Telerehab III is a multi-center, prospective, randomized, controlled clinical trial recruiting one hundred and forty stable coronary artery disease (CAD) and/or chronic heart failure (CHF) patients (Fig. 1). Patients are randomized in equal proportions to one of two groups: internet-based telerehabilitation in addition to center-based rehabilitation (intervention group) or center-based rehabilitation alone (control group). Patients are enrolled after completion of the first six weeks of their phase II center-based rehabilitation program. They are followed for a minimum of 6 months and a maximum of 25 months.

Patients are recruited from the Cardiology Departments of three Belgian hospitals i.e. Jessa Hospital (Hasselt), Ziekenhuis Oost-Limburg (Genk) and St. Franciscus Hospital (Heusden-Zolder). The Jessa Hospital acts as the coordinating center for the trial. Each participating site is responsible for the recruitment and scheduled follow-up visits of patients; but also for contingency patient management. Each site recruits at least ten patients.

The study is conducted in accordance with the principles stated in the Declaration of Helsinki (reviewed version of 2008), local and national regulations. Written informed consent is obtained from all patients prior to study enrollment. The study is approved by the appropriate ethics committee prior to study enrollment, (Jessa Ethics Committee; reference number: B243201216043).

The study adheres to the relevant standards of reporting. A completed CONSORT checklist can be found in Table 1. There were no important changes to the methods after trial commencement.

Patients belonging to one of the two cardiac disease categories (ia CAD for which patients were treated conservatively, with a percutaneous coronary intervention or with coronary artery bypass grafting OR ib CHF with reduced EF (NYHA I, II and III) OR ic CHF with preserved EF (NYHA I, II and III)) and who had signed the informed consent form; are eligible to participate. All patients were on optimal medical treatment and stable for >4 weeks. In addition, eligible patients are at least 18 years and maximally 80 years old. They must have a personal computer with internet connection.

The main exclusion criteria are: the presence of a pre-existing non-cardiovascular condition (orthopedic and/or neurological), limiting the patient’s ability to actively engage in exercise training; the presence of terminal disease, dementia and cognitive impairment that unables the patient to use the telerehabilitation equipment or appear to follow-up visits. The complete list of inclusion and exclusion criteria is provided in Table 2.

The sample size calculation is based on a 20 % effect size of VO2 peak , which is comparable to the effect reported by Frederix et al. in their Telereab II study [9]. In order to attain a minimal power of 95 %, at an alpha error probability < 0,05; 140 patients should be recruited when taking into account a dropout rate of 30 % during follow-up.

Patients are assigned to one of two treatment arms by a central computerized randomization system. Block randomization is used to ascertain equal distribution of patients in the intervention and control group in the different recruiting hospitals. In order to achieve a balance of relevant patient characteristics in both study arms, it will be assessed whether patients are matched for age, gender, cardiac disease category and cardiovascular risk factor profile. When intervention and control patients are not matched for these characteristics, a second randomization process will be done to ascertain matching. Investigators are unaware of the randomization sequence.

At entry of study a complete medical history, clinical assessment (including measurement of body mass index, waist circumference, blood pressure and heart rate) and treatment scheme are collected. A transthoracic echocardiography (TTE) evaluating LV systolic function (using Simpson’s method and/or eye balling), LV diastolic function (E/A ratio, DT, IVRT and pulmonary venous flow curves) and presence/absence of increased left atrial filling pressures (average E/E’) is planned, when no recent TTE (performed < 6 months earlier) is available. Every patient performs a maximal cardiopulmonary exercise test (CPET) with breath-by-breath gas exchange analysis. The criteria for defining maximal CPET are an achieved heart rate > 85 % of the maximal predicted heart rate, an achieved Respiratory Exchange Ratio (RER) > 1,1, and/or achieving a plateau on the VO2 curve. During CPET, we will record RER, resting and maximal heart rate, resting and maximal systolic and diastolic blood pressure, resting and maximal rate pressure product, VO2 peak, maximal work load, ventilatory anaerobic threshold, respiratory compensation point and the oxygen uptake efficiency slope. We will use the recommendations provided by Wasserman et al. to predict VO2 peak and to calculate % of predicted VO2 peak [10]. Fasting blood samples are taken, to determine blood glucose, HbA1c, CRP level and lipid profile. Patients are asked to complete a quality of life questionnaire (HeartQol), a questionnaire to assess self-reported physical activities (IPAQ) and the EQ-5D questionnaire. After randomization, study visits were scheduled after 6 weeks as well as at the end of study period. During these visits, clinical assessment, treatment scheme collection and maximal CPET are performed. Patients are again asked to complete the HeartQol, IPAQ and EQ-5D questionnaires. Blood sampling is only repeated after study completion (Fig. 1).

Patients in the intervention group are provided with an internet-based telerehabilitation program in addition to conventional center-based CR. The telerehabilitation program is composed of physical activity telemonitoring (Yorbody accelerometer) in addition to dietary, smoking cessation and activity telecoaching.

Patients in the control group follow the conventional center-based CR program; including 45 pluridisciplinary rehabilitation sessions focusing on healthy diet, psychosocial wellbeing, behavioural change, risk factor modification and exercise training. The exercise training sessions are scheduled 2 to 3 times/week; with an average session duration of 45 min. Training intensity is progressively increased from the ventilatory anaerobic threshold to the respiratory compensation point. Main exercise modalities include walking/running and cycling.

These patients are instructed to wear the accelerometer three times; at study start, after 6 weeks and at the end of study period for observation purposes only. The sensors are taped at the hospital using black tape, making it impossible for the patient to see the registered physical activity data. Data uploading is performed by study nurses of the respective hospitals, patients cannot consult the webpage with uploaded data. They do not receive physical activity, smoking cessation or dietary telecoaching by email and/or SMS.

The primary endpoint is peak oxygen consumption (VO2 peak). The first secondary endpoint is daily physical activity, defined as the total number of daily low intensity and high intensity steps.

Other secondary endpoints include:

Outcome assessors were blinded to treatment allocation.

A Clinical Endpoint Committee (CEC), composed of three specialists in internal medicine (with at least two of them cardiologists), will classify all rehospitalizations. This classification will be based on the completion of templates defining the criteria and definitions for cardiovascular and/or non-cardiovascular rehospitalizations.

The statistical analysis will be performed according to the Intention-to-treat principle. For continuous data, the Shapiro-Wilk test will investigate whether normal distribution is present. When data are not normally distributed, the Mann–Whitney U-test will be used for the comparison between groups; and the Wilcoxon Signed Rank test will be used for the comparison within groups. When data are normally distributed the One Way ANOVA repeated measures test will be used for both between and within group analysis. Kaplan-Meier plots and log-rank tests will be used to compare censored time-to-event data; for the time to first cardiovascular rehospitalization and time to first rehospitalization for any reason. The statistical software package SPSS will be used for analysis. P-values <0,05 will be considered statistically significant.