Study design

In order to assess the effectiveness of a home-based personalised training module in addition to centre-based CR to improve habitual PA levels of CAD patients, an 18-week randomised controlled trial with four arms will be performed. Participants will be randomised into four groups as described in table 1.

Study setting and recruitment

Participants will be recruited from a large hospital (Canisius Wilhelmina Ziekenhuis) in the south-eastern part of the Netherlands. The hospital offers an outpatient CR programme with a supervised exercise training programme of 6 weeks. Patients who are invited to participate in CR are screened for inclusion criteria and informed about the study by the specialised CR nurse. Hereafter, a detailed participant information sheet and informed consent form will be handed over. During the CR orientation visit, which is planned within 1–3 weeks after CAD diagnosis, eligible patients will be approached by a member of the research team. Additional information regarding the study will be provided and obligations of the participant will be clearly explained once more. If the patient is willing to participate in the study and deemed eligible, an informed consent form is signed. Figure 1 presents the timeline of participants during the study.

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Figure 1

Flowchart, illustrating randomisation and measurements. CR, cardiac rehabilitation.

In order to be eligible to participate in this study, a subject need to meet all of the following inclusion criteria: participants must be (1) older than 18 years of age, (2) diagnosed with CAD (ST-elevation myocardial infarction—non-ST-elevation myocardial infarction—unstable angina pectoris—stable angina pectoris), (3) able to use a smartphone with the Virtual Training application, (4) referred to CR, (5) able to understand and perform the study procedures. Exclusion criteria are (1) being not in the possession of a smartphone, or being unable to operate a smartphone for the purpose of the trial (because of vision, hearing and cognitive or dexterity impairment), (2) having no (mobile) internet access at their place of residence, (3) having contraindications to perform exercise during the rehabilitation programme, (4) subjects who have severe orthopaedic problems that restricts PA, (5) having a significant language barrier.

Randomisation

After signing informed consent, subjects will be randomly assigned to one of the four training intervention groups. We will use software (Castor EDC 2021, Ciwit B.V., Amsterdam, The Netherlands) with a variable block randomisation to allocate the included patients to one of the four treatment arms, stratified by index diagnosis (acute event vs elective procedure) to ensure all groups have equal amounts of CVD type. There is no blinding after randomisation due to the nature of the intervention, making it impossible to blind the participants or the research team.

Usual care

All patients will receive usual care and will be seen by their cardiologist as clinically appropriate. Usual care consists of a 6-week comprehensive CR programme. Before, during and after the CR programme, regular individual consultations are scheduled with the CR nurse focussing on lifestyle improvement, medication adherence and psychosocial well-being. The nurses contributing to the secondary prevention programme are registered nurses with experience in the care of cardiac patients. Prior to participation in the CR programme, all patients undergo a bicycle cardiac stress test to assess exercise tolerance and detect abnormalities followed by an appointment with their cardiologist. Within the usual care CR programme, group sessions are focused on exercise under the supervision of a physiotherapist. These group sessions of approximately 1 hour take place two times a week for a duration of 6 weeks. If indicated, the standard CR programme can be extended by a dietary module, psycho-educative prevention module and psychological module or by additional consultations with the CR nurse.

Home-based program

Subjects in the home-based groups CR+, +CR and +CR+ will be instructed to perform daily physical activities in their home situation using the Virtual Training mHealth smartphone application (Welfaster ApS, Esbjerg, Denmark) (figure 2). The application is able to show different training programmes including both strength and aerobic exercises, such as squats, walking, running and provides instructions in the form of both video, text and audio during the exercises. At baseline, the researcher will guide the participant to set goals based on preferences and physical status, and subsequently construct a personalised home-based training programme. Goal setting is based on exercise preference (ie, biking more enjoyable then walking) and physical limits based on previous exercise experience, age and possible orthopaedic limitations. The training programme consists of a combination of aerobic and resistance exercises. Progression regarding intensity and feasibility of the exercises will be monitored with a weekly text message in the application. A reminder will be sent automatically after missing three subsequent training days. Patients can also contact the research team by sending an in-application message in the Virtual Training application. Aerobic exercises consist of an incremental walking, biking or running training programme with the goal to increase daily PA duration. Patients are encouraged to exercise daily, starting at a low intensity and duration and gradually increase duration and distance. Aerobic exercises start at 5–10 min and gradually increase to >30 min per day. Resistance exercises consist of 5–10 bodyweight exercises focussing on both upper and lower body which patients can perform in their home environment. Exercises are performed in 1–3 sets consisting of either 10–15 repetitions or are timebound (ranging from 30 to 120 s). Subjects will be instructed to perform the bodyweight exercises at least two times a week on a self-chosen moment using the Virtual Training application. During the centre-based rehabilitation period (weeks 1–6), the intensity of the home-based exercises will be adjusted to the patient’s physical status and level of PA. In the beginning, the strength exercise programme will consist of lighter exercises and longer breaks. Compliance will be monitored via the Virtual Training application and patients receive a weekly text message to ask about the intensity of the programme and whether it is needed to make adjustments to the training schedule. Based on the individual participants progression, the intensity of exercises and total training programme will be increased over time.

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Figure 2

Example of the front-end of the virtual training application.

Outcome measures

The primary outcome of the Cardiac RehApp study will be objectively measured habitual PA levels expressed in time spent on moderate to vigorous intensity activities (min/week). Secondary outcome parameters include total sitting time (min/week), physical fitness (estimated VO₂max), handgrip strength, CV risk profile, quality of life and cardiac anxiety scores. All participants will be assessed during three different timepoints: at baseline (prior to the CR programme T=0), after completion of the 6-week CR programme (T=1) and after 12 weeks of CR extension or usual care (ie, self-guidance, T=2) (figure 1). Outcome measures will be conducted at the same hospital.

Habitual PA

PA patterns will be objectively measured with a validated accelerometer (ActivPAL micro, PAL technologies, Glasgow, UK).10 11 The ActivPAL is a small device (25×45×5 mm), which is attached to the thigh by one of the researchers using hypoallergenic and transparent tape (Tegaderm, 3M), and collects data about static and dynamic acceleration as well as posture at a sampling rate of 20 Hz. To allow for continuous monitoring, the ActivPAL is sealed with a nitrile sleeve and transparent tape for waterproof protection. The monitor is worn for eight consecutive days for 24 hours per day. During these measurements, patients are required to fill in a sleep diary. After wearing the ActivPAL for eight consecutive days, the ActivPAL will be send back to our institute by registered mail parcel. The raw data will be extracted using the PAL Software Suite V.8 and analysed by a modified version of the script of Winkler et al using sleep/wake diaries.12 Sedentary time will be defined as any waking behaviour characterised by an energy expenditure ≤1.5 MET13 while in a seated, reclined or lying posture.14 15 The accumulation of sedentary time will be defined as short (<5 consecutive minutes), medium (5–29 consecutive minutes) and prolonged (≥30 consecutive minutes) sedentary bouts. Light intensity PA will be defined as standing time combined with stepping time with MET-values <3. Moderate-to-vigorous PA will be defined as stepping time with MET-values ≥3.16

Physical fitness

A submaximal cycling test will be performed to examine physical fitness, expressed as estimated maximal oxygen consumption. The Astrand-Rhyming test is a frequently used single-stage cycle ergometer test.17 In short, subjects perform a 6-min cycling test, preceded by a 4–5 min warm-up phase. After the 4–5 min warming-up period patients cycle for 6 min on a stable workload while heartrate is monitored continuously and the Borg score is noted during the 3rd and 6th minute. After warming-up, workload is increased to ensure that heart rate maintains at a stable level between 110 and 140 beats/min during the 5th and 6th-min of cycling test. Based on gender, workload, weight and heart rate of minute 5 and 6, maximal oxygen consumption is estimated. Heart rate will be monitored continuously during testing by a Polar heart rate monitor (Polar V800, Kempele, Finland). Patients using betablocker medication follow an adjusted test in which the workload is steadily increased similar to the standard test until a Borg Rating of Perceived Exertion score of at least 12 is reached.

Handgrip strength

Muscle strength will be measured by handgrip strength of the dominant hand. This will be assessed with a hydraulic, analogue hand dynamometer (Jamar, Jackson, Michigan, USA) adjusted to the hand size of every patient. The patient is seated in a chair with the elbow flexed in a 90 degree angle position. Arm support by the chair is not allowed. Three measurements will be performed with approximately 30 s rest between measurements. The maximum strength effort in kilograms will be used for analysis.

Quality of life and cardiac anxiety

Quality of life will be measured using the HeartQoL.18 This is a health-related quality of life questionnaire and has been found to be both valid and reliable in patients referred to CR. Cardiac anxiety/personality will be measured using the Cardiac Anxiety Questionnaire.19 Online questionnaires will be sent to participants by email and take approximately 20 min to complete.

Blood samples

A venous blood sample (obtained by venepuncture) is collected to assess low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, glucose and haemoglobin at baseline and at 18 weeks of follow-up.

Data management and accessibility

All data will be stored in the Digital Research Environment (www.andrea-consortium.org), an online and easy-to-use cloud platform which allows users across the globe to merge, analyse, store, share, archive and publish data in a safe and compliant way (ie, security, information and communications technology (ICT)infrastructure, audit trail, general data protection regulation (GDPR) compliant). Standard software packages are available for data handling and statistical analyses (eg, SPSS, R, SAS). In line with the Open Science initiative and the FAIR principles (Findable, Accessible, Interoperable and Reusable), data from the Cardiac RehApp study will be available for reuse on reasonable request via the corresponding author.

Sample size

Sample size was calculated using G*power (V.3.1.9.4, Kiel University, Germany). A power calculation was performed with differences in PA volumes (expressed in min/week) as the primary outcome measure. The sample size (n) was calculated with a power of 80% (1−β=0.80) and a significance level of 5% (α=0.05). We used data from a previously published study as a reference that looked at changes in PA before and after CR using objective measurements.12 They found a change in PA volume from pre-CR to post-CR of 0.65%±2.21% of total daily wearing time during awake hours (852 min). This equals an increase of 7 min/day. According to these data, during CR an average increase of 49 min/week of moderate to vigorous PA was observed. In this study, the greatest difference is expected between the CR group (usual care) and the +CR+ group (home-based during CR and post-CR). Several large-scale epidemiology studies have been performed that examined the dose–response relationship between PA and CVD and premature mortality.16–19 Small increases in exercise volumes as little as 10 min/day of brisk walking is associated with 33% risk reduction for all-cause mortality, whereas the greatest risk reductions occurs at levels of 150 min/week of moderate-intensity activity and is therefore recommended globally.20–23 Based on these previously reported risk reductions and recommendations, we believe an average difference of 20 min of moderate to vigorous PA per day in the +CR+ group compared with the control group is a reasonable effect and is likely to have significant clinical relevance. Using the average standard deviation (23 min/day) measured in the previously mentioned study and the expected maximum difference between the four groups, an effect size of 0.33 was calculated. This resulted in a total number of participants in of 104. Taking a dropout of 20% into consideration, we will include n=33 participants in each group. With 33 participants in each group, the total calculated sample size is 132.

Statistical analysis

Statistical analyses will be performed using SPSS V.25.0 statistical software (IBM, Chicago, Illinois, USA). Collected data will be checked for completeness and normality of distribution (checked visually and using the Kolmogorov-Smirnov test). All normally distributed data will be presented as means±SD or as median (IQR) when data are not normally distributed. Statistical significance will be set at p<0.05.

Intention-to-treat analysis will be used, based on the group they were initially (and randomly) allocated to, regardless of whether or not they dropped out or fully adhered to the treatment. Summary descriptive statistics, including demographics, will be generated for baseline characteristics. Depending on distribution, baseline characteristics between the two groups will be compared using an independent student t-test or Mann-Whitney U test. Changes in time spent on moderate to vigorous PA measured by the ActivPAL will be used as primary study outcome. We will conduct linear mixed models to simultaneously investigate the effects of the CR interventions and how they change over time, and to investigate the effects of the CR intervention at each time point. To do so, we will use the interventions, time points and the interaction between the intervention and time points as categorical factors. When necessary, a random intercept will be added to the model. We will use a similar statistical approach to analyse differences in total sitting time, physical fitness and CV risk scores. Adherence to the centre-based CR programme and compliance to the Virtual Training programme will be reported as descriptive statistics.