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Abstract

Background

Prior research has shown that home-based cardiac rehabilitation (HBCR) and center-based cardiac rehabilitation (CR) achieve comparable clinical outcomes in patients at low to moderate cardiovascular risk. However, the effectiveness of HBCR in high-risk patients remains uncertain. This study evaluates the efficacy of a DTx-integrated, multidisciplinary HBCR program as an alternative to usual care in high-risk patients following percutaneous coronary intervention (PCI).

Methods

The DTx-HBCR trial is a parallel-arm, randomized controlled trial that will enroll 366 high-risk patients undergoing PCI at West China Hospital of Sichuan University. Participants will be randomly assigned in a 1:1 ratio to either a 6-month DTx-HBCR group (intervention group) or a 6-month usual care group (control group). Following the intervention period, both groups will be observed for an additional 6-month follow-up without active intervention. Outcome assessments will be conducted at baseline and at 3, 6, and 12 months post-randomization. The primary outcome is the between-group difference in functional capacity at 6 months, assessed by the 6-minute walk test. Key secondary outcomes include changes in cardiovascular health metrics (i.e., smoking status, blood pressure, glycosylated hemoglobin, lipid profile, body mass index, and physical activity), health-related quality of life, psychological well-being, and adherence to evidence-based cardioprotective medications. All analyses will be conducted according to the intention-to-treat principle.

Conclusion

The DTx-HBCR trial is a novel randomized controlled clinical study designed to evaluate the efficacy of DTx-integrated HBCR program in improving functional capacity in high-risk patients following PCI. This DTx-integrated intervention has the potential to enhance cardiovascular health outcomes in this high-risk population.

Trial registration

NCT06542575 (ClinicalTrials.gov).

Keywords

Home-based cardiac rehabilitation digital therapeutics cardiovascular disease coronary heart disease percutaneous coronary intervention health technology secondary prevention

Introduction

Cardiovascular disease (CVD) continues to be the top cause of death globally, responsible for 32% of all fatalities.¹ Among the various forms of CVD, coronary heart disease (CHD) remains the most prevalent. The advent of percutaneous coronary intervention (PCI) has significantly improved survival outcomes in patients with CHD. However, despite these advances, approximately 20% of post-PCI patients experience subsequent cardiovascular events, including recurrent myocardial infarction, stroke, or cardiovascular mortality.² The need for sustained access to long-term secondary prevention and rehabilitation services has become increasingly critical.³ Cardiac rehabilitation (CR) is a cornerstone in the secondary prevention of CVD. Clinical practice guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommend CR for patients after myocardial infarction,^4,5 or coronary-artery revascularization by means of PCI.⁶ Participation in CR has been shown to reduce the risk of cardiovascular mortality and hospital readmissions, while simultaneously enhancing patients’ health-related quality of life (HRQoL) and functional capacity.^7,8 Despite substantial evidence supporting the clinical benefits and cost-effectiveness of CR, traditional center-based CR programs remain underutilized and inadequately accessible to all eligible patients.⁹ Therefore, there is a pressing need for scalable, accessible interventions to expand the reach and impact of CR.

Home-based cardiac rehabilitation (HBCR), which delivers core components of CR outside of conventional clinical settings, represents a promising strategy to overcome barriers associated with center-based programs and to enhance patient referral rates, participation, and adherence to secondary prevention measures.^10,11 A 2019 scientific statement from the American Association of Cardiovascular and Pulmonary Rehabilitation, the ACC/AHA, recommends HBCR referrals for clinically stable, low- to medium-risk patients who are eligible for CR but cannot access center-based programs.¹² Several updates of the Cochrane systematic review and meta-analysis of home versus center-based CR have shown that home-based models of CR achieve similar gains in patient efficacy to center-based programs.^13,14 Additionally, from the perspective of patients, implementing HBCR upon discharge is an accessible, cost-effective option for achieving health benefits.^15,16 It is important to note that the majority of multifaceted studies investigating HBCR have primarily focused on populations at low to moderate cardiovascular risk.¹² A recent systematic review assessing the safety of HBCR in 808 patients—over half of whom were at high risk for CVD—reported an initial incidence rate of serious adverse events as 1 per 23,823 patient-hours of HBCR exercise.¹⁷ These findings provide valuable evidence supporting the safety profile of HBCR in high-risk patient populations. Nevertheless, the evidence regarding the effectiveness of HBCR remains limited for high-risk, multimorbid, and complex CHD populations.

In recent years, digital therapeutics (DTx), an emerging branch of mobile health, has garnered increasing interest within the research community. DTx delivers holistic medical interventions to patients through evidence-based, technology-based software algorithms or applications, aimed at optimizing disease management, prevention, and treatment.¹⁸ In many countries, DTx are classified as novel medical devices, necessitating rigorous clinical evaluation and regulatory approval prior to market authorization.¹⁹ To date, DTx has shown promise in multifarious disease fields including cardiovascular,²⁰ neurological,²¹ psychological,²² and cancer disease,²³ resulting in better health status, symptom relief, medication adherence, and HRQoL. This suggests that integrating the HBCR program with high-quality, software-based DTx has the potential to deliver a more personalized and enhanced CR strategy tailored to the needs of patients with complex clinical profiles. Such an approach may also contribute to strengthening the evidence base for the effectiveness of HBCR in broader eligible populations, including individuals at high risk for CHD.

Herein, in this trial, we developed an interactive WeChat mini program, Huaxiaoxin, which functions as a medical device and is grounded in evidence-based core components of CR. These components include exercise training, risk factor management (e.g., lipid control, blood pressure regulation, diabetes management, and smoking cessation), psychosocial support, physical activity counseling, and nutritional guidance.²⁴ The trial aims to evaluate the efficacy of DTx-integrated HBCR using Huaxiaoxin in improving functional capacity, cardiovascular risk factor control, medication adherence, and HRQoL in high-risk patients undergoing PCI, compared with usual care.

Methods

Study design

The DTx-HBCR trial is a single-center, parallel-group, prospective randomized controlled clinical trial designed to evaluate high-risk patients with CHD following PCI. The trial will be conducted at West China Hospital, Sichuan University, China. The study protocol has been developed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines and will be conducted in compliance with the ethical principles set forth in the Declaration of Helsinki. A total of 366 eligible patients will be randomly assigned to either the DTx-HBCR group (intervention) or the usual care group (control), with both groups receiving a 6-month intervention. After the intervention phase, participants in both groups will enter a 6-month follow-up period without active intervention. Outcome assessments will be conducted at baseline (T0), 3 months (T1), 6 months (T2), and at the end of the 12-month follow-up period (T3) (Figure 1). All assessments will be performed by investigators blinded to group allocation.

Figure 1.

DTx-HBCR study flow diagram. PCI, percutaneous coronary intervention; HBCR, home-based cardiac rehabilitation; DTx, digital therapeutics; CR, cardiac rehabilitation; BP, blood pressure; ECG, electrocardiogram; BMI, body mass index; HRQoL, health-related quality of life.

Study objective

This study aims to evaluate the efficacy of a DTx-integrated HBCR program in improving functional capacity in high-risk patients following PCI, as measured by the 6-minute walk test (6MWT) at 6 months post-randomization.²⁵ Secondary objectives involve evaluating changes in cardiovascular health metrics [smoking, blood pressure (BP), glycosylated hemoglobin, lipids, body mass index (BMI), physical activity],²⁶ HRQoL, psychological status, and adherence to cardioprotective medications to explore the short- and medium-term effectiveness of DTx-integrated HBCR. Furthermore, the study will examine strategies to enhance participation and adherence to CR and will evaluate the cost-effectiveness of the intervention within this patient population.

Eligibility criteria

Eligible participants for enrollment in the DTx-HBCR trial are patients who have undergone successful PCI and meet the high-risk criteria, defined as having at least one high-risk clinical feature and one high-risk angiographic characteristic. Based on clinical experience and existing literature, “high-risk” patients are defined as those presenting with complex clinical and angiographic characteristics associated with an elevated risk of recurrent cardiovascular events and rehospitalization during follow-up.^27–29 All participants are required to possess a functional smartphone, have an active WeChat account, and be proficient in the Chinese language. Detailed inclusion and exclusion criteria are presented in Table 1.

Table 1.

Inclusion and exclusion criteria.

Inclusion criteria
To be eligible to participate in this study, a participant must meet all of the following criteria:
(1) Women or men, the ages of 18 and 75 years.
(2) A functional smartphone and an active WeChat account.
(3) Sufficient reading and writing language skills in Chinese.
(4) Be willing to participate the study and sign informed consent.
(5) Patients must have at least one clinical feature and one angiographic feature:
A. Clinical features: age ≥ 65 years, female sex, troponin positive acute coronary syndrome, established vascular disease (prior myocardial infarction, coronary revascularization or peripheral arterial disease), diabetes mellitus requiring medication and chronic kidney disease (estimated glomerular filtration rate < 60 ml/min/1.73 m² or creatinine clearance < 60 cc/min).
B. Angiographic features: multivessel coronary artery disease, total stent length > 30 mm, thrombotic target lesion, bifurcation lesion requiring two stents, obstructive left main or proximal left anterior descending lesion, and calcified target lesion requiring atherectomy.
Exclusion criteria
A potential participant who meets any of the following criteria will be excluded from participation in this study:
(1) Contraindications to exercise rehabilitation (e.g., untreated ventricular tachycardia, severe heart failure (New York Heart Association class III or IV heart failure, or ejection fraction < 40%), uncontrolled hypertension or hypotension, active hemorrhage, severe liver failure, significant exercise limitations).
(2) Vision, hearing, cognition-related, or mental impairment leading to inability to cooperate.
(3) Patients with established planned Phase II percutaneous coronary intervention.
(4) Having a pre-existing comorbid disease with a life expectancy of < 1 year.
(5) Poor compliance and unable to complete the expected follow-up.
(6) Unable to access WeChat via a smartphone after training.

Intervention (DTx-HBCR group)

In the DTx-HBCR group, patients receive the HBCR program via the Huaxiaoxin WeChat mini program. The Huaxiaoxin WeChat mini program, developed by the Huaxiaoxin Health Management Team, will be deployed under the oversight of the Department of Cardiology at West China Hospital, Sichuan University, China. This interactive program, classified as a medical device, integrates evidence-based core components of CR as recommended by clinical guidelines for post-PCI patients. It is founded on principles of behavioral change and cardiovascular health promotion, incorporating functionalities such as goal setting, prompts, visualizations, and real-time feedback (Figure 2).²⁴ The WeChat mini program comprises two primary components. The first component encompasses a range of interventions, including exercise training, education, and cardiovascular risk factor management. The second component offers a secure platform for personalized feedback, real-time communication, remote data sharing, and access to relevant files for both patients and healthcare professionals throughout the 12-month study period. Participants allocated to the intervention group will undergo a 6-month HBCR program, delivered via the Huaxiaoxin WeChat mini program. This program includes an intensive 3-month phase followed by a 3-month step-down phase. The comprehensive intervention package consists of the following elements (Figure 3):

Figure 2.

Components of the Huaxiaoxin WeChat mini program. Huaxiaoxin WeChat mini Program components include (1) patient own smartphone and a WeChat account, (2) Smart devices (bluetooth-enabled blood pressure and electrocardiogram monitor), (3) scheduled feedback calls, (4) a clinician dashboard and specified phone for contact, and (5) just-in-time two-way online communication.

Figure 3.

Huaxiaoxin WeChat mini program. Shown vividly here are various contents and tabs within the WeChat mini program, including vitals, medication tracking, exercise training, educational program, real-time feedback, and online counseling.

Role of a multidisciplinary team

Patient evaluation is conducted by a multidisciplinary care management team comprising cardiologists, case managers, exercise physiotherapists, dietitians, and psychologists. Each team member assumes specific responsibilities within the study, as outlined below: (1) case managers, who are registered nurses, are responsible for participant enrollment, data collection, monitoring physical activity, ensuring medication adherence, and tracking key cardiovascular health indicators (e.g., BP, heart rate, test results, BMI, and tobacco use); (2) cardiologists play a central role in patient assessment, referral to cardiac rehabilitation, interpretation and adjustment of cardioprotective medications, management of treatment-related side effects, and evaluation of symptoms such as chest pain; (3) exercise physiotherapists develop individualized exercise prescriptions and lead training sessions aimed at promoting independent physical activity and enhancing patients’ self-efficacy; (4) dietitians and psychologists provide dietary counseling and psychological support, respectively, through scheduled telephone follow-ups—biweekly during the initial 3 months and monthly over the following 3 months.

Individualized exercise prescription

In accordance with guideline recommendations,³⁰ the exercise prescription includes exercise training supplemented with strengthening training. Specifically, the aerobic exercise training protocol incorporates four components: modalities: brisk walking, jogging or cycling; duration: 30–60 minutes session and each session includes a 5–10 minute warm-up and 10 minute cool-down before and after exercise; frequency: 3–5 days per week; intensity: moderate intensity is mainly recommended (determined by the rating of perceived exertion of 12 or 13 on the 6–20 Borg Scale). For selected patients with adequate tolerance, resistance training is recommended as a supplementary component, typically performed on 1–2 nonconsecutive days per week. Each session should consist of 2–4 sets, with 10–15 repetitions per set. Recommended modalities include the use of dumbbells, resistance bands, and weight machines. Throughout the exercise, a portable electrocardiogram (ECG) monitoring device (Hangzhou Proton Technology Co., Ltd) provided for the study continuously recorded the patient's ECG signals and synchronized the data with the Huaxiaoxin platform. The exercise prescription is progressively formulated and adjusted based on the patient's condition, symptoms, and ECG changes with exercise, as well as repeated 6MWT and rating of perceived exertion on the Borg Scale at on-site follow-up visits. To this end, patients receive individualized coaching and feedback on their training through weekly telephone consultations during the first month. The frequency of these consultations is subsequently reduced to biweekly during months 2–3 and then to monthly from month 4 onward, with the aim of facilitating adherence and supporting progressive achievement of personalized training objectives. To enhance patent adherence and behavior change, the principles of goal-setting theory and motivational interviewing are employed during the intervention.^31,32 Crucially, patients are advised to seek immediate medical attention by contacting their healthcare providers, calling emergency services (e.g., 120), or presenting to the emergency department upon the onset of any concerning or potentially life-threatening symptoms.

Educational program

The educational program is structured into three distinct modules: disease education, home rehabilitation, and expert-led lectures. Together, these modules offer a comprehensive framework for the management of CHD, addressing key areas such as risk factor education, management of common comorbidities including diabetes mellitus and hypertension, pharmacological mechanisms and associated adverse effects, nutritional guidance, smoking cessation, and psychological support. Educational materials are delivered via concise video segments and illustrated text formats, aiming to improve patients’ self-management competencies and facilitate sustained behavioral changes conducive to long-term disease control and health maintenance. Patients are encouraged to engage with the educational sessions on a weekly basis, tailored to their individual learning capacity and personal schedule, with the goal of completing the entire program within a 3-month period. Following hospital discharge, behavioral feedback will be provided regularly through weekly telephone consultations or via the Huaxiaoxin platform during the first month. This frequency will be reduced to biweekly consultations during months 2–3, and subsequently to monthly consultations from months 4 to 6, in order to reinforce engagement and support sustained behavioral progress. Additionally, the program provides additional education as necessary to ensure continuous support and guidance.

BP monitoring and management

All eligible patients will receive a Bluetooth-enabled BP monitoring device (BP2, LEPU Medical Technology Co., Ltd) to measure their BP twice daily at home. The BP readings will be transmitted in real time to the Huaxiaoxin program, where they can be accessed by individuals and reviewed by care managers on a weekly basis during the intensive phase and biweekly during the step-down phase. Individualized feedback and guidance will be given after each data review,³³ and an alarm system will be automatically activated when BP readings exceed a threshold (≥140/90 mmHg), alerting both the patient and the case managers with a red warning sign, meanwhile. Subsequently, case managers will initiate follow-up contact with patients via telephone or the digital platform to prompt repeat BP measurements. If clinically indicated, a referral for cardiology consultation will be arranged to provide appropriate medical guidance. Additionally, any inquiries related to the use of medical devices or operational concerns will be addressed through the platform-based consultation service.

Cardiovascular risk factors modification

Baseline assessment of patient data related to cardiovascular health, including blood pressure, blood glucose, lipid profiles, BMI, surgical and medication history, comorbidities, tobacco use, and dietary habits, will be conducted to individualize target levels for risk factor control. These data will then be transferred to the Huaxiaoxin program platform, which not only stores the information but also displays the trends of all metrics and provides alert notifications and recommendations based on the range of measures for patients. Both patients and clinicians (or case managers) will have access to updated information regarding disease progression and risk factor status, enabling iterative re-evaluation and targeted modification of individual risk factors.

Long-term medication management

At baseline, care managers conduct a comprehensive review and documentation of all cardioprotective medications and concomitant therapies prescribed for comorbid conditions, including details such as drug class, dosage, and administration frequency. Any medication adjustments, including dose reduction, dose increase, discontinuation, and the addition of new medications, as well as any adverse drug reactions, will be recorded in the Huaxiaoxin program. The 8-item Morisky Medication Adherence Scale will be administered to identify patients with poor medication adherence, allowing timely education and encouragement.³⁴ Patients are provided with educational videos to enhance their understanding of medication effects and commonly associated side effects. Additionally, they have continuous access to physicians for timely consultation and medical guidance.

Usual care (control group)

Patients in the control group receive usual CR care, as routinely provided in clinical practice. Prior to hospital discharge, they will participate in a structured, in-person pre-discharge preparation session. Upon completion of a clinical evaluation by a cardiologist, a physiotherapist will conduct an exercise capacity test (i.e., 6MWT) to prescribe structured exercise protocol (including frequency, intensity, time and type) consistent with the protocol employed in the intervention group. Subsequently, nurses will deliver comprehensive CR guidance, including detailed instructions on the prescribed exercise protocol, education on medication adherence, and counseling on risk factor modification, such as smoking cessation, lifestyle adjustments, and dietary management. In addition, they will assist patients in uploading relevant data to the Huaxiaoxin platform. Participants in the control group will be permitted to access the Huaxiaoxin program; however, the platform will function solely as a data repository without offering active feedback or CR-related interventions.

After discharge, patients will have follow-up visits at the Outpatient Department at 1, 3, 6, and 12 months. During each visit, the cardiologist will reassess the patient's clinical status and provide feedback on changes in cardiovascular health metrics (such as smoking, BP, glycosylated hemoglobin, lipids, BMI, physical activity), HRQoL, psychological status, and adherence to essential cardioprotective medications. Concurrently, the physiotherapist will re-assess exercise capacity to optimize the individualized exercise prescription. Nurses will deliver continued guidance to enhance patient adherence to the exercise protocol and to reinforce health education. This CR care management approach aims to ensure ongoing support and foster improvements in health outcomes among patients in the usual care group.

Measures and assessment

Sociodemographic and clinical data will be extracted from the hospital's electronic system at baseline. Data on cardiovascular risk factors (smoking, BP, glycosylated hemoglobin, lipids, BMI), along with standardized questionnaires assessing physical activity, HRQoL, psychological status (depression and anxiety), and medication adherence, will be collected via the Huaxiaoxin data platform at enrollment and during follow-up visits. Information on major adverse cardiovascular events (MACEs) will also be collected during scheduled visits to the hospital and monthly telephone calls with the patients.

Functional capacity will be evaluated by trained physiotherapists, who are blinded to randomization, using the standardized 6 MWT protocol conducted in the clinical rehabilitation room. Participant satisfaction with the Huaxiaoxin software will be collected from the intervention group at 6 months post-randomization. Table 2 presents a comprehensive overview of the measures employed.

Table 2.

Baseline and outcome assessment.

Outcome	Measures and assessment	Baseline	3-month	6-month	12-month
Primary outcome
Functional capacity	6MWT	✓		✓
Secondary outcomes
Functional capacity	6MWT		✓
HRQoL	Seattle Angina Questionnaire⁴⁰ and EuroQol 5-Dimension Questionnaire⁴¹ implemented via H_EDP	✓	✓	✓	✓
Blood pressure	Obtained from H_EDP (Systolic and diastolic blood pressure averaged over 2 measurements measured at enrollment and follow-up visits)	✓	✓	✓
Body mass index	Derived from height and weight from H_EDP (measured at enrollment and follow-up visits of the study	✓	✓	✓
Glycosylated hemoglobin	Obtained from H_EDP (measured at enrollment and follow-up visits of the study	✓	✓	✓
Smoking habits	Obtained from H_EDP (smoking stage of change and number of smokes/day)	✓	✓	✓	✓
Blood lipid profile	Obtained from H_EDP (measured at enrollment and follow-up visits of the study	✓	✓	✓	✓
Depression	9-item Patient Health Questionnaire⁴² implemented via H_EDP	✓	✓	✓
Anxiety	7-item Generalized Anxiety Disorder questionnaire⁴³ implemented via H_EDP	✓	✓	✓
Physical activity	International Physical Activity Questionnaire⁴⁴ implemented via H_EDP	✓	✓	✓
Medication adherence	8-item Morisky medication adherence scale³⁷ implemented via H_EDP	✓	✓	✓	✓
Safety	AEs collected at follow-up visits and monthly telephone calls with the participants	✓	✓	✓	✓
Exploratory outcomes
MACEs	Registered and censored at follow-up visits and monthly telephone calls with the participants.	✓	✓	✓	✓
User satisfaction (for the Intervention group only)	System Usability Scale⁴⁵ implemented via H_EDP			✓

6MWT, 6-min walk test; HRQoL, health-related quality of life; H_EDP, Huaxiaoxin electronic data platform; AEs, adverse events; MACEs, major adverse cardiovascular events.

Study outcomes

The primary outcome is the change in functional capacity, as measured by the 6MWT, comparing the distance walked between the DTx-HBCR and usual care groups at 6 months post-randomization. The 6MWT is a widely recognized clinical test for evaluating functional capacity in individuals with cardiovascular disease.^35,36 Secondary outcomes include change in functional capacity at 3 months after randomization, and change in conventional CVD risk factors, such as lipid profile, glycosylated hemoglobin, BMI, BP, and smoking habits at 3 and 6 months post randomization. Other secondary outcomes incorporate changes in several indicators at 3 and 6 months post randomization, including in HRQoL, as assessed by the Seattle Angina Questionnaire³⁷ and the EuroQol 5-Dimension Questionnaire³⁸; depression scores, as assessed by the 9-item Patient Health Questionnaire³⁹; anxiety scores, as assessed by the 7-item Generalized Anxiety Disorder questionnaire⁴⁰; physical activity levels, and medication adherence, as assessed by the International Physical Activity Questionnaire⁴¹ and the 8-item Morisky Medication Adherence Scale,³⁴ respectively. Additionally, adverse events (AEs) such as palpitations, chest pain, dyspnea, syncope, cardiac arrest, and death occurring during exercise testing or training will be classified as safety outcomes.

Other pre-specified outcomes include MACEs, defined as a composite of cardiac death (i.e., all deaths with a clearly cardiovascular or unknown cause will be classified as cardiac, whereas non-cardiac deaths will require documentation of a non-cardiac etiology), nonfatal myocardial infarction, nonfatal stroke, and target vessel revascularization. These events will be monitored during scheduled visits and through monthly telephone follow-ups with participants throughout the study. In addition, user satisfaction with the Huaxiaoxin program will be evaluated using a modified version of the System Usability Scale (Table 2).⁴²

Sample size determination

The SMART-CR/SP study⁴³ aimed to evaluate the effectiveness of a smartphone-based CR program delivered via the social media platform WeChat. The study reported that the improvement in 6-minute walk distance (6MWD) at 6 months was significantly greater in the SMART-CR/SP group compared to the control group (543.4 ± 67.5 m vs 523.5 ± 60.2 m). The sample size estimation for the present study is based on this primary effectiveness endpoint. Drawing on the SMART-CR/SP study, it is assumed that at 6-month follow-up, the mean 6MWD will be 523.5 ± 60.2 m in the control group and 543.4 ± 67.5 m in the DTx-HBCR group. Using two-sample t-tests allowing for unequal variances in PASS 2023, with a two-sided α of 0.05 and 80% statistical power, the required sample size is 164 participants per group, yielding a total of 328. Allowing for a 10% dropout rate, the final target sample size is 366, with 183 participants in each group.

Recruitment

Potential participants will be identified through a two-step screening process, which includes an initial review of the hospital's electronic medical records followed by an assessment of inpatient documentation conducted by the study team. This process will verify qualifying diagnoses, assess patient needs, and determine the feasibility and appropriateness of HBCR for each individual. The initial interview typically occurred in the hours following the PCI procedure to optimize engagement. Following assessment against exclusion criteria, eligible patients are approached prior to discharge to obtain written informed consent. Comprehensive baseline sociodemographic and clinical data from consenting participants are systematically collected and recorded by two specialist nurses who have completed standardized training.

Randomization

Eligible patients who gave informed consent will be randomized at a 1:1 ratio, stratified by age (≥65 years or < 65 years), to either the 6-month DTx-HBCR group or the 6-month usual care group through a centralized computerized allocation system. Following the initial intervention period, both groups will undergo an additional 6 months of follow-up without any further intervention. Patients will be notified of their group allocation upon logging into the Huaxiaoxin WeChat mini program and will subsequently receive a concise video outlining the operational procedures of the program. Supplementary technical training will be provided upon patient request.

Blinding

Blinding of study team members involved in patient enrollment and of participants themselves is challenging due to the inherent nature of the intervention. To minimize potential bias, participants will be advised not to discuss their group allocation or participation in the trial with one another. Clinical researchers will follow the study protocol rigorously to maintain standardization across all study procedures. Blinding will be maintained at the level of outcome assessment. Individuals responsible for data management and statistical analysis will be independent of the clinical conduct of the trial and will remain blinded to group allocation throughout the study.

Data collection and management

Each patient has a unique hospitalization registration number that can only be identified. Patient data will be recorded and collected by designated case managers using standardized, preprinted paper case report form (CRF) in conjunction with Huaxiaoxin's backend electronic data platform. This platform allows data to be retrieved directly from the hospital's electronic information system for storing data at baseline and the follow-up period, while all questionnaires are also implemented and recorded on the platform. Patients who withdraw from the study at any time and for any reason will not be replaced; every effort will be made to contact them and obtain the necessary information. Case managers will meticulously review all data entries before validation, addressing any missing data through additional inquiries.

Statistical analyses

All statistical analyses will be conducted by an independent statistician. The intention-to-treat (ITT) analysis will be the primary approach, though participants who are discontinued due to adverse events or non-engagement will be excluded from the ITT analysis. Continuous variables will be described as the mean or median (interquartile range) and compared using the t-test or Mann–Whitney U test if the data are not normally distributed. Categorical data will be analyzed using the chi-square (or Fisher exact) test and presented as percentages. The primary and secondary outcomes will be compared between the intervention and control groups. To assess correlation strengths over different time points within the observation period, linear regression analysis will be conducted to determine independent predictors of baseline 6MWD. Potential confounders and baseline values of the dependent variables will be included as covariates. The Kaplan–Meier method will be employed to estimate the 12-month risk of MACEs, with comparisons between groups conducted using the log-rank test. A Cox proportional hazards model adjusted for covariates is used to analyze the relationship between several variables and MACEs, and the hazard ratio and associated 95% confidence interval will be calculated. A two-tailed P value less than 0.05 will be considered statistically significant for all analyses. Statistical analyses will be conducted using SPSS (version 26.0).

Cost-effectiveness analyses

An economic evaluation will be undertaken using cost-effectiveness analysis, wherein health outcomes will be quantified as quality-adjusted life years (QALYs). QALYs, serving as a standardized metric for health benefit, will be derived from changes in EuroQol 5-Dimension scores between baseline (T0) and study completion (T3).⁴⁴ All costs associated with the cardiological diagnostic and therapeutic process, from study enrollment to the end of follow-up, will be included. Care utilization data will be collected via the CRF during scheduled follow-up visits and monthly phone calls with patients. The cost categories will cover all direct costs, both within and outside the healthcare system, including outpatient visits, cardiac-related tests, diagnostics, and therapeutic procedures. Direct nonmedical costs will include travel and time costs for patients related to visits to the clinician and healthcare organization. Cardioprotective medications will be excluded from the analysis, as all patients receive consistent cardiology care. The incremental cost-effectiveness ratio will be determined using medical costs and health outcomes to assess the cost-effectiveness between the intervention and control groups. Sensitivity analyses will be performed to evaluate the robustness of the findings in relation to key assumptions and parameter variations. Furthermore, a Markov model will be developed to facilitate long-term economic evaluations beyond the trial horizon.⁴⁵

Data monitoring

At our hospital, an independent Trial Steering Committee will provide overall supervision and governance of the trial, ensuring adherence to the protocol, monitoring its progress, and making key decisions regarding trial design and modifications. Additionally, a Data Safety and Monitoring Committee, an independent group from the sponsor, the investigators and the Steering Committee, is responsible for overseeing the safety and outcome data of participants in the trial.

Adverse events

AEs will be systematically monitored during scheduled follow-up visits and monthly telephone interviews with participants. Spontaneously reported AEs by participants or caregivers will be evaluated via telephone by trained study personnel, who will also coordinate appropriate medical care as needed. Each AE will be documented with respect to its nature, onset, duration, severity, and potential relation to the intervention. Serious AEs deemed study-related will be promptly reported to the Research Ethics Committee in accordance with regulatory timelines. The classification of AEs will be reviewed by the principal investigator and a panel of experts, using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

Ethics and dissemination

Ethical approval for the study was granted by the Biomedical Research Ethics Committee of West China Hospital (2024 Review No. 151), and the study was registered with ClinicalTrials.gov (Identifier: NCT06542575). This protocol is version 3.0 dated 10 April 2024. Written informed consent will be obtained prior to participant enrollment. Researchers must follow ethical criteria designed to protect participants from harm, ensure informed and deliberate consent, guarantee voluntary participation, uphold standards of confidentiality, and ensure anonymity in the presentation of study results. The study report will align with the Consolidated Standards for Reporting Trials (CONSORT) 2010 Statement⁴⁶ and will be disseminated through scientific platforms such as peer-reviewed journals.

Discussion

CR and secondary prevention are a Class I recommendations for managing patients with CHD from the ACC/AHA.⁶ Unfortunately, the utilization of CR remains suboptimal.^47,48 Over the past few decades, the model of CR has gradually transitioned from center-based CR to HBCR. HBCR programs incorporating technology tools are regarded as novel potential delivery strategies but are still in their infancy, with limited clinical data available for several subgroups, such as high-risk populations like individuals with complex comorbidities.⁴⁹ Further research is warranted to evaluate whether technology-assisted HBCR demonstrates comparable efficacy and safety across diverse populations, and whether it yields sustained improvements in engagement, adherence, and clinical outcomes among patients with CHD. The DTx-HBCR trial aims to incorporate novel components into the existing HBCR program to enhance the evidence base supporting HBCR as a viable alternative rehabilitation strategy.

Digital health is poised to remain a cornerstone of modern medicine, as technological integration into daily life continues to advance healthcare delivery. A key area within digital health is DTx, which combines advanced technology-based software algorithms or apps with the best practices on design, clinical support, usability, and data security.⁵⁰ As digital technology, DTx products are presented as high-quality software, including many subtypes such as web-based applications, mobile applications on smart devices, virtual reality, and video games.¹⁹ A randomized controlled trial involving the novel DTx smartphone app, HERB Mobile, integrated advances in behavioral science, and demonstrated significant clinical efficacy in reducing 24-hour ambulatory, home, and office BP when used in conjunction with standard lifestyle modification.⁵¹ WeChat mini programs are similar to general apps but don't require installation on smartphones. Their potential for widespread access is significant, as they can easily reach more WeChat users due to their convenience, accessibility, and low cost. WeChat mini programs designed to facilitate cardiovascular health interventions in rehabilitated patients with CVD have shown substantial promise as platforms for delivering CR.⁵² For example, a randomized controlled trial evaluating a combined smartphone- and WeChat-based CR and secondary prevention intervention demonstrated significant enhancements in functional capacity among individuals with CHD.⁴³ Considering this, the current DTx-HBCR trial will develop and evaluate a WeChat mini program-based intervention for cardiovascular health promotion in daily life, testing its effectiveness and feasibility in high-risk post-PCI patients who have limited access to home-based rehabilitation services. The integration of DTx and the core components of modern HBCR may establish a novel personalized delivery model for CR. This approach has the potential to address complex clinical scenarios and enhance patient acceptance of CR, thereby facilitating improved diagnosis, treatment, management, and prevention of disease in patients undergoing PCI through the daily utilization of smartphones and WeChat mini programs. Furthermore, the utilization of behavior change strategies such as goal setting, telemonitoring and motivational feedback has been identified as a beneficial component of effective digital technology-enabled CR interventions.^53,54 Among providing individualized CR in a home environment, this study highlights the importance of integrating comprehensive behavior change strategies (e.g., data uploading, telemonitoring, content visualizations, motivational feedback, and social support) to sustain patient engagement with the Huaxiaoxin program. In addition, Nurses, as skilled primary care providers, are well-equipped to work with patients of diverse needs and preferences, playing a crucial role in identifying challenges and collaborating with patients remotely.⁵⁵ During the study intervention, nurses as case managers will primarily provide motivational feedback and social support in setting goals and action plans for behavior modification through two-way communication and interaction with patients on the WeChat mini program platform.

Limitations

Our study design has several potential limitations. Firstly, patients with acute myocardial infarction who require urgent interventions may exhibit clinical characteristics distinct from those with stable CHD. Although the enrollment of high-risk post-PCI patients may reduce this disparity, subgroup or interaction analyses based on CHD type (acute versus chronic) may be necessary to evaluate differential effects on study outcomes. Second, the trial itself is a single-center randomized controlled clinical trial, which may diminish the representativeness of the sample and generalizability of the findings. We will rigorously comply with the protocol on the course of recruitment, randomization, and follow-up to minimize bias. Third, the Huaxiaoxin program is a comprehensive intervention based on WeChat. Operating properly in daily life could be challenging for some patients with relatively lower literacy levels and advanced age. Accordingly, participants will be provided with comprehensive training videos from the Huaxiaoxin program detailing the use of the intervention. Supplemental assistance will be made available as required, and the involvement of family members will be encouraged to promote greater engagement and compliance.

Conclusion

The DTx-HBCR trial will evaluate the safety and effectiveness of a new, multidisciplinary, DTx-integrated HBCR program over 12 months in improving functional status, cardiovascular risk factors, and CR participation in high-risk PCI patients, while also exploring its short- and medium-term outcomes. The results of the trial could help provide further evidence and justification that DTx-integrated HBCR is a valuable alternative for patients with CHD and even for those at relatively high risk. This is likely to translate into expanded coverage of CR delivery, better patient outcomes, and a reduced financial burden of CVD on healthcare systems.

Footnotes

Acknowledgements

The authors would like to thank the members of the health management team at the West China Hospital of Sichuan University for designing and developing the Huaxiaoxin WeChat mini program in this study.

ORCID iD

Shuangliang Ma

Ethical considerations

The clinical trial has been approved by the Biomedical Research Ethics Committee of West China Hospital (2024 Review No. 151), and the protocol was recorded in ClinicalTrials.gov (NCT06542575).

Author contributions

SM and ZC contributed to the design of the study, and the content and format of the protocol; SM and JZ contributed to the drafting and revision of the manuscript; YH, CL, MW, and YC contributed to the revision of the manuscript; ZC, JZ, JL, and LX contributed to the data collection of the trial; BH and MZ contributed to the drawing of the chart; HW and YC contributed to the data management of the study; CL contributed to the preparation of the registration of the trial. YH is responsible for the overall content, including the final work and/or the conduct of the study, and controls the decision to publish. All authors reviewed and approved the final version of the manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Sichuan Provincial Department of Science and Technology Natural Science Foundation Youth Fund Project, Key Research and Development Programs of Sichuan Province, (grant number 2024NSFSC1713, 2023YFS0177).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

YH.

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Evaluation of the efficacy of integrating digital therapeutics with home-based cardiac rehabilitation on cardiovascular health in high-risk post-PCI patients (DTx-HBCR): Study protocol for a randomized controlled trial

Abstract

Background

Methods

Conclusion

Trial registration

Keywords

Introduction

Methods

Study design

Study objective

Eligibility criteria

Intervention (DTx-HBCR group)

Role of a multidisciplinary team

Individualized exercise prescription

Educational program

BP monitoring and management

Cardiovascular risk factors modification

Long-term medication management

Usual care (control group)

Measures and assessment

Study outcomes

Sample size determination

Recruitment

Randomization

Blinding

Data collection and management

Statistical analyses

Cost-effectiveness analyses

Data monitoring

Adverse events

Ethics and dissemination

Discussion

Limitations

Conclusion

Footnotes

Acknowledgements

ORCID iD

Ethical considerations

Author contributions

Funding

Declaration of conflicting interests

Guarantor

References