHA/ACCF Secondary 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 Prevention and Risk Reduction Therapy for Patients with Coronary and other 7 Atherosclerotic Vascular Disease: 2011 update: a guideline from the American 8 Heart Association and American College of Cardiology Foundation. Circulation 9 2011;124:2458–2473. 10 8. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A 11 report of the American College of Cardiology Foundation/American Heart 12 Association Task Force on Practice Guidelines and the Society for 13 14 Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011;58: e44– 15 e122. 16 9. Piepoli MF, Hoes AW, Agewall S, etal.2016European Guidelines on 17 cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force 18 of the EuropeanFor Society peer of Cardiology review and Other only Societies on Cardiovascular 19 Disease Prevention in Clinical Practice (constituted by representatives of 10 20 21 societies and by invited experts developed with the special contribution of the 22 European Association for Cardiovascular Prevention & Rehabilitation 23 (EACPR).Eur Heart J 2016;37:2315–2381. 24 10. Ritchey MD, Maresh S, McNeely J, et al. Tracking cardiac rehabilitation 25 participation and completion among medicare beneficiaries to inform the efforts 26 of a national initiative. Circ Cardiovasc Qual Outcomes 2020. 13(1): e005902. 27 11. Tao T, He T, Wang X, Liu X. Metabolic profiling analysis of patients with 28 29 coronary heart disease undergoing Xuefu Zhuyu decoction treatment. Front 30 Pharmacol 2019; 10:985. 31 12. Salmoirago-Blotcher E, Wayne PM, Dunsiger S, et al. Tai Chi is a promising 32 exercise option for patients with coronary heart disease declining cardiac 33 rehabilitation. J Am Heart Assoc 2017;6(10). 34 13. Taylor-Piliae RE, Silva E, Sheremeta SP. Tai Chi as an adjunct physical activity 35 for adults aged 45 years and older enrolled in phase III cardiac rehabilitation. Eur 36 37 J Cardiovasc Nurs 2012; 11:34-43. http://bmjopen.bmj.com/ 38 14. Sato S, Makita S, Uchida R, Ishihara S, Masuda M. Effect of Tai Chi training on 39 baroreflex sensitivity and heart rate variability in patients with coronary heart 40 disease. Int Heart J 2010; 51:238-41. 41 15. Liu T, Chan A W, Liu Y H, Taylor-Piliae RE. Effects of Tai Chi-based cardiac 42 rehabilitation on aerobic endurance, psychosocial well-being and cardiovascular 43 44 risk reduction among patients with coronary heart disease: A systematic review 45 and meta-analysis. Eur J Cardiovasc Nurs 2018; 17:368-83. on October 5, 2021 by guest. Protected copyright. 46 16. Jianwei Zhang, Shaojun Lyu, Ji Wang, et al. A comparative study on the 47 therapeutic effect of Taijiquan on patients with type 2 diabetes mellitus of 48 different genders . J Beijing Normal University (Nat Sci Ed) 2019;55:545-50 . 49 17. Shaojun Lyu. Bafa Wubu of Tai Chi. Beijing: Beijing Sport University Press. 50 2018;18-20. 51 52 18. Juhani Knuuti, William Wijns, Antti Saraste, et al. 2019 ESC Guidelines for the 53 diagnosis and management of chronic coronary syndromes: The Task Force for 54 the diagnosis and management of chronic coronary syndromes of the European 55 Society of Cardiology (ESC). Eur Heart J, 2020;41(3):407-477. 56 19. Salvetti XM, Oliveira JA, Servantes DM, et al. How much do the benefits cost? 57 Effects of a home-based training programme on cardiovascular fitness, quality of 58 life, programme cost and adherence for patients with coronary disease. Clin 59 60 25

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1 2 3 Rehabil, 2008. 22(10-11):987-96. 4 20. Zhe Xu. Study on the perioperative nursing practice of TCM auricular 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 compression combined with mindfulness meditation training in patients with 7 colorectal cancer. J Liaoning Univ Tradit Chin Med,2020.22(02):218-220. 8 21. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 9 1982;14:377-81 10 22. Fletcher GF, Ades PA, Kligfield P, et al. Exercise standards for testing and 11 training: a scientific statement from the American Heart Association. Circulation 12 2013;128:873-934. 13 14 23. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from 15 theory to practice. A consensus document of the Heart Failure Association and 16 the European Association for Cardiovascular Prevention and Rehabilitation. Eur 17 J Heart Fail 2011;13:347-57. 18 24. Ware JE For Jr, Gandek peer B. Overview review of the SF-36 only Health Survey and the 19 International Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol 20 21 1998;51:903-12. 22 25. Yang T. Psychological stress of urban population in social transition. Chin J 23 Epidemiol 2002;(6):64-6 . 24 26. Yonghao You, Ailing Wen. Human balance assessment method. Chin J Rehabil 25 Med 2014;29(11):1099-1104. 26 27. Berg K, Wood-Dauphinee S, Williams JI. The balance scale: reliability 27 assessment for elderly residents and patients with an acute stroke. Scand J Rehab 28 29 Med 1995;27:27-36. 30 28. Buysse DJ, Reynolds III CF, Monk TH, et al. The Pittsburgh Sleep Quality 31 Index: a new instrument for psychiatric practice and research. Psychiatry Res 32 1989;28:193-213. 33 29. Gruyter E D, Ford G and Stavreski B. Economic and social impact of increasing 34 uptake of cardiac rehabilitation services – A Cost Benefit Analysis. Heart Lung 35 Circ 2016;25:175-83. 36 37 30. Nery RM, Zanini M, Ferrari JN, et al., Tai Chi Chuan for cardiac rehabilitation in http://bmjopen.bmj.com/ 38 patients with coronary arterial disease. Arq Bras Cardiol 2014;102:588-92. 39 31. Yang YL, Wang YH, Wang, SR, et al. The effect of Tai Chi on cardiorespiratory 40 fitness for coronary disease rehabilitation: A Systematic Review and 41 Meta-Analysis. Front Physiol 2018; 8:1091. 42 32. Lan C, Chen SY, Lai JS, et al. The effect of Tai Chi on cardiorespiratory function 43 44 in patients with coronary artery bypass surgery. Med Sci Sports Exerc 45 1999;31:634-8. on October 5, 2021 by guest. Protected copyright. 46 33. Chang RY, Koo M, Yu ZR, et al. The effect of Tai Chi exercise on autonomic 47 nervous function of patients with coronary artery disease. J Altern Complement 48 Med 2008; 14:1107-13. 49 34. Gao Q, Leung A, Yang Y, et al. Effects of Tai Chi on balance and fall prevention 50 in Parkinson's disease: a randomized controlled trial. Clin Rehabil 2014; 51 52 28:748-53. 53 35. Xiao CM, Zhuang YC. Effects of Tai Chi ball on balance and physical function 54 in older adults with type 2 diabetes mellitus. J Am Geriatr Soc 2015;63):176-7. 55 36. Chan AW, Lee A, Lee DT, et al. The sustaining effects of Tai chi Qigong on 56 physiological health for COPD patients: a randomized controlled trial. 57 Complement Ther Med 2013; 21:585-94. 58 37. Chen WW, Sun WY. Tai chi chuan, an alternative form of exercise for health 59 60 26

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1 2 3 promotion and disease prevention for older adults in the community. Int Q 4 Community Health Educ 1996; 16:333-9. 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 38. Guo JB, Chen BL, Lu YM, et al. Tai Chi for improving cardiopulmonary function 7 and quality of life in patients with chronic obstructive pulmonary disease: a 8 systematic review and meta-analysis. Clin Rehabil 2016;30:750-64. 9 10 11 12 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 27

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1 2 3 4 Table 1: Schedule for data collection; outcome measures per visits

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1 2 3 Figure. 2: Exemplary Bafa Wubu of Tai Chi; the pictures have taken the portrait right; 4

5 the fugleman is the developer of TCCRP. BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 The “Bafa” consisted of eight hand techniques were shown in figure 2. Each figure 8 showed each hand technique, namely “Peng (warding off), Lu (rolling back), Ji 9 10 (pressing), An (pushing), Cai (pulling down), Lie (splitting), Zhou (elbowing) and 11 12 Kao (shouldering)”. 13 14 15 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 29

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1 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 Figure 1: Flow diagram of study design 37 126x119mm (96 x 96 DPI) 38 39 40 41 on October 5, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 36 BMJ Open

1 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 Figure. 2: Exemplary Bafa Wubu of Tai Chi; the pictures have taken the portrait right; the fugleman is the 28 developer of TCCRP. 29 219x136mm (96 x 96 DPI) 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on October 5, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 36

1 2 3 4 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and 9 related documents* 10 11 Section/item Item Description 12 No 13 14 Administrative information 15 16 Title（P1） 1 Descriptive title identifying the study design, population, interventions, 17 and, if applicable, trial acronym 18 For peer review only 19 Trial registration 2a Trial identifier and registry name. If not yet registered, name of 20 （P7） intended registry 21 22 2b All items from the World Health Organization Trial Registration Data 23 24 Set 25 26 Protocol 3 Date and version identifier 27 version(P7) 28 29 Funding（P23） 4 Sources and types of financial, material, and other support 30 31 Roles and 5a Names, affiliations, and roles of protocol contributors 32 responsibilities 5b Name and contact information for the trial sponsor 33 （P22） 34 35 5c Role of study sponsor and funders, if any, in study design; collection, 36

management, analysis, and interpretation of data; writing of the report; http://bmjopen.bmj.com/ 37 38 and the decision to submit the report for publication, including whether 39 they will have ultimate authority over any of these activities 40 41 5d Composition, roles, and responsibilities of the coordinating centre, 42 steering committee, endpoint adjudication committee, data 43 management team, and other individuals or groups overseeing the 44 45 trial, if applicable (see Item 21a for data monitoring committee) on October 5, 2021 by guest. Protected copyright. 46 47 Introduction 48 49 Background and 6a Description of research question and justification for undertaking the 50 rationale trial, including summary of relevant studies (published and 51 （P5,P6,P7） unpublished) examining benefits and harms for each intervention 52 53 6b Explanation for choice of comparators 54 55 Objectives 7 Specific objectives or hypotheses 56 （P6,P7） 57 58 59 60

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1 2 Trial design 8 Description of trial design including type of trial (eg, parallel group, 3 （P7） crossover, factorial, single group), allocation ratio, and framework (eg, 4 superiority, equivalence, noninferiority, exploratory) 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 7 8 Methods: Participants, interventions, and outcomes 9 10 Study setting 9 Description of study settings (eg, community clinic, academic hospital) 11 （P9） and list of countries where data will be collected. Reference to where 12 list of study sites can be obtained 13 14 Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility 15 16 （P8,P9） criteria for study centres and individuals who will perform the 17 interventions (eg, surgeons, psychotherapists) 18 For peer review only 19 Interventions 11a Interventions for each group with sufficient detail to allow replication, 20 （P10,P11,P12,P1 including how and when they will be administered 21 3） 22 11b Criteria for discontinuing or modifying allocated interventions for a 23 given trial participant (eg, drug dose change in response to harms, 24 25 participant request, or improving/worsening disease) 26 27 11c Strategies to improve adherence to intervention protocols, and any 28 procedures for monitoring adherence (eg, drug tablet return, 29 laboratory tests) 30 31 11d Relevant concomitant care and interventions that are permitted or 32 prohibited during the trial 33 34 Outcomes 12 Primary, secondary, and other outcomes, including the specific 35 （P13,P14,P15,P1 measurement variable (eg, systolic blood pressure), analysis metric 36 37 6） (eg, change from baseline, final value, time to event), method of http://bmjopen.bmj.com/ 38 aggregation (eg, median, proportion), and time point for each 39 outcome. Explanation of the clinical relevance of chosen efficacy and 40 harm outcomes is strongly recommended 41 42 Participant 13 Time schedule of enrolment, interventions (including any run-ins and 43 44 timeline（P7） washouts), assessments, and visits for participants. A schematic 45 diagram is highly recommended (see Figure) on October 5, 2021 by guest. Protected copyright. 46 47 Sample size 14 Estimated number of participants needed to achieve study objectives 48 （P7,P8） and how it was determined, including clinical and statistical 49 assumptions supporting any sample size calculations 50 51 Recruitment 15 Strategies for achieving adequate participant enrolment to reach 52 53 （P9） target sample size 54 55 Methods: Assignment of interventions (for controlled trials) 56 Allocation: 57 58 59 60

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1 2 Sequence 16a Method of generating the allocation sequence (eg, computer- 3 generation generated random numbers), and list of any factors for stratification. 4 （P9） To reduce predictability of a random sequence, details of any planned 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 restriction (eg, blocking) should be provided in a separate document 7 that is unavailable to those who enrol participants or assign 8 interventions 9 10 Allocation 16b Mechanism of implementing the allocation sequence (eg, central 11 concealment telephone; sequentially numbered, opaque, sealed envelopes), 12 13 mechanism describing any steps to conceal the sequence until interventions are 14 （P9） assigned 15 16 Implementation 16c Who will generate the allocation sequence, who will enrol participants, 17 （P9） and who will assign participants to interventions 18 For peer review only 19 Blinding 17a Who will be blinded after assignment to interventions (eg, trial 20 (masking) participants, care providers, outcome assessors, data analysts), and 21 （P9,P10） how 22 23 17b If blinded, circumstances under which unblinding is permissible, and 24 25 procedure for revealing a participant’s allocated intervention during 26 the trial 27 28 Methods: Data collection, management, and analysis 29 30 Data collection 18a Plans for assessment and collection of outcome, baseline, and other 31 methods（P17） trial data, including any related processes to promote data quality (eg, 32 duplicate measurements, training of assessors) and a description of 33 34 study instruments (eg, questionnaires, laboratory tests) along with 35 their reliability and validity, if known. Reference to where data 36 collection forms can be found, if not in the protocol 37 http://bmjopen.bmj.com/ 38 18b Plans to promote participant retention and complete follow-up, 39 including list of any outcome data to be collected for participants who 40 41 discontinue or deviate from intervention protocols 42 Data 19 Plans for data entry, coding, security, and storage, including any 43 44 management related processes to promote data quality (eg, double data entry; 45 （P17） range checks for data values). Reference to where details of data on October 5, 2021 by guest. Protected copyright. 46 management procedures can be found, if not in the protocol 47 48 Statistical 20a Statistical methods for analysing primary and secondary outcomes. 49 methods Reference to where other details of the statistical analysis plan can be 50 51 （P18,P19） found, if not in the protocol 52 53 20b Methods for any additional analyses (eg, subgroup and adjusted 54 analyses) 55 56 20c Definition of analysis population relating to protocol non-adherence 57 (eg, as randomised analysis), and any statistical methods to handle 58 missing data (eg, multiple imputation) 59 60

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1 2 Methods: Monitoring 3 4 Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role

5 （P17,P18） and reporting structure; statement of whether it is independent from BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 the sponsor and competing interests; and reference to where further 7 8 details about its charter can be found, if not in the protocol. 9 Alternatively, an explanation of why a DMC is not needed 10 11 21b Description of any interim analyses and stopping guidelines, including 12 who will have access to these interim results and make the final 13 decision to terminate the trial 14 15 Harms（P17） 22 Plans for collecting, assessing, reporting, and managing solicited and 16 spontaneously reported adverse events and other unintended effects 17 18 Forof peer trial interventions review or trial conduct only 19 20 Auditing(P18) 23 Frequency and procedures for auditing trial conduct, if any, and 21 whether the process will be independent from investigators and the 22 sponsor 23 24 Ethics and dissemination 25 26 Research ethics 24 Plans for seeking research ethics committee/institutional review board 27 28 approval（P19） (REC/IRB) approval 29 30 Protocol 25 Plans for communicating important protocol modifications (eg, 31 amendments(P18) changes to eligibility criteria, outcomes, analyses) to relevant parties 32 (eg, investigators, REC/IRBs, trial participants, trial registries, journals, 33 regulators) 34 35 Consent or 26a Who will obtain informed consent or assent from potential trial 36 37 assent(P9) participants or authorised surrogates, and how (see Item 32) http://bmjopen.bmj.com/ 38 39 26b Additional consent provisions for collection and use of participant data 40 and biological specimens in ancillary studies, if applicable 41 42 Confidentiality 27 How personal information about potential and enrolled participants will 43 （P17,P18） be collected, shared, and maintained in order to protect confidentiality 44 before, during, and after the trial 45 on October 5, 2021 by guest. Protected copyright. 46 Declaration of 28 Financial and other competing interests for principal investigators for 47 interests（P23） the overall trial and each study site 48 49 Access to data 29 Statement of who will have access to the final trial dataset, and 50 51 （P23,P24） disclosure of contractual agreements that limit such access for 52 investigators 53 54 Ancillary and 30 Provisions, if any, for ancillary and post-trial care, and for 55 post-trial compensation to those who suffer harm from trial participation 56 care(P19) 57 58 59 60

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1 2 Dissemination 31a Plans for investigators and sponsor to communicate trial results to 3 policy（P20） participants, healthcare professionals, the public, and other relevant 4 groups (eg, via publication, reporting in results databases, or other 5 BMJ Open: first published as 10.1136/bmjopen-2019-036061 on 5 July 2020. Downloaded from 6 data sharing arrangements), including any publication restrictions 7 8 31b Authorship eligibility guidelines and any intended use of professional 9 writers 10 11 31c Plans, if any, for granting public access to the full protocol, participant- 12 level dataset, and statistical code 13 14 Appendices 15 16 Informed consent 32 Model consent form and other related documentation given to 17 materials participants and authorised surrogates 18 For peer review only 19 （P19） 20 21 Biological 33 Plans for collection, laboratory evaluation, and storage of biological 22 specimens specimens for genetic or molecular analysis in the current trial and for 23 future use in ancillary studies, if applicable 24 25 *It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 26 Explanation & Elaboration for important clarification on the items. Amendments to the 27 protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT 28 29 Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” 30 license. 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on October 5, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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