CABGpreHAB- Home-based Multimodal Prehabilitation (CABGpreHAB) for Elective Patients Awaiting CABG-surgery - a Feasibility Study Protocol
Phase: NA
Conditions: Ischaemic Heart Disease, Prehabilitation, Coronary Artery Bypass, Feasibility Studies, Multimodal Intervention, Adult
Sponsor: Rigshospitalet, Denmark

Protocol: CABGpreHAB 
 
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CABGpreHAB 
Homebased multimodal prehabilitation (CABGpreHAB) for 
elective patients awaiting CABG surgery – a feasibility study 
protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Sponsor  
Department of Cardiothoracic Surgery, The Heart Centre 
Copenhagen University Hospital, Rigshospitalet 
Inge Lehmanns Vej 5, 
DK- 2100 Copenhagen O, Denmark 
 
 
Principle investigator 
Ida Elisabeth Højskov, RN, MScN, PhD  
Department of Cardiology, The Heart Centre, Rigshospitalet 
Copenhagen University Hospital, Rigshospitalet 
Inge Lehmanns Vej 5 
DK - 2100 Copenhagen O, Denmark 
 
Project leader 
Dorte Bæk Olsen, RN, MCN, PhD student 
Department of Cardiothoracic Surgery, The Heart Centre 
Copenhagen University Hospital, Rigshospitalet 
Inge Lehmanns Vej 5 
DK- 2100 Copenhagen O, Denmark 
 
  
 
 
 
 
 
 
 
 
 
 

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Table of content 
List of abbreviations and definitions ............................................................................................................. 5 
1. Introduction and background .................................................................................................................... 6 
1.1 Introduction............................................................................................................................................ 6 
1.2 Background ........................................................................................................................................... 6 
1.2.1 Waiting for elective CABG surgery ............................................................................................. 7 
1.2.2 Recommendation and guidelines ............................................................................................... 8 
1.2.3 Prehabilitation in patients with IHD awaiting elective CABG surgery. .................................. 8 
2. Study aim and objectives ........................................................................................................................ 10 
2.1 Primary objective ................................................................................................................................ 10 
2.2 Secondary objective: ......................................................................................................................... 11 
3. Method ....................................................................................................................................................... 11 
3.1 Study design ....................................................................................................................................... 11 
3.2 Inclusion and screening procedure ................................................................................................. 11 
3.3 Randomization .................................................................................................................................... 12 
3.4 Blinding ................................................................................................................................................ 12 
3.5 Participant timeline ............................................................................................................................. 12 
3.6 Sample size and power ..................................................................................................................... 13 
4. Selection and allocation of participants ................................................................................................. 13 
4.1 Inclusion criteria .................................................................................................................................. 14 
4.2 Exclusion criteria ................................................................................................................................ 14 
4.3 Participant discontinuation and withdrawal .................................................................................... 14 
4.3.1 Discontinuation and withdrawal at the choice of the participant .......................................... 14 
4.3.2 Discontinuation and withdrawal at the choice of the investigator ........................................ 14 
5. Study site and personnel ......................................................................................................................... 15 
5.1 Study site and setting ........................................................................................................................ 15 
5.2 Study personnel .................................................................................................................................. 15 
6. Study interventions ................................................................................................................................... 15 
6.1 Control intervention/Usual care ........................................................................................................ 15 
6.2 Multimodal prehabilitation interventions (CABGpreHAB) ............................................................ 16 
6.2.1 Exercise intervention .................................................................................................................. 16 
6.2.2 Nutritional intervention ............................................................................................................... 17 
6.2.3 Psycho-educative intervention .................................................................................................. 17 

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6.2.4 Smoking cessation intervention ................................................................................................ 18 
6.2.5 Alcohol cessation intervention .................................................................................................. 18 
7. Study outcome measures ....................................................................................................................... 19 
7.1 Primary outcome ................................................................................................................................ 19 
7.2 Secondary outcome ........................................................................................................................... 20 
8. Data collection .......................................................................................................................................... 24 
8.1 Data from questionnaires .................................................................................................................. 24 
8.2 Data from patient records ................................................................................................................. 25 
8.3 Data from Danish registries .............................................................................................................. 25 
8.4 Biological material .............................................................................................................................. 25 
9. Analysis ...................................................................................................................................................... 26 
9.1 Statistical methods ............................................................................................................................. 26 
10. Ethics ....................................................................................................................................................... 26 
10.1 Ethical considerations ..................................................................................................................... 26 
10.2 Adverse events and reactions ........................................................................................................ 27 
10.2.1 Definitions .................................................................................................................................. 27 
10.2.2 Risk and safety issues in the current trial ............................................................................. 27 
10.2.3 Assessment of adverse advents ............................................................................................ 27 
10.2.4 Severity of adverse events ...................................................................................................... 28 
10.3 Risks and benefits ............................................................................................................................ 28 
10.3.1 Risk and timing of surgery ........................................................................................................... 28 
10.4 Ensuring integrity and privacy of the participant ......................................................................... 29 
10.5 Oral information and informed consent ........................................................................................ 29 
11. Legal and organizational aspects ........................................................................................................ 29 
11.1 Quality control and quality assurance ........................................................................................... 29 
11.2 Economy............................................................................................................................................ 29 
11.3 Insurance ........................................................................................................................................... 30 
11.4 Plan for publication, authorship, and dissemination ................................................................... 30 
11.5 Trial timeline ...................................................................................................................................... 30 
12. Organization ............................................................................................................................................ 31 
13. References .............................................................................................................................................. 32 
 
 
 

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List of abbreviations and definitions 
AF 
 
Atrial fibrillation 
AMI 
 
Acute myocardial infarct 
AE: 
  
Adverse event 
BMI: 
 
Body Mass Index 
BIA:  
 
Bio electrical Impedance Analysis 
CABG:  
 
Coronary Artery Bypass Grafting 
CAD: 
 
Coronar artery disease 
CR: 
 
Cardiac rehabilitation 
DAOH30 
 
Days alive out of hospital30 
HRQoL: 
 
Health related quality of life 
ICU: 
 
Intensive care unit 
ICU-LOS: 
 
Intensive care unit – length of stay 
IHD: 
 
Ischemic heart disease 
LOS: 
 
Length of stay 
MDT: 
 
Multi-disciplinary team conference 
MI 
 
Myocardial infarct 
NRT: 
 
Nicotine replacement therapy 
NYHA: 
 
The New York Heart Association 
PAM13 
 
Patient activation measure 
PCI: 
 
Percutaneous coronary intervention 
PHQ-4 
 
Patient Health Questionnaire for depression and anxiety 
QoL: 
 
Quality of life 
RCT: 
 
Randomized clinical trial 
SD: 
 
Standard deviation 
SOC-13 
 
Sense of coherence -13 
STAI 
 
The State-Trait Anxiety Inventory 
UC: 
 
Usual care 
6MWT:  
       
6-minute Walk Test 
 

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1. Introduction and background 
1.1 Introduction 
Advanced age, frailty, comorbidity and physical inactivity are often present in patients with ischemic heart 
disease (IHD) awaiting coronary artery bypass graft surgery (CABG) surgery.1 These characteristics, as well as 
the physiological impact of having surgery are significant homeostatic disturbances where patients 
postoperatively suffer from physical symptoms and a lack of a return to independence.2,3 Cardiac surgery 
invariably induces varying degrees of physiological stress, impacting multiple organ systems, and imposes 
psychological burden.4 As increasing age, patient complexity and comorbid burden grow more common in 
patients undergoing cardiac surgery, innovative strategies are required to alleviate the risk of adverse 
outcomes.5 Strategies to improve outcomes from surgery and accelerate return to baseline levels have 
traditionally focused on the intra-and postoperative period, nevertheless the waiting period before surgery 
might offer an opportunity for improving the safety and outcome of the surgical intervention and improve 
patients’ motivation in postoperative rehabilitation and recovery time.6,7 
1.2 Background 
IHD constitutes a significant cause of mortality and morbidity globally, and accounts for over four million 
deaths annually in Europe, placing a great strain on healthcare resources.8,9  In Denmark, cardiovascular 
diseases account for the death of one in five individuals, representing the second leading cause of mortality 
in the country.10,11  Specifically, IHD was the predominant cardiovascular disease leading to death among 
Danes in 2021, with an estimated 12,000 deaths attributed to cardiovascular diseases each year.12  The 
prevalence of IHD escalates with advancing age and is notably higher in men compared to women, including 
within the elderly population.  In Denmark, approximately 163,000 individuals are currently living with IHD, 
and approximately 12,000 new cases are diagnosed annually.13 The economic burden of IHD is substantial, 
with annual costs for treatment, care, medication, and lost productivity estimated at approximately 5.5 
billion DKK. 14,15 IHD results from atherosclerosis in the coronary arteries, reducing blood flow to the heart 
muscle. This condition, also known as coronary artery disease (CAD), causes arterial narrowing, which can 
lead to angina, blood clots, and myocardial infarction (AMI), commonly known as a heart attack.16 Diabetes, 
hypertension, and dyslipidemia are known to be major cardiovascular risk factors influenced by unhealthy 
lifestyle behaviors such as smoking, alcohol consumption, physical inactivity, and a diet high in calories and 
trans-fat acid. Smoking known as one of the main risk factors for developing IHD causes every year 3000 new 
cases of IHD in Denmark.17 An unhealthy lifestyle plays a fundamental role in the development of 
cardiovascular disease (CVD), requiring emphasis and attention,18 while impacting both health outcomes and 
quality of life. Importantly, these risk factors are modifiable, offering substantial potential for reducing CVD 
risk through both primary and secondary prevention strategies.9 Standard treatment in multivessel disease 

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in patients with IHD is revascularization by coronary artery bypass graft (CABG) surgery, a well-recognized, 
treatment to relieve symptoms of angina, improve exercise capacity, quality of life and survival.19,20 In 2021 
a total of 1195 isolated CABG-procedures were performed at the four heart surgery centers in Denmark.21 
Out of these were 580 carried out at The Department of Cardiothoracic Surgery at Rigshospitalet, either as 
an elective or acute procedure.22 CABG is acknowledged as “state of the art,”23,24  and is one of the most 
frequently performed cardiac surgeries in the Western world associated with better long-term survival 
compared to PCI in most regions in the world.25 Despite advances in surgical techniques, anesthesiology 
and perioperative care4 postoperative complications, including infections, hemorrhage, arrhythmias, graft 
failure, atrial fibrillation, pneumonia, renal injury, and cerebrovascular events, are associated with an 
elevated risk of both early and late mortality and all-cause rehospitalization, particularly within 90 days of 
CABG.26 
1.2.1 Waiting for elective CABG surgery 
Most patients scheduled for elective CABG surgery wait at home and undergo little or no physical training or 
other interventions in the lead up to their operation. Evidence shows that patients deteriorate functionally 
and psychologically during this period prior to surgery.1,27 Furthermore, studies show that the time spent 
waiting for cardiac surgery is a period of great uncertainty for the patient. There appears to be heightened 
anxiety regarding physical activity, mainly because of their current cardiac conditions or diagnosis.27,28,29 
Subsequent physical inactivity characterized by sedentary behavior and lifestyle may add to the underlying 
IHD and this has been recognized as one of the coronary artery disease’s major risk factors.30 In line with this 
results from the Heart Centre's cross-sectional study conducted in the fall of 2018 and 2019, involving 130 
hospitalized cardiac surgery patients, reported low activity level during the four weeks preceding their 
surgery indicating sedentary lifestyle in the weeks leading up to their cardiac surgery.31 Studies show that a 
decrease in physical activity quickly leads to a decline in physical fitness and reduces the physiological 
capacity to withstand the side effects of surgery.27,32 Studies show that ischemic heart patients awaiting 
surgery often have difficulty maintaining a normal level of physical activity, which in turn leads to reduced 
oxygen uptake and loss of muscle mass.30 Symptoms such as fatigue, shortness of breath, and fear of angina 
pain can prevent the patient from being physically active.28,29 Additionally, anxiety and depression can 
contribute to reduced motivation to be physically active during the waiting period before surgery.28 
Moreover, resent research revealed that the prevalence of sarcopenia in older patients at cardiac 
rehabilitation (CR) after cardiac procedure is high (35 %), and remains high at follow-up (23%) and indicates 
correlations with poor functional capacity.33 Ensuring that patients are in optimal nutritional health before 
undergoing CABG surgery is crucial, as it is an important driver for clinical outcomes in this population. 
Malnutrition, defined as an unintended nutritional intake imbalance (not necessarily a decreased intake), 

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is evident in 20 % of patients before cardiac surgery associated with increased morbidity and mortality.34,35 
Malnutrition before surgery has been associated with longer length of stay (LOS) in the intensive care unit 
(ICU) and higher rates of postoperative cardiovascular and infectious complications.36,37 Further smoking 
and alcohol overconsumption are well known risk factors for a complicated recovery after CABG-surgery 
including delayed wound healing, pulmonary complications, and mortality.38 Moreover preoperative 
alcohol abuse and misuse are likely causes of subclinical myocardial dysfunction, immunosuppression, and 
decreased hemostasis – increasing the risk of hemodynamic instability, infection, and bleeding.39,40 
 
1.2.2 Recommendation and guidelines 
The adoption of routine preoperative optimization strategies for patients awaiting CABG surgery has so far 
been limited although the Health Authority's "Recommendations for Cross-Sectional Pathways for People 
with Heart Disease," suggest that the multi-diciplinary team (MDT) conference's conclusion should also 
include a plan for preoperative preparation to improve postoperative outcomes and increase rehabilitation 
potential.41 In Denmark, patients have historically been waiting weeks for heart surgery but it fluctuates.  
Patients are called for heart surgery approximately two to four weeks before, where they either remain 
hospitalized or are discharged home during the waiting period. The patient receives written informational 
material about the process before and after CABG  surgery. For patients who are fully examined and referred 
for CABG surgery, there will be an intermediate period. In this period  it is recommended that  the patient is 
prepared for the procedure and that the rehabilitation potential is strengthened through physical activity, 
thereby reducing the loss of function before subsequent rehabilitation. In addition to  optimization of 
medication and chronic conditions, patients should be offered, smoking and alcohol cessation, nutritional 
support, and physical training according to individual need.41 
Evidence suggest smoking cessation at least four weeks before CABG surgery reduces the risk of major 
postoperative pulmonary complications such as reintubation, atelectasis and pneumonia.42 The 
reccomendations by The Danish Health authority is smoking cessation six weeks before surgery.43 Similar to 
smoking cessation, abstinence from alcohol is not treated as a prerequisite for surgery, but reccomendations 
from the Danish Health Authoriry recommend zero alcohol intake four weeks before surgery.44 The European 
Society for Clinical Nutrition and Metabolism guidelines recommend an increased intake of protein before 
surgery to reduce the physiological stress response after surgery.45  
1.2.3 Prehabilitation in patients with IHD awaiting elective CABG surgery. 
Prehabilitation is a newly introduced term that reflects a proactive process of enhancing an individual’s 
functional capacity between diagnosis and scheduled surgery, intending to improve the patient’s capacity to 
withstand the upcoming physiologic stress of surgery and thus avoid complications.46 This period of awaiting 

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surgery is proposed as  a “window of opportunity” to address poor nutritional status, low physical fitness, 
and high emotional distress.47,48 The role of multimodal prehabilitation combining exercise training, 
nutritional optimization, and psychological support, in patients with IHD awaiting CABG surgery is sparse49 
and unknown in a Danish setting. We conducted a scoping review50 of prehabilitation in elective CABG 
surgery patients in accordance with JBI methodology for scoping reviews,51,52 in May 2023. We updated the 
systematic literature search in Medline (PubMed), Embase (Ovid) and Cochrane Central in February 2024 to 
identify new studies on the topic. This scoping review50 examined prehabilitation interventions to optimize 
outcomes after elective CABG surgery and found that available evidence is mostly based on small studies 
with high heterogeneity. Prehabilitation before CABG-surgery has been described as a combination of 
exercise training, education, and social support affecting patients` physical and psychological readiness for 
surgery intended to reduce postoperative complications and LOS.6,53,54 To ensure that patients undergoing 
elective CABG surgery benefit from prehabilitation, there is a need for methodologically rigorous clinical trials 
and comprehensive knowledge synthesis. These efforts are necessary to identify optimal strategies for 
patient selection, intervention design, adherence, and the duration of interventions.50 Additionally, existing 
evidence indicates that prehabilitation programs should be tailored and centered around individual patient 
needs.55 Recently a meta-analysis examining the effects of exercise-based prehabilitation in cardiac surgery 
patients on various perioperative outcomes, as compared to standard care, demonstrated significantly 
improved post-surgery six-minute walking distance, reduced LOS, and a decreased risk of postoperative atrial 
fibrillation (AF) in patients aged 65 years or younger.7 Furthermore a systematic review confirmed 
improvement in functional capacity and declines in in postoperative complications and LOS.56 
This support prehabilitation as integrated into cardiac surgical planning57  towards optimizing patients before 
surgery and potentially enhance surgical outcomes. However, it also concludes that the ideal prehabilitation 
regimen remains uncertain, particularly in terms of the significance of dietary modifications and 
psychological preparations for surgery, the benefits of which are not yet fully understood in cardiac surgical 
patients.57 Nevertheless, a formalized prehabilitation program focusing on prehabilitation for cardiac surgery 
patients has not yet been established in Denmark. We propose that patients awaiting elective CABG surgery 
who receive a home-based multimodal prehabilitation intervention, in addition to usual care (UC), will show 
improvements in physical activity, functional capacity, mental health, and quality of life postoperatively. 
These improvements may also positively impact health behavior, health outcomes, length of hospital stay, 
and days alive out of the hospital after surgery. Additionally, as far as we know no previous studies have 
investigated a home-based multimodal prehabilitation intervention program within this patient population 
in Denmark, while recent findings in a scoping review50 provides a comprehensive summary of strategies that 
will be applied when developing a prehabilitation program for patients awaiting elective CABG surgery for 

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optimizing physical capacity, lifestyle behaviors, mental health, and nutritional status in preparation prior to 
CABG surgery.50 Before a larger randomized controlled trial (RCT) can be conducted, a feasibility study is 
required to determine if a larger trial is possible, and if so, outline the optimal design features.58 It can be 
described as complex interventions according to the UK Medical Research Council, why conducting a 
feasibility study as part of the process from developing to implementation is recommended.59 
2. Study aim and objectives   
This CABGpreHAB feasibility study is conducted to evaluate the feasibility of delivering a homebased 
multimodal prehabilitation intervention for patients awaiting elective CABG surgery with the purpose to 
optimize a subsequent full-scale RCT: 
2.1 Primary objective 
The primary objective of this feasibility study is to determine if it is feasible for patients awaiting elective 
CABG surgery to participate in a preoperative homebased multimodal prehabilitation intervention. We will 
evaluate this through completion of the following objectives: 
- 
Assess the proportion of eligible patients that are recruited into the study. 
- 
Assess the suitability of inclusion and exclusion criteria by examining recruitment data.  
- 
Explore reasons for non-consent to study participation. 
- 
Assess the acceptability of the study to patients by measuring recruitment and retention to the 
study and thorough qualitative interview responses.  
- 
Assess the acceptability of the intervention through qualitative interviews and retention rates 
during the study. 
- 
Assess adherence to and completion of the intervention (i.e.  do participants adhere and work 
through all components of the intervention) and explore engagement and satisfaction with the 
interventions by qualitative interviews. 
- 
Assess the proportion of patients lost to follow-up  after study entry. 
- 
Assess safety of the interventions.  
- 
Explore the appropriateness of outcome measures, completion rates and assess response to 
questionnaires through qualitative interviews.  
- 
Evaluate the logistics of delivering a home-based tele-exercise training intervention through 
qualitative interview responses from both health care professionals and patients. 
- 
Determine the “prehabilitation window” (length of time between MDT-conference and CABG 
surgery)  

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2.2 Secondary objective: 
The secondary objectives will evaluate if the multimodal prehabilitation intervention has an impact on 
preoperative and postoperative outcomes. For this we will collect data on study outcomes to assess levels, 
variation, and changes over time, which can inform sample size for the future RCT, as shown in Table 1. 
section 7.2 
3. Method 
3.1 Study design 
The CABGpreHAB feasibility study is designed as a randomized pilot study, aiming to assess the feasibility of 
a multimodal prehabilitation intervention plus usual care versus usual care alone in patients awaiting elective 
CABG surgery. It is an investigator-initiated study designed as an open-label, single-center randomized 
controlled feasibility study (allocation ratio 1:1) with blinded outcome assessment, designed to assess the 
method proposed for use in a larger RCT. This protocol follows guidance from Standard Protocol Items: 
Recommendations for interventional Trials (SPIRIT).60 The CABGpreHAB study will be registered at 
www.ClinicalTrials.gov before initiation. 
3.2 Inclusion and screening procedure 
Patients referred to elective CABG surgery who are deemed eligible due to inclusion criteria will be identified 
and assessed for eligibility by the responsible surgeon after the MDT-conference as shown in Figure 1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3.3 Randomization 
Following baseline assessment, randomization will occur in a 1:1 ratio, stratified by age, gender (men, 
women), and EuroSCORE (indicative of disease severity), assigning participants either to the intervention 
group or to usual care. Randomization is completed using the web-based tool Randomizer for Clinical Trials. 
3.4 Blinding 
Due to the nature and conditions of prehabilitation, the interventions are open, making it impossible to blind 
the interventions to the staff and patients.61 However, all physical testing, data collection, and administration 
will be conducted by blinded staff. Statistical analysis of outcomes and the conclusions derived from these 
analyses will also be performed in a blinded manner. The study results will be analyzed by an independent 
statistician, and the research group will interpret the results. The conclusions will be prepared in two versions 
before the allocation code is broken, with each version assuming alternately that one arm is the intervention: 
one version will assume that arm A is the intervention, and the other will assume that arm B is the 
intervention. 
3.5 Participant timeline 
After the MDT conference eligible patients identified from the elective waiting list for CABG-surgery are 
invited to participate. When they have contended, they will be allocated to either CABGpreHAB plus usual 
care or usual care alone. The intervention will be launched immediately after inclusion in the study. At 
baseline a face-to-face introduction and counselling will take place at the preoperative clinic at the 
Department of Cardiothoracic surgery Rigshospitalet. There will be assessment at baseline, the day before 
surgery (ending of the intervention period) and on day 30 post surgery. All study participants will wear the 
accelerometer from the screening phase until the day preceding the procedure, and again postoperatively 
until the day of discharge and for 30 days thereafter as illustrated in Figure 2.  
 
 
 
 
 
 
 
Figure 2. Graphical illustration of the study design 

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3.6 Sample size and power 
As the primary aim of this study is to evaluate feasibility, there is no formal requirement for a formal power 
calculation.62 Sample sizes between 24 and 50 have been recommended.63,64 A sample size of 25 patients in 
each group was chosen as it seems reasonable to provide outcome data in a small sample, and at the same 
time a sample size large enough to investigate the additional aspects that are being assessed for feasibility65 
informing a future power calculation for a full-scale RCT. 
4. Selection and allocation of participants 
Following the MDT conference in the department of Heart and Lung Surgery, Rigshospitalet the responsible 
surgeon screen for eligibility by comparing patients’ referral against the inclusion and exclusion criteria as 
described in this protocol section 4.1. If the patient is deemed eligible after screening, they will receive an 
invitation in e-Boks  to be contacted for a brief information about the  study.  If they accept this invitation, 
the patient will be contacted by telephone by a responsible clinician in the project, and if the patient is 
interested to hear more, written information material about the study will be send by e-Boks or regular post. 
The patient will be informed that participating is voluntary, that they have the right to bring a bystander for 
the oral information, which will take place when they meet for the planned visit in the pre-clinic some days 
later. If patients haven’t got the invitation about information in E-boks the responsible surgeon will introduce 
the study for eligible patients and present patients with the written information at the meeting in the pre-
clinic . The oral information will be given with no external interruptions and will be given in a language easily 
understood without technical or value laden terms. The patient will receive a full explanation of the study 
design and study procedures, and information about usual care. This information interview is performed by 
the principal investigator or in her absence by a designated delegate. Consent to participation is given on the 
basis of written and oral information. Prior to consent, it must be ensured that a potential participant has 
been given sufficient time to consider his or her participation and minimum 24 hours. However, potential 
participants can sign earlier if they wish. An informed consent form must be signed and dated by the 
participant prior to participation in the trial. A copy of the form is provided to the participant. The principal 
investigator and her designated delegates can receive the signed consent form. When the written informed 
consent is received, the study specific procedures such as test, randomization and other study related 
procedures will take place. 
Patients will be eligible if they comply with the inclusion criteria in line with previously used criteria.66,67 
Exclusion criteria are listed below. 
 

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4.1 Inclusion criteria 
• 
Planned to have elective isolated first-time CABG surgery. 
• 
18 years or older 
• 
Two weeks or more prior to surgery 
• 
Speaks and understands Danish. 
• 
Gives written informed consent. 
4.2 Exclusion criteria 
• 
Patient with unstable angina pectoris and/ or MI during the last two weeks.  
• 
Left main stem stenosis >50%  
• 
Left ventricular ejection fraction < 35% 
• 
Significant ventricular arrhythmia 
• 
Orthopedic or neurologic preconditions precluding exercise training.  
• 
Inability to attend the prehabilitation program due to physical limitations. 
• 
Patients who have cognitive deficits that would disqualify prehabilitation.   
• 
Severe heart failure, NYHA Class IV 
• 
Lack of capacity to consent 
 
4.3 Participant discontinuation and withdrawal 
4.3.1 Discontinuation and withdrawal at the choice of the participant 
Participants in the study can freely withdraw their informed consent at any time and be treated according to 
the department’s standard procedures. Patients will be excluded from the study if they withdraw their 
consent and will be informed that withdrawal from the study will not affect their future treatment. If possible, 
the reason for withdrawal will be obtained and reported. The patient is not obligated to give reasons for 
withdrawal. Patients who leave the study will be asked for permission to continue to collect data and to use 
already collected data. If the patient gives permission, he/she will be included in the final analysis. Only if the 
patient refuses the use of already collected data, all data relating to him/her, will be destroyed.  
4.3.2 Discontinuation and withdrawal at the choice of the investigator 
The project team reserves the authority to halt the participation of any individual involved in the study, 
primarily in response to adverse events and concerns regarding safety. Additionally, the principal investigator 
retains the right to conclude the study. Grounds for such termination may encompass inadequate adherence 
to the study’s protocol, challenges in participant recruitment, deviations from the established timeline, and 
administrative discrepancies. 

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5. Study site and personnel 
5.1 Study site and setting 
The CABGpreHAB feasibility study will be carried out in The Department of Cardiothoracic Surgery at The 
Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen.  
5.2 Study personnel  
In the CABGpreHab study, the interventions are administered by trained specialist nurses specializing in heart 
surgery and specialized physiotherapists. To execute the interventions effectively, the nursing staff will 
undergo skills enhancement through training courses and supervised practice, particularly given the nature 
of the psychosocial interventions involved. The physical exercise program is initiated by physiotherapists with 
specific expertise in exercise training for patients awaiting CABG surgery. The principal investigator is Ida 
Elisabeth Højskov, Sune Damgaard is primary responsible physician/surgeon and Dorte Bæk Olsen is project 
leader.  
6. Study interventions 
All included patients will receive standardized surgical processes and perioperative care under existing 
protocols for preoperative patient education.23,68  
6.1 Control intervention/Usual care  
Participants assigned to the control group will receive usual care including standard information about CABG 
surgery, pre- and postoperative care, and postoperative physical activity advise.68 Patients are informed 
about date of surgery along with information in secure mailbox (e-Boks) after the MDT conference. The date 
for surgery is tentative, and there will always be some risk of postponed surgery for the elective patient due 
to emergency heart surgery. Patients are either admitted the day before surgery or weeks before in our pre-
ambulatory clinic in the Department of Cardiothoracic Surgery at Rigshospitalet. They receive written 
materials and links to animated videos about preparing for surgery is available for all patients undergoing 
elective CABG surgery.69-71 The day before surgery the patient is informed by their heart surgeon and the last 
assessment and preparation for the surgery takes place in the ward. The patients have also been given 
information about the surgery and the postoperative period during their pre ambulatory visit weeks before 
surgery. This preparation includes counselling with a multi-disciplinary team, including a nurse from the 
department, a physiotherapist, cardiothoracic anesthesiologist, and surgeon. During this preoperative 
counselling session, the nurse assesses nutrition status, as well as smoking and alcohol habits. The nurse also 
invites the patient to talk about the situation of being a heart patient awaiting surgery. Preoperative anxiety 
is assessed with The Apais tool to encouraged patients to talk about uncertainty and further needs for 
information. The nurse also provides information related to postoperative expectations such as the ICU, the 

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operation room, and issues related to the postoperative period in the department, such as pain, arrhythmia, 
pulmonary issues, coughing, early mobilization and so on. Furthermore, if patients are consuming high levels 
of alcohol, we contact the “social care nurse at Rigshospitalet”, who can plan with the patient to be abstinent 
before surgery. This preoperative preparation where patients and significant others are invited to participate 
is a well-established practice in the Department of Cardiothoracic Surgery following protocols and guidelines 
in the field.23,68 
 
6.2 Multimodal prehabilitation interventions (CABGpreHAB) 
Patients randomized to the multimodal prehabilitation programme will besides usual care as described above 
receive preoperative interventions that consists of: 
6.2.1 Exercise intervention 
During the initial assessment patients will be taught how to perform the exercises to complete at home 
during the intervention period. The exercise intervention is supervised by skilled physiotherapists and 
delivered via Infinity Connect app and a webcam72 at Rigshospitalet to a group of approximately 4–8 patients 
who exercise at home and communicate via a tablet. Each session is 60 min, i.e., 40 min of exercise and 20 
min of patient education, three times per week for the prehabilitation period. The exercises used in the 
program are identified and selected amongst exercises used in previous exercise intervention studies and 
involves larger muscle groups with 50/50% exercises for upper and lower extremities, respectively.73 The 
exercises are executed in four sets to achieve peripheral muscle fatigue and secondary 
dyspnea/breathlessness. Each set is carried out in a predefined period of 20 to 40 s with a maximum number 
of repetitions performed, i.e., 8 to 25 repetitions depending on the patients exercise capacity and motivation, 
but with the aim of 12 to 20 repetitions.73,74 In practice the training intensity is determined by using the self-
rated Borg Scale, moderate intensity RPE 11-15, 50-60% VO2peak.74 
The first week serve as a familiarization phase with the purpose to adapt to exercising, adjusting, and 
optimizing load and to avoid musculoskeletal overload injuries. Monitoring physical activity and providing 
motivation through phone calls weekly will be enhanced by incorporating a novel accelerometer system, 
offering activity level feedback (SENS innovation)75 to guide healthcare staff. Participants in the intervention 
will be instructed to perform daily exercise tasks such as brisk walking and sit-stand exercises. Additionally, 
motivational phone calls will be made to participants in the intervention group, while healthcare staff will 
receive feedback on these patients, aiding to guide them in achieving their activity goals. Patients will also 
be asked to complete a diary describing physical activity outside the programmed session, included in a 
patient booklet. All study participants will wear the accelerometer from the screening phase until the day 
preceding the procedure, and again postoperatively until the day of discharge and for 30 days 

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thereafter.76,77The technology platform provided to the patients includes a tablet and an accelerometer 
device to facilitate exercise training sessions and data collection. 
6.2.2 Nutritional intervention 
The aim of the nutritional part of the intervention is avoidance of sub-optimal pre-operative nutritional 
intake. All participants will receive the pre-operative nutritional advice as part of usual standard of care. In 
addition, all participants in the intervention arm will be encouraged to follow these guidelines as part of the 
adherence support. The usual care regarding nutritional advice in the period before CABG surgery include 
weight maintenance, intake of energy and protein rich food items as well as micronutrients with focus on a 
daily intake of B and C vitamins. The patients are advised to plan their meals if the appetite is low to ensure 
a sufficient intake of protein and energy before the surgery which is considered more important in the pre-
operative period than following the general advice regarding consumption of vegetables etc.  Energy and 
protein rich supplements are also suggested for patients with low appetite to promote an energy and protein 
rich diet in the pre-operative period.  Nutritional risk will be assessed at baseline and preoperatively using 
the NRS-2002 total score which is already part of usual care.78 After screening with NRS-2002 patients are 
categorized as being nutritionally at-risk patients (score>3) or nutritionally not at risk (score<3) according to 
the total score obtained. Patients not at risk for malnutrition will be provided with nutritional advice 
according to usual care. In addition to usual care regarding nutrition, not at-risk patients will receive 
encouragement to follow the nutritional advice as part of adherence support throughout the intervention 
period. I addition to usual care at-risk patients will be offered protein and energy rich supplements free of 
charge as well as individualized advice and encouragement as part of adherence support throughout the 
intervention period.  
6.2.3 Psycho-educative intervention  
The intervention seeks to enhance preparedness for CABG surgery through individualized assessment and 
review of psychosocial factors that may influence treatment outcomes and quality of life. Mental health such 
as emotional well-being and stress reduction will serve as primary foci of this psycho-educative intervention 
inspired by Antonovsky’ s salutogenetic theory known as Sense of Coherence (SOC).79 The SOC is composed 
of three key components: comprehensibility, manageability, and meaningfulness. According to Antonovsky, 
a strong SOC enables individuals to view stressors as less threatening and more manageable, thereby 
promoting resilience and health. Depending on the patients’ SOC, when going through a negative life event 
as living with IHD awaiting CABG surgery, the intervention aims to support in terms of understanding and 
involve the availability of the patients’ resources to deal with these events. By identifying appropriate 
resources to cope with stress and encourage the patient to use these resources, making the waiting period 
before heart surgery more understandable, manageable, and meaningful. Involving SOC-enhancing content 

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in this intervention we are  inspired by theory of psycho-educative programs.80, 81 Nurses play a pivotal role 
in delivering psychosocial support to patients undergoing cardiac surgery82 and in this intervention it will be 
provided by trained nurses, who will engage in counselling sessions aimed at equipping patients with coping 
strategies to mitigate stress, anxiety, and depression.83 The preoperative baseline consultation will take place 
in a quiet room in the ward and last for about 30-45 minutes. An inspirational guide will form the basis for 
the consultations. There will be consultation:  at study inclusion, and once a week (by phone) in the waiting 
period until the day before surgery, The participants will be given a phone number to the responsible project 
nurse, who can be contacted in a certain period on working days.  
6.2.4 Smoking cessation intervention 
In this intervention, patients will receive guidance on smoking cessation. During these sessions, a nurse will 
educate the patient about the detrimental effects of smoking on the development and progression of 
ischemic heart disease, emphasizing the negative impact of smoking on their health, particularly before 
surgery, where smoking cessation is strongly recommended.84 As part of the intervention, patients will be 
encouraged to contact the municipal smoking cessation coordinators to arrange a meeting and receive 
further support. The smoking cessation program will include counselling sessions at baseline and weekly 
phone call sessions, along with the provision of nicotine replacement therapy (NRT). NRT will be provided in 
the form of transdermal patches for moderate to heavy smokers, supplemented with individualized doses of 
chewing gum or lozenges, following current guidelines.85 NRT will be distributed during the baseline 
counselling session. The objective of the program is to achieve an 80% reduction in smoking quantity 
(cigarettes per day) before surgery or complete cessation.  
6.2.5 Alcohol cessation intervention 
The approach to support patients in zero alcohol intake before surgery is rooted in the recommendations 
from the Danish Health Authority and the patients are encouraged to completely avoid alcohol intake if the 
patient is assessed a risky drinker (drinking more than 4 alcohol items per day).86 A simple guide of questions 
and advice will be developed for the adherence support to register challenges and encourage adherence to 
support minimizing/avoiding alcohol intake. Assessment, counseling, and support sessions will be organized 
with the social nurse at Rigshospitalet for patients exhibiting hazardous drinking behaviors.  
After the initial face-to-face meeting in the pre-clinic participants will receive three web-based sessions with 
a physiotherapist and one telephone counselling with a nurse per week during the intervention period. 
Detailed protocols for the face-to face counselling and web-based and telephone calls will be developed 
before the outset of the study. 
 

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7. Study outcome measures 
In this CABGpreHAB feasibility study we will explore two types of outcomes: feasibility outcomes and 
explorative clinical outcomes. 
7.1 Primary outcome  
Feasibility outcomes include: 
Recruitment and retention rates. The recruitment rate will be determined by the number of individuals who 
participate in the study out of those who are eligible/admissible but refused to participate. First, we will 
evaluate the number of patients we are able to include in the study during the inclusion period. A proportion 
of 60% or more of patients awaiting elective CABG surgery who are eligible for the study is acceptable. 
Retention will be assessed by the percentage of participants who remain in the study from beginning to end 
of study (30 days post-surgery). 
Attrition rates. Attrition is defined by the number of individuals who give consent to participate in the study 
but drop out before the end of the intervention period, regardless of group allocation. 
Fidelity. Fidelity of delivery of the webcam-based exercise training intervention will be assessed qualitatively 
by 8-10 semi-structured interviews the day before surgery by a research nurse. 
Adherence rates. Adherence to the interventions will be measured by using the number of telephone 
counselling and tele-exercise sessions delivered out of the theoretical number that could have been delivered 
based on the surgical wait time of each participant. Adherence to the homebased tele-exercise training 
sessions and telephone counselling by evaluating the number of sessions applied in the intervention group. 
This will be collected by patient recorded physical activity logbook, by weekly phone calls and completed by 
accelerometer data. Adherence with the prehabilitation program will be assessed against the target of 
individuals achieving > 70% of the prescribed exercise program (self-reported) + during the study follow-up 
with phone calls. Inclusion in the CABGpreHAB study must be attractive to at least 30% of eligible patients 
who meets the inclusion criteria. The interventions must be widely accepted, with at least 70% of included 
participants completing 70% or more of the planned sessions in the intervention group. This will be assessed 
by interviews addressing reasons for withdrawals from the study and at which stage of the study these occur. 
Safety:  Safety of the intervention will be determined based on the number and nature of adverse events 
(AE), which is defined as any discomfort or symptoms of angina pectoris that will prevent a patient to take 
part in the physical tele exercise sessions or symptoms that require medical attention. Adverse event (AE), 
serious AE (SAE), serious adverse reaction (SAR), and suspected unexpected serious adverse reaction (SUSAR) 
will be monitored during the trial counting the number of occurrences. In addition to the physiotherapist 

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taking note of any undesirable effect during and after the tele session or phone counselling with the project 
nurse, all participants are asked to report any symptoms that was not consistent with their usual physical 
condition presentation as a result of exercise sessions. 
For a lager RCT trial to be deemed feasible, feasibility outcomes need to be attained, meaning that more than 
60% of eligible patients will participate and at least 52% of the intervention group will receive more than 60% 
of the intended interventions.87 
7.2 Secondary outcome  
Secondary outcomes shown in Table 1. will assess the patients’ responses to the multimodal prehabilitation 
programme and data will be collected on the following explorative outcomes shown in Table 2, measured at 
baseline, the day before surgery and 30 days after discharge.  
Table 1. The patient related tests and outcome measures  

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Outcome 
variable 
Measurement 
Instrument 
What is the argument for this test or instrument? 
TESTS 
Exercise  
capacity 
6MWT 
(6MWT) measures total walking distance completed in six minutes.88 Functional exercise capacity assessed as change from 
baseline by using the (6MWT) according to the American Thoracic Society guidelines.88 
Muscle  
strength 
30 seconds sit-
to stand 
 Strength and endurance in leg assessed as change from baseline by 30 sec sit-to stand test.89 
Muscle  
strength 
Hand grip 
strength 
The Hand grip strength measures the upper-body physical function assessed by hand grip strength using a hand-held 
dynamometer.90 Frailty assessed from baseline by Hand grip strength.  
Body 
composition 
BIA 
Bio-electrical Impedance Analysis (BIA) estimates values for each body percentage, fat mass, fat-free mass, muscle mass and 
bone mass and total body water are assessed measuring bioelectrical impedance in the body using a Bioelectrical 
Impedance Analyzer.91 
Nutritional 
status 
NRS 2002 + 
BMI, weight, 
height 
Nutritional Risk Screening 2002 (NRS 2002) screening tool is a validated tool attributes scores of different levels of 
nutritional status to patients based on weight loss, BMI, and food intake, considering disease severity (degree of stress 
metabolism) and age. It is a toll recommended for detection of undernutrition and the risk of its development in hospital 
settings. Nutritional status assessed as changed from baseline.78  
Body mass index BMI92 at baseline, 
Daily physical 
activity score 
SENS® motion 
accelerometer 
The SENS motion® system consist of a single-use miniature, waterproof tri-axial accelerometer, and a dedicated smart 
phone application. The accelerator will be placed on the lateral side of the patient’s thigh at the assessment initial with a 
small waterproof Band-Aid. The participants will be asked to wear the SENS-accelerometer continuously for minimum four 
weeks during the intervention period and again post-surgery until end of follow up 30 days post index surgery. Physical 
activity assessed as changed from baseline by accelerator SENS innovation device.75 
QUESTIONAIRES 
Physical 
activity 
Copenhagen 
City Heart 
study 
Self- reported physical activity assessed from baseline by question from Copenhagen City Heart study.93  
A question: “ How physically active are you now?” from the Copenhagen City Heart study  will be used to grade the 
participants physical activity in four levels (level 1-4 , i.e., 1= almost entirely sedentary, 2= light physical activity (PA) for 2-4 
h per week, 3= light PA>4 h per week or more vigorous PA for 2-4 h per week, 4= more vigorous PA >4 h per week or regular 
heavy exercise or competitive sports several times per week. 
HRQOL 
 SF-12 
The SF-12 is a 12-item version of the SF-36 and is a brief, reliable measure of overall health status that generates both a 
physical and a mental component score. The questionnaire measures eight domains of health: physical function (PF), role-
physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE) and mental 
health (MH). Scores are calculated for each domain and aggregated into the mental component score (MCS) and the 
physical component score (PCS). The SF-12 is a suitable questionnaire in studies with large sample sizes having severe 
constraints on questionnaire length and in studies focusing on patient-based assessment of physical and mental health.94 
Health-related quality of life (HRQL) assessed as changed from baseline by Short Form 12 (SF-12).94 

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Heart-specific  
QoL 
HeartQoL 
The HeartQoL questionnaire measures health-related quality of life in patients with ischemic heart disease, specifically 
angina, myocardial infarction, or ischemic heart failure. The questionnaire consists of 14 items and provides two subscales; 
a 10-item physical subscale and a 4-item emotional subscale which are scored from 0 (poor The HeartQoL questionnaire 
measures health-related quality of life) to 3 (The HeartQoL questionnaire measures health-related quality of life better). A 
global score is available if needed. Asks patients to remember how their heart condition has bothered them in the past four 
weeks. The HeartQoL questionnaire measures health-related quality of life allows clinicians and researchers to (a) assess 
baseline The HeartQoL questionnaire measures health-related quality of life, (b) make between-diagnosis comparisons of 
The HeartQoL questionnaire measures health-related quality of life and (c) evaluate changes in The HeartQoL questionnaire 
measures health-related quality of life in patients undergoing interventions to improve patient HRQL.95 
Anxiety 
State-Trait 
Anxiety 
Inventory 
The State-Trait Anxiety Inventory (STAI) is a widely used psychological tool designed to measure two distinct types of 
anxiety. STAI consists of 40 items and is divided into two sections, each containing 20 items. The State-Trait Anxiety 
Inventory (STAI) is a widely used psychological assessment tool designed to measure two types of anxiety in adults: state 
anxiety (S-Anxiety) and trait anxiety (T-Anxiety). State Anxiety (S-Anxiety) reflects a temporary emotional state or 
condition characterized by subjective feelings of tension, apprehension, and nervousness. This type of anxiety fluctuates 
and is typically influenced by situational factors. The STAI measures how anxious an individual feels "right now, at this 
moment." Trait Anxiety (T-Anxiety) refers to a stable personality characteristic, indicating a general tendency to perceive 
situations as threatening and respond with anxiety across time and circumstances. It reflects a person's baseline level of 
anxiety in daily life. The STAI consists of 40 self-report items: 20 items assess state anxiety (e.g., "I feel calm," "I feel 
nervous"), and 20 items assess trait anxiety (e.g., "I am a worrier"). Respondents rate their agreement with each 
statement on a 4-point Likert scale.96 
Depression 
PHQ-4 
Patient Health Questionnaire for depression and Anxiety (PHQ-4) includes four questions, scored on a 4-point Likert scale 
ranging from 0 (“not at all”) to 3 “nearly every day). The questions are: 1. Depression (2 items from PHQ-9): Little interest 
or pleasure in doing things. Feeling down, depressed, or hopeless. Anxiety: (2 items from GAD7): Feeling nervous, anxious, 
or on edge. Not being able to stop or control worrying. Scoring: Each question is scored from 0-3, leading to a total score 
range of 0-12. The total score helps to classify the overall level of psychological distress: 0-2: Minimal or none, 3-5: mild, 6-
8: Moderate, 9-12: Severe.97 
Sense of 
coherence 
SOC-13 
The SOC-13 (Sense of Coherence-13) is a brief version of the Sense of Coherence scale developed by Aaron Antonovsky to 
assess an individual's ability to manage stress and maintain health. It measures three core dimensions: 1. 
Comprehensibility: The extent to which life is perceived as structured and understandable. 2. Manageability: The belief 
that one has the resources to cope with life’s demands. 3. Meaningfulness: The degree to which life is seen as meaningful 
and worth engaging in. The SOC-13 contains 13 items scored on a 7-point Likert scale, with higher scores indicating a 
stronger sense of coherence and better stress resilience.98 

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Self-
efficacy/self-
management 
PAM13 
The PAM13 (patient activation measure) is a 13-item survey, assesses an individual’s knowledge, skill, and confidence for 
self-management. It categorizes patients into four levels based on their activation score, which ranges from a lack of 
understanding of the need for active participation in health (level one) to challenges in maintaining positive health 
behaviors over time (level four).The questionnaire consists of 13 questions, where each question is a statement. 
Respondents indicate on a scale from 1-4 how much they agree with the given statement (1 = strongly disagree, 2 = 
disagree, 3 = agree, 4 = strongly agree). All scores are then summed and divided by the number of answered questions, 
resulting in a score between 13-52. The score is then placed into one of four activity levels below, where level 1 is the 
lowest.99 
Smoking  
status 
Self-reported 
Smoking status assessed as change from baseline. The number of participants successfully quitting smoking out of all 
active smokers 
Alcohol intake 
status 
Self-reported 
Alcohol intake status assessed as change from baseline. The number of participants successfully quitting alcohol 
consumption out of all participants consuming alcohol. 
Patient 
characteristics 
Self-reported 
Age, gender, educational level, employment, civil status 
CR status 
Self-reported 
Last follow up (30 days post index surgery) questionnaire ask about status for: Participating in CR 
Other outcomes DATA 
 
 
 
Adverse 
Events 
Patient record 
Measuring outcomes related to adverse advents for ensuring patient safety 
Complications  
PO 
Patient record 
Complications such as pneumonia, atelectasis, hemorrhage, cardiac arrythmias, delirium 
ICU-LOS/LOS 
Patient record 
Indicator of how well patients are recovering post-surgery and may indicate complications. 
DAOH30 
Patient record 
DAOH30.100,101 Days alive and out of hospital is a composite measure that can be calculated based on available variables and 
proposed as a reliable surgical endpoint. DAOH integrates several clinical outcomes, including death and hospital readmission. 
Biomarkers 
Patient record 
Hgb, albumin, kreatinin, CRP planned as standard blood work at baseline and post intervention. 
 
Abbreviations: BMI: Body Mass Index; BIA: bio electrical Impedance Analysis, CR: cardiac rehabilitation; DAOH30: Days alive out of hospital30; HRQoL: Health 
related quality of life; ICU: Intensive care unit; ICU-LOS: intensive care unit – length of stay; LOS: length of stay; NRS 2002: Nutritional Risk Screening 2002; PO: 
post operative; PAM13: Patient activation measure; PHQ-4: Patient Health Questionnaire for depression and anxiety; SF-12: Short form survey. 
 
 
 

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8. Data collection 
Clinical and sociodemographic data as well as patient-reported outcome measurements will be collected for 
both groups at baseline, the day before surgery, and 30 days post-surgery as shown in Table 2.  
 
 
8.1 Data from questionnaires 
The questionnaires are self-administrated and will be completed electronically in REDCap a web-based data 
capture tool103 which meets the data legislation for logging.  The study participant will receive an email with 
link to a website through which questionnaires can be completed. The e-mail contains a login and password 
for the trial participant’s access. If patients do not complete the questionnaire electronically, the paper 
questionnaires will be handed out to the patient, and independent study personal then enters the responses 
into REDCap. Participants will complete the questionnaires at all three time points: baseline, the day before 
CABG surgery after the intervention, and 30 days post-surgery. The filled-out questionnaires typed in REDCap 
and responses will be stored in a secure folder with limited access (“lovbeskyttet mappe”).  

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8.2 Data from patient records 
Preoperative relevant information, including patient name and age as well as details about the patient’s heart 
diagnosis and medical status (such as Euroscore II, LVEF, and NYHA class), will be reviewed from the patient 
record (SP) without consent by the responsible heart surgeon to inform the study about eligibility of patients  
referred to elective CABG surgery. Additionally, and with consent, postoperative complications, such as 
infections and arrhythmias, along with any adverse events occurring during the intervention period, will be 
documented from the patient record. Information on the length of stay (both ICU-LOS and overall, LOS) and 
the number of days alive out of the hospital within 30 days will be calculated using data from both the patient 
record and Danish registers. Data will be retrieved from the national electronic record system (E-journal) by 
an electronic healthcare software (Epic, Madison, WI, USA), which secures a complete enrolment and follow-
up as the recording is a requirement for economic reimbursement. All data is processed and stored 
confidentially, and personal data will always be handled in accordance with the Danish Data Protection Act 
and the General Data Protection Regulation. Data are stored pseudo-anonymously in a separate approved 
and secure database (Capital Region REDCap), which only the doctors, research assistants and project nurses 
of the study will access using person-specific log-in and password. An anonymous trial number are used as 
patient identification in the REDCap database. The key linking the study-id with the personal id is kept 
separately from the study data with limited access controlled by the study investigator or designee. Authority 
and obligations are documented in the log of delegation of responsibility in the trial. The patient’s records 
will be reviewed by study related personnel to assess clinical and safety endpoints. The informed consent 
gives the investigator and possibly control authority direct access to data from the patient's journal. These 
are used to view information on the participant’s medical condition necessary for the conduct of the study 
and for self-control, quality control and monitoring. The patient is informed about this and gives informed 
consent to this when entering the study. If a potential participant declines to participate in the project, we 
will request permission to collect information regarding their age, gender and current medical status 
pertinent to their admission for CABG surgery and only if a written informed consent is obtained. 
8.3 Data from Danish registries  
A register-based follow-up after 30 days will be used to evaluate DAOH30. The study will use data from the 
following registers: The National Patient Register and The Causes of Death Register. 
8.4 Biological material 
All blood analyses are a part of usual care and the routine blood work when meeting for surgery and will be 
performed according to clinical standards at the hospital and therefore a research biobank will not be 
established.  

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9. Analysis 
9.1 Statistical methods 
Data analysis will be limited to descriptive summary statistics of the proposed endpoints, and calculation of 
feasibility measures, enrollment rates and dropout rates within a period. The feasibility analysis will be based 
on the components of process, resources, management, and scientific approach.58 Process: number of 
eligible patients for enrollment; Successful recruitment rate, rate of adherence to the interventions at each 
time point; Rate of loss to follow up; Rates of completed questionnaires; Understanding of the 
questionnaires. Resources: Time to screen and consent patients, Time to conduct baseline and follow-ups; 
Identification of any challenges related to randomization or data collection; Identification of potential 
barriers of the preoperative programme. Management: Identification of any challenges related to 
randomization or data collection; Identification of potential barriers for the intervention. Scientific approach: 
Estimates of improvement in patient-reported outcomes compared to usual care, patients’ response to 
topics and content in the programme and identification of potentially patient safety issues. As recommended 
for the analysis of pilot studies 58 descriptive statistics will be presented as mean and standard deviations (SD) 
for continuous variables and frequencies and percentages for categorial variables at baseline and follow-ups. 
Collected data on patient characteristics will be presented in tables. Continuous variables will be displayed 
as mean (SD), while categorical variables will be presented as number (n) and percentage (%). Descriptive 
statistics will be used to answer the primary study parameter of feasibility. Feasibility will be presented in 
tables and based on participation rate (n, %), reasons for nonparticipation (n, %, text), adherence to the 
prehabilitation program (%), dropout rates (%), reasons for dropout (n,%, text), adverse advents (n,%, text). 
The secondary aim is to evaluate the patients’ responses over time in terms of physical activity, muscle 
strength, functional capacity, body composition, quality of life and symptoms of depression, and anxiety. A 
repeated measurements analysis will be used to analyze changes over time in continuous variables. P- values 
<0.05 will be considered statistically significant.  
10. Ethics 
10.1 Ethical considerations   
The CABGpreHAB feasibility study will be conducted in accordance with the protocol after approval from the 
Committees on Health Research Ethics in the Capital Region of Denmark,  and according to good clinical 
practice guidelines. This study will comply with the General Data Protection Regulation (GDPR) and the Data 
Protection Act.  All personal data collected during this study will be handled  confidentially and in accordance 
with EU legislation and data security regulations and legislation (GDPR). The principles of the Helsinki 
Declaration in its latest form, and the ICH-GCP guidelines will be followed.103 The protocol will be registered 
on www.clinicaltrials.gov and registered in Privacy before inclusion of the first participant. Substantial 

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amendments to the protocol will not be implemented without the appropriate review and approval by the 
regional ethics committee and the Danish Data Protection Agency, with the exceptions of situations where it 
is necessary to prevent imminent danger to trial participants. In such cases, the amendment will be reported 
to the regional ethics committee.  
10.2 Adverse events and reactions 
10.2.1 Definitions 
Following definitions will be used. 
Adverse Event (AE): any undesirable medical event occurring to a participant during a clinical trial, which 
does not necessarily have a causal relationship with the intervention.104 
Adverse Reaction (AR): any undesirable and unintended medical response related to the intervention 
occurring to a participant during a clinical trial.104  
Serious Adverse Event (SAE): any adverse event that results in death, is life-threatening, requires 
hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or 
incapacity, or is a congenital anomaly or birth defect.104  
Serious Adverse Reaction (SAR): any adverse reaction that results in death, is life-threatening, requires 
hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or 
incapacity, or is a congenital anomaly or birth defect.104 
Suspected Unexpected Serious Adverse Reaction (SUSAR): any suspected adverse reaction which is both 
serious and unexpected (the nature or severity of which is not consistent with the information available to 
date).104,105  
10.2.2 Risk and safety issues in the current trial 
This feasibility study is expected to cause limited risks, side effects and discomfort. Patients are expected to 
benefit from the homebased multimodal prehabilitation program before CABG-surgery. 
10.2.3 Assessment of adverse advents 
The CABGpreHAB feasibility study will be performed according to the GCP guidelines and applicable 
regulatory requirements and legislation. The trial will be conducted according to the Act. No.593 of June 14, 
2011, on Act on Research Ethics Review of Health Research Projects. The investigator will immediately notify 
the regional ethics committee if there, within the intervention period, occur SAEs, SARs or SUSARs. The report 
will be accompanied by comments on possible implications for the trial, and notification will be made within 
7 days after investigator has knowledge of the event. In case of serious adverse reactions, which are results 
of the trial, the investigator will provide the regional ethics committee with the information required. 

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Throughout the trial, annual reports including all expected or unexpected adverse events or reactions will be 
submitted to the ethical committee. Reports will be accompanied by an assessment of the participants safety. 
10.2.4 Severity of adverse events 
The following variables will be registered if an adverse event happens: Description of the event, beginning 
and ending of the event, seriousness (mild, moderate, and serious). Possible casual relation to the 
intervention and actions taken. This will be registered by a project employee and a physician will be involved 
if a serious event occurs or if required in relation to a moderate adverse event. 
10.3 Risks and benefits  
The interventions are expected to cause limited risks, side effects and discomfort. Patients are expected to 
benefit from homebased prehabilitation due to multimodal preoperative preparation before CABG-surgery 
improving functional capacity, reducing symptoms of anxiety and depression. Individualized and optimized 
preoperative care through exercise, supportive nursing counselling will be performed by experienced project 
nurses, physiotherapists and physicians, and patients will not experience any kind of delays or complications 
related to the interventions or follow-up process due to participation in the project. Before commencing the 
exercise components of the prehabilitation program, a physiotherapist will assess the participants' physical 
capacity. Previous studies have demonstrated the safety of preoperative physical exercise programs involving 
mild intensity training in patients scheduled for CABG surgery.6,27,106,107  The physical training regimen will 
adhere to the established recommendations for physical exercise in patients awaiting CABG surgery, ensuring 
the safety and efficacy of the exercise program.108,109 Standard blood sampling, which may cause slight 
discomfort from the needle stick, is expected as part of the procedure.  
10.3.1 Risk and timing of surgery 
Historically waiting time for elective CABG surgery has usually been several weeks, but it has been fluctuating 
between few weeks and up to months. The decision regarding the timing of surgery is typically made 
collaboratively by cardiologists and cardiac surgeons during multidisciplinary team (MDT) conferences.19 This 
decision-making process adheres to current clinical guidelines and is influenced by waiting times dictated by 
local and regional healthcare resources. According to the most recent guidelines published by the American 
College of Cardiology, the prioritization and assessment of patient risk before surgery are central to MDT 
discussions.20For patients with stable angina, timely surgical intervention is advised to prevent progression 
to acute coronary events.110,111 In a Danish context, there is a 30-day recommendation for maximum waiting 
times for elective CABG surgery.113 
 

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10.4 Ensuring integrity and privacy of the participant 
All patient-related information obtained during the feasibility study will be handled in accordance with the 
Danish law for protection of personal data (“lov om behandling af personoplysninger”)113 and the Danish 
health law (“ sundhedsloven”). The 
10.5 Oral information and informed consent 
Prior to consent  all participants receive written and oral information about usual care and the interventions 
included the CABGpreHAB feasibility study, including the Ethics Committee folder “Forsøgspersonens 
rettigheder i et sundhedsvidenskabeligt forskningsprojekt”.114 The participant is informed about the right to 
bring an assessor and the right to consider their participation for a minimum of 24 hours if needed. The oral 
information of the patient and signing of the informed consent form will be conducted in a closed off room 
to ensure that the information is given under undisturbed circumstances and are carried out by the 
investigator or substitute directly involved in the trial, who have the necessary experience and competence. 
When the information is given, it is emphasized that participation is voluntary. A patient can be withdrawn 
from the study at any time, if it is the wish of the patient, or if it is medically indicated, as judged by the 
investigator. Participation in the study is discontinued, if any of the following criteria applies a) the patient’s 
general condition contraindicates continuing the study or b) the patient turns out to be non-eligible patient.  
11. Legal and organizational aspects 
11.1 Quality control and quality assurance 
All data will be entered into a study database for analysis and reporting. Any data captured electronically will 
be stored electronically in a separate database according to standard procedures at Rigshospitalet. Upon 
completion of data entry, the databases will be checked to ensure acceptable accuracy and completeness. 
System backups and record retention for the study data will be consistent with Rigshospitalet’ s standard 
procedures. Source data will be recorded in the electronic patient record or on specific worksheets. An 
electronic Case Report Form (eCRF) will be constructed for data capture. The investigators are responsible 
for ensuring the accuracy, completeness, legibility, and timeliness of the data recorded in the eCRFs.  
11.2 Economy 
The study is an investigator-initiated trial conceived and conducted by The Department of Cardiothoracic 
Surgery, The Heart Centre, Copenhagen University Hospital. The idea for the project originated from DBO 
and the department of Cardiothoracic surgery at the Heart Centre at Rigshospitalet. The trial will be funded 
by external funds for research in health sciences. All grants will be paid to the financial office at Rigshospitalet 
and will be used for salaries for the trial staff and other research related to expenses. No compensation is 
granted to trial participants or transport expenses. None of the persons responsible for the trial have any 

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financial affiliation with the funds applied for. If such funding is achieved the ethical committees will be 
informed of the donator, and value of the grant, and the written patient information material will be updated 
with all donators mentioned. Any received funds will be deposited to a project specific research account, 
which is administrated by the hospital and under public revision. The CABGpreHAB trial has been supported 
by research grants from: The Heart Centre research foundation on the amount of 204.000 DKK, Helsefonden 
300.000 DKK (ID: 23-B-0122), Trygfonden 600.000 DKK (ID159457) and PhD. Stipendium from Rigshospitalet 
Forskningspulje. These funds are used for salaries, running costs and equipment during the project period. 
11.3 Insurance 
According to the Act on right of appeal and compensation within the National Health Service (Act No. 547 of 
24 June 2005) all trial participants are covered by the Patient Assurance Association and will be informed 
about this prior to inclusion. Sponsors, researchers, and trial nurse are covered by the statutory insurance at 
the hospital.  
11.4 Plan for publication, authorship, and dissemination 
After approval of the ethics application by the Regional Scientific Committee, The Capital of Copenhagen, the 
feasibility study will be registered on www.ClinicalTrials.gov before randomization of patients start. Results 
of the study will be analyzed by an independent statistician, and the results will be interpreted by the 
research group. The conclusion will be prepared in in two versions, before the allocation code is broken, with 
the two arms alternately assumed as intervention (one that assumes that arm A is the intervention, and 
second, that assumes that the arm B is the intervention). Positive, negative and inconclusive results of the 
CABGpreHAB feasibility study will be published. The final manuscripts emanating from the study will be sent 
to a “peer reviewed” international journal. Authorship will be allocated using the guidelines for Proposal 
authorship defined by the international Committee of medical journal Editors and depends on the personal 
involvement. A minimum of three scientific papers are planed based on CABGpreHAB trial. To reach policy 
makers, administrators and healthcare professionals, the project will be presented in thoracic surgery, 
cardiology, nursing, and physiotherapy journals. To gain broader interest, national patient associations will 
be contacted. 
11.5 Trial timeline 
The CABGpreHAB feasibility study will begin in May 2025, after approval by the Regional Ethics Committee 
in the Capital Region, with inclusion of the first participants. The inclusion will end in May 2026 with the last 
follow-up in June 2026. The end-of-study is defined as the date of the last patient`s follow-up assessment. 

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12. Organization   
The research team comprises a multidisciplinary group with a strong scientific and clinical background. This 
protocol has been developed through close collaboration among all members of the research group listed 
below. The primary responsibility for developing the core elements of the multimodal intervention has been 
undertaken by Christian Have Dall, Rikke Krogh Madsen, Maria Hein Hegelund, Sune Damgaard, Ida Elisabeth 
Højskov and Dorte Bæk Olsen. Responsibility for data management is placed in Department of Cardiothoracic 
Surgery, The Heart Centre, Rigshospitalet. 
 
Ida Elisabeth Højskov1,2 Primary investigator 
Dorte Bæk Olsen1 Project leader 
Sune Damgaard1 Primary responsible physician / surgeon 
Selina Kikkenborg Berg2 Nurse, professor of cardiology 
Malene Missel1 Nurse, senior researcher 
Christian Have Dall3 Physiotherapist, senior researcher 
Mette Frahm Olsen4 MSc, senior researcher 
Daniel Faurholt-Jepsen4 MD, senior researcher 
Rikke Krogh-Madsen5 MD, senior researcher 
Henning Bundgaard2 MD, professor of cardiology 
Maria Hein Hegelund4 MSc, Post Doc 
Ann Dorthe Zwisler6 MD, professor of rehabilitation 
 
Affiliations: 
1Department of Cardiothoracic surgery, Copenhagen University Hospital, Rigshospitalet 
2Department of Cardiology, Copenhagen University Hospital, Rigshospitalet 
3Department of Cardiology, Copenhagen University Hospital, Bispebjerg-Frederiksberg. 
4Department of Infectious Disease, Copenhagen University Hospital, Rigshospitalet 
5Centre for Physical Activity Research, Copenhagen University Hospital – Rigshospitalet, Copenhagen 
6 CKO, Copenhagen University Hospital – Rigshospitalet, Copenhagen 
 
 

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13. References 
1. Waite I, Deshpande R, Baghai M, Massey T, Wendler O, Greenwood S. Home-based preoperative 
rehabilitation (prehab) to improve physical function and reduce hospital length of stay for frail 
patients undergoing coronary artery bypass graft and valve surgery. J Cardiothorac Surg 2017;12 
(1):1–7.  
2. Bruce KM, Yelland GW, Smith JA, Robinson SR. Recovery of cognitive function after coronary artery 
bypass graft operations. Ann Thorac Surg 2013;95(4):1306–13. 
3. Totonchi Z, Seifi S, Chitsazan M, Ghavidel AA, Baazm F, Faritus SZ. Pain Location and Intensity During 
the First Week Following Coronary Artery Bypass Graft Surgery. Anesth Pain Med 2013;4(1):1-7. 
4. Engelman DT, Ben Ali W, Williams JB, Perrault LP, Reddy VS, Arora RC, et al. Guidelines for 
Perioperative Care in Cardiac Surgery: Enhanced Recovery after Surgery Society Recommendations. 
JAMA Surg. 2019; 12:1–12. 
5. McCann M, Stamp N, Ngui A, Litton E. Cardiac Prehabilitation. J Cardiothorac Vasc Anesth 
2019;33(8):2255-65 
6. Sawatzky JA, Kehler DS, Ready AE, Lerner N, Boreskie S, Lamont D, et al. Prehabilitation program for 
elective coronary artery bypass graft surgery patients: a pilot randomized controlled study. Clin 
Rehabil 2014;28(7):648-57. 
7. Steinmetz, Carolin PhD; Bjarnason-Wehrens, Birna PhD; Walther, Thomas MD; Schaffland, Tim Fabian 
PhD; Walther, Claudia MD. Efficacy of Prehabilitation Before Cardiac Surgery: A Systematic Review 
and Meta-analysis. American Journal of Physical Medicine & Rehabilitation 102(4):p 323-330, April 
2023 
8. Tadayon S, Wickramasinghe K, Townsend N. Examining trends in cardiovascular disease mortality 
across Europe: how does the introduction of a new European Standard Population affect the 
description of the relative burden of cardiovascular disease? Popul Health Metr. 2019;17(1):1-3 
9. Timmis A, Vardas P, Townsend N, Torbica A, Katus H, De Smedt D, et al. European Society of 
Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022 Feb;43(8):716–99 
10. Sundhedsdatastyrelsen 
11. Dødsårsagsregistret 2022 
12. Dansk 
hjerteregister. 
Årsrapport 
2022. 
1. 
januar 
2022-31.december 
2022. 
https://www.sundhed.dk/content/cms/72/4672_dhreg_aarsrapport-2022.pdf, Version 29.06.2024 
13. The Danish Heart Foundation. Danish heart statistic 2022 Hjerteforeningen. Fakta om hjerte-kar-
sygdom i Danmark. Https://hjerteforeningen.dk/alt-om-dit-hjerte/noegletal/. 
14. Mairey I, Rosenkilde S. Klitgaard MB, Thygesen LC. Sygdomsbyrden I Danmark – Sygdomme. 
København: Sundhedsstyrelsen: 2022 
15. https://www.sst.dk/-/media/Udgivelser/2023/Sygdomsbyrden-2023/Sygdomme-Sygdomsbyrden-
2023.ashx?sc_lang=da&hash=D5A3E38D69ED707803158DEF28BBAA9F 
16. Institute of Medicine (US) Committee on Social Security Cardiovascular Disability Criteria. 
Cardiovascular Disability: Updating the Social Security Listings. Washington (DC): National Academies 
Press(US);2010.7,IschemicHeartDisease. Availablefrom:https://www.ncbi.nlm.nih.gov/books/NBK20
9964/ 
17. Juel K. Hjerte-kar-sygdomme – En vurdering af rygningens betydning for dødeligheden og nye tilfælde. 
https://hjerteforeningen.dk/wp-content/uploads/2019/11/rapport-hjertekarsygdomme-rygning.pdf 

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
33 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
18. Kotseva K, De Backer G, De Bacquer D, Rydén L, Hoes A, Grobbee D, et al. Lifestyle and impact on 
cardiovascular risk factor control in coronary patients  across 27 countries: Results from the European 
Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardiol. 2019 May;26(8):824–35 
19. Sousa-Uva M, Neumann FJ., Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. ESC Scientific 
Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothorac 
Surg. 2019; 55(1): 18-21. Eller 
20. Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI 
Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American 
College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. 
Circulation. 2022 Jan;145(3):e4–17 
21. The 
Danish 
Heart 
Register 
https://www.rkkp.dk/kvalitetsdatabaser/databaser/dansk-
hjerteregister/nyheder-fra-dansk-hjerteregister-dhr/arsrapport-2023-fra-dansk-hjerteregister/ 
22. The Department of Cardiothoracic Surgery local database (2021). Copenhagen University Hospital 
Rigshospitalet. 
23. Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, et al. 2011 ACCF/AHA guideline for 
coronary artery bypass graft surgery: executive summary: a report of the American College of 
Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac 
Cardiovasc Surg. 2012 Jan;143(1):4–34. 
24. Doenst T, Schneider U, Caldonazo T, Toshmatov S, Diab M, Siemeni T, et al. Cardiac Surgery 2022 
Reviewed. Thorac Cardiovasc Surg. 2023 Aug;71(5):356–65. 
25. Caldonazo T, Kirov H, Riedel LL, Gaudino M, Doenst T. Comparing CABG and PCI across the globe based 
on current regional registry evidence. Sci Rep. 2022 Dec;12(1):22164. 
26. Jawitz OK, Gulack BC, Brennan JM, Thibault DP, Wang A, O’Brien SM, et al. Association of 
postoperative complications and outcomes following coronary artery  bypass grafting. Am Heart J. 
2020 Apr;222:220–8. 
27. Arthur HM, Daniels C, McKelvie R, Hirsh J, Rush B. Effect of a preoperative intervention on 
preoperative and postoperative outcomes in low-risk patients awaiting elective coronary artery 
bypass graft surgery: a randomized controlled trial. Ann Intern Med 2000;133(4):253–62. 
28. Mooney M, Fitzsimons D, Richardson G. “No more couch-potato!” Patients’ experiences of a pre-
operative programme of cardiac rehabilitation for those awaiting coronary artery bypass surgery. Eur 
J of Cardiovasc Nurs 2007;6(19): 77–83. 
29. Feuchtinger J, Burbaum C, Heilmann C, Imbery C, Siepe M, Stotz U, et al. Anxiety and fear in patients 
with short waiting times before coronary artery bypass surgery – a qualitative study. J Clin Nurs 
2014;23 (13-14):1900–7.  
30. Same RV, Feldman DI, Shah N, Martin SS, Al Rifai M, Blaha MJ, et al. Relationship Between Sedentary 
Behavior and Cardiovascular Risk. Curr Cardiol Rep 2016;18(1):1-7. 
31. The Cross-Sectional Study, The Heart Center, Rigshospitalet, DK-Copenhagen, 2019 
32. Carli, F., & Zavorsky, G. S. (2005). Optimizing functional exercise capacity in the elderly surgical 
population. Current Opinion in Clinical Nutrition and Metabolic Care, 8(1), 23–32. 
https://doi.org/10.1097/00075197-200501000-00005 
33. Steinmetz C, Krause L, Sulejmanovic S, Kaumkötter S, Mengden T, Grefe C, et al. The prevalence and 
impact of sarcopenia in older cardiac patients undergoing inpatient cardiac rehabilitation - results 
from a prospective, observational cohort pre-study. BMC Geriatr. 2024 Jan;24(1):94. 

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
34 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
34. Stoppe C, Whitlock R, Arora RC, Heyland DK. Nutrition support in cardiac surgery patients: Be calm 
and feed on! Vol. 158, The Journal of thoracic and cardiovascular surgery. United States; 2019. p. 
1103–8. 
35. Chermesh I, Hajos J, Mashiach T, Bozhko M, Shani L, Nir R-R, et al. Malnutrition in cardiac surgery: 
food for thought. Eur J Prev Cardiol. 2014 Apr;21(4):475–83. 
36. Bayir H, Tekelioglu ÛY, Kocoglu H, et al. investigating of malnutrion rates and related risk factors in 
open heart surgery. Journal of Cardio-Vascular-Thoracic Anaesthesia and Intensive Care Society 2014; 
20(4):209-214 
37. Lomivorotov V V, Efremov SM, Boboshko VA, Nikolaev DA, Vedernikov PE, Deryagin MN, et al. 
Prognostic value of nutritional screening tools for patients scheduled for  cardiac surgery. Interact 
Cardiovasc Thorac Surg. 2013 May;16(5):612–8. 
38. Mills E, Eyawo O, Lockhart I, Kelly S, Wu P, Ebbert JO. Smoking cessation reduces postoperative 
complications: a systematic review and  meta-analysis. Am J Med. 2011 Feb;124(2):144-154.e8. 
39. Eliasen M, Grønkjær M, Skov-Ettrup LS, Mikkelsen SS, Becker U, Tolstrup JS, et al. Preoperative alcohol 
consumption and postoperative complications: a systematic  review and meta-analysis. Ann Surg. 
2013 Dec;258(6):930–42. 
40. Best MJ, Buller LT, Gosthe RG, Klika AK, Barsoum WK. Alcohol Misuse is an Independent Risk Factor 
for Poorer Postoperative Outcomes  Following Primary Total Hip and Total Knee Arthroplasty. J 
Arthroplasty. 2015 Aug;30(8):1293–8. 
41. https://www.sst.dk/-/media/Udgivelser/2018/Anbefalinger-for-tvaersektorielle-forloeb-for-
mennesker-med-hertesygdom.ashx 
42. Benedetto U, Albanese A, Kattach H, Ruggiero D, De Robertis F, Amrani M, et al. Smoking cessation 
before coronary artery bypass grafting improves operative  outcomes. J Thorac Cardiovasc Surg. 2014 
Aug;148(2):468–74. 
43. https://www.sst.dk/da/Borger/En-sund-hverdag/Rygning,-nikotin-og-snus/Rygestop/Rygning-og-
operation 
44. https://www.sst.dk/da/Borger/En-sund-hverdag/Alkohol/Alkohol-og-operation 
45. Weimann A, Wobith M. ESPEN Guidelines on Clinical nutrition in surgery - Special issues to be 
revisited. Eur J Surg Oncol J Eur Soc  Surg Oncol Br Assoc Surg Oncol. 2024 May;50(5):106742. 
46. Grant MC, Crisafi C, Alvarez A, Arora RC, Brindle ME, Chatterjee S, et al. Perioperative Care in Cardiac 
Surgery: A Joint Consensus Statement by the Enhanced Recovery After Surgery (ERAS) Cardiac Society, 
ERAS International Society, and The Society of Thoracic Surgeons (STS). Vol. 117, The Annals of 
thoracic surgery. Netherlands; 2024. p. 669–89. 
47. Levy N, Selwyn DA, Lobo DN. Turning “waiting lists” for elective surgery into “preparation lists”. Vol. 
126, British journal of anaesthesia. England; 2021. p. 1–5. 
48. Sawalha O, Ariza-Vega P, Alhalaiqa F, Pérez-Rodríguez S, Romero-Ayuso D. Psychological Discomfort 
in Patients Undergoing Coronary Artery Bypass Graft (CABG) in West Bank: A Cohort Study. J Clin Med. 
2024 Mar;13(7). 
49. Arora RC, Brown CH 4th, Sanjanwala RM, McKelvie R. “NEW” Prehabilitation: A 3-Way Approach to 
Improve Postoperative Survival and Health-Related Quality of Life in Cardiac Surgery Patients. Can J 
Cardiol. 2018 Jul;34(7):839–49. 
50. Olsen DB, Pedersen PU, Noergaard MW. Prehabilitation before elective coronary artery bypass 
grafting surgery: a scoping review. JBI Evid Synth. 2023 Jun;21(6):1190–242.  

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
35 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
51. Peters MDJ, Marnie C, Tricco AC, Pollock D, Munn Z, Alexander L, et al. Updated methodological 
guidance for the conduct of scoping reviews. JBI Evid Synth. 2020 Oct;18(10):2119–26. 
52. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 
statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar;372: n71. 
53. Marmelo F, Rocha V, Moreira-Gonçalves D. The impact of prehabilitation on post-surgical 
complications in patients undergoing non-urgent cardiovascular surgical intervention: Systematic 
review and meta-analysis. Eur J of Prev Cardiol 2018;25(4):404-17.  
54. Arora RC, Brown CH, Sanjanwala RM, Mckelvie R.“NEW ” Prehabilitation : A 3-Way Approach to 
Improve Postoperative Survival and Health-Related Quality of Life in Cardiac Surgery Patients. Can J 
Cardiol 2018;34(7):839–49.  
55. Bargnes, V., III; Davidson, S.; Talbot, L.; Jin, Z.; Poppers, J.; Bergese, S.D. Start Strong, Finish Strong: A 
Review 
of 
Prehabilitation 
in 
Cardiac 
Surgery. Life 2024, 14, 
832. 
https://doi.org/10.3390/life14070832 
56. Yamikan, H., Ahiskali, G. N., Demirel, A., & Kütükcü, E. C. (2025). The effects of exercise-based 
prehabilitation in patients undergoing coronary artery bypass grafting surgery: A systematic review 
of randomized controlled trials. Heart & Lung, 69, 41–50. 
https://doi.org/10.1016/j.hrtlng.2024.09.007 
57. Bhatt H V, Fritz AV, Feinman JW, Subramani S, Malhotra AK, Townsley MM, et al. The Year in 
Cardiothoracic and Vascular Anesthesia: Selected Highlights From 2023. J Cardiothorac Vasc Anesth. 
2024 Jan;38(1):16–28. 
58. Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, et al. Defining Feasibility 
and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual 
Framework. PLoS One. 2016;11(3): e0150205. 
59. Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for 
developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ. 
2021 Sep; 374: n2061.  
60. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 
statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb;158(3):200–
7. 
61. Boutron I, Altman DG, Moher D, Schulz KF, Ravaud P. CONSORT Statement for Randomized Trials of 
Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial 
Abstracts. Ann Intern Med. 2017 Jul;167(1):40–7. 
62. Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A tutorial on pilot studies: what, why and 
how. BMC Med Res Methodol. 2010 Jan; 10:1. 
63. Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to 
considerations of precision and efficiency. J Clin Epidemiol. 2012 Mar;65(3):301–8. 
64. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4: 287-291 
65. Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008 
Apr;31(2):180–91. 
66. Steinmetz C, Heinemann S, Kutschka I, Hasenfuß G, Asendorf T, Remppis BA, et al. Prehabilitation in 
older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter 
randomized controlled trial. Trials. 2023 Aug;24(1):533.  

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
36 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
67. Steinmetz C, Bjarnason-Wehrens B, Baumgarten H, Walther T, Mengden T, Walther C. Prehabilitation 
in patients awaiting elective coronary artery bypass graft surgery - effects on functional capacity and 
quality of life: a randomized controlled trial. Clin Rehabil. 2020 Oct;34(10):1256–67. 
68. Martin CG, Turkelson SL. Nursing care of the patient undergoing coronary artery bypass grafting. J 
Cardiovasc Nurs. 2006;21(2):109–17. 
69. https://intranet.regionh.dk/pim/Lists/PDPDocuments/Hjerteoperation---tiden-inden-og-selve-
indlaeggelsen-267063.pdf 
70. https://www.rigshospitalet.dk/afdelinger-og-klinikker/hjerte/hjerte-og-lungekirurgi/undersoegelse-
og-behandling/hjerteoperation-paa-voksne/Sider/default.aspx 
71. https://intranet.regionh.dk/pim/Lists/PDPDocuments/Kost-og-aktivitet-foer-og-efter-operation-
30967.pdf 
72. Blumenau Pedersen M, Saxton J, Birch S, Rasmussen Villumsen B, Bjerggaard Jensen J. The use of 
digital technologies to support home-based prehabilitation prior to major surgery: A systematic 
review. Surgeon. 2023 Dec;21(6): e305–15. 
73. Zhong W, Fu C, Xu L, Sun X, Wang S, He C, et al. Effects of home-based cardiac telerehabilitation 
programs in patients undergoing percutaneous coronary intervention: a systematic review and 
meta-analysis. BMC Cardiovasc Disord. 2023;23(1):101. 
74. Taylor JL, Bonikowske AR, Olson TP. Optimizing Outcomes in Cardiac Rehabilitation: The Importance 
of Exercise Intensity. Front Cardiovasc Med. 2021;8:734278 
75. Bartholdy C, Gudbergsen H, Bliddal H, Kjærgaard M, Lykkegaard KL, Henriksen M. Reliability and 
Construct Validity of the SENS Motion® Activity Measurement System as a Tool to Detect Sedentary 
Behaviour in Patients with Knee Osteoarthritis. Arthritis. 2018; 2018:6596278. 
76. Hwang R, Bruning J, Morris NR, Mandrusiak A, Russell T. Home-based telerehabilitation is not inferior 
to a centre-based program in patients with chronic heart failure: a randomised trial. J Physiother. 
2017 Apr;63(2):101–7. 
77. Hansen H, Bieler T, Beyer N, Kallemose T, Wilcke JT, Østergaard LM, et al. Supervised pulmonary tele-
rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicenter trial. 
Thorax. 2020 May;75(5):413–21. 
78. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M; Educational and Clinical Practice Committee, 
European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN guidelines for nutrition 
screening 2002. Clin Nutr. 2003 Aug;22(4):415-21.  
79. Antonovsky A. (1979) Health, Stress, and Coping: New Perspective on Mental and Physical Well-Being. 
San Francisco, CA: Jossey-Bass. 
80. Oliveira P, Porfírio C, Pires R, Silva R, Carvalho JC, Costa T, et al. Psychoeducation Programs to Reduce 
Preoperative Anxiety in Adults: A Scoping Review. Int J Environ Res Public Health. 2022 Dec;20(1). 
81. Leventhal H, Phillips LA, Burns E. The Common-Sense Model of Self-Regulation (CSM): a dynamic 
framework for  understanding illness self-management. J Behav Med. 2016 Dec;39(6):935–46 
82. Salzmann S, Salzmann-Djufri M, Wilhelm M, Euteneuer F. Psychological Preparation for Cardiac 
Surgery. Curr Cardiol Rep. 2020 Oct;22(12):172. 
83. Powell, R., Scott, N. W., Manyande, A., Bruce, J., Vögele, C., Byrne-Davis, L. M., Unsworth, M., 
Osmer, C., & Johnston, M. (2016). Psychological preparation and postoperative outcomes for adults 
undergoing surgery under general anaesthesia. Cochrane Database of Systematic Reviews, 2016(5).  
84. Duncan MS, Freiberg MS, Greevy RAJ, Kundu S, Vasan RS, Tindle HA. Association of Smoking Cessation 
with Subsequent Risk of Cardiovascular Disease. JAMA. 2019 Aug;322(7):642–50. 

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
37 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
85. https://www.sst.dk/-/media/Udgivelser/2024/Nikotinafhaengighed/Behandling-af-
nikotinafhaengighed.ashx 
86. https://www.sst.dk/-/media/Udgivelser/2020/Alkohol-og-operation/FOLDER-Alkohol-og-operation-
maj-2023.ashx 
87. Riberholt CG, Lindschou J, Gluud C, Mehlsen J, Møller K. Early mobilisation by head-up tilt with 
stepping versus standard care after  severe traumatic brain injury - Protocol for a randomised clinical 
feasibility trial. Trials. 2018 Nov;19(1):612. 
88. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 
Jul;166(1):111–7. 
89. Alcazar J, Losa-Reyna J, Rodriguez-Lopez C, Alfaro-Acha A, Rodriguez-Mañas L, Ara I, et al. The sit-to-
stand muscle power test: An easy, inexpensive, and portable procedure to assess muscle power in 
older people. Exp Gerontol. 2018 Oct; 112:38–43. 
90. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement 
of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing 
2011 Jul; 40:423–429,  
91. Popiolek-Kalisz J, Szczygiel K. Bioelectrical Impedance Analysis and Body Composition in 
Cardiovascular Diseases. Curr Probl Cardiol. 2023 Nov;48(11):101911. 
92. Zierle-Ghosh A, Jan A. Physiology, Body Mass Index. [Updated 2023 Nov 5]. In: StatPearls [Internet]. 
TreasureIslan(FL):StatPearlsPublishing;2024Jan-. Availablefrom: 
https://www.ncbi.nlm.nih.gov/books/NBK535456/ 
93. Schnohr P, Jensen GB, Lange P, Scharling H, Appleyard M. The Copenhagen City Heart Study - 
Østerbroundersøgelsen. Tables with data from the third examination 1991-1994. Euro Heart J. 2001 
94. Ware JJ, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and 
preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220–33. 
95. Oldridge N, Höfer S, McGee H, Conroy R, Doyle F, Saner H. The HeartQoL: part II. Validation of a new 
core health-related quality of life questionnaire for patients with ischemic heart disease. Eur J Prev 
Cardiol. 2014 Jan;21(1):98–106. 
96. Spielberger, C. D., Gorsuch, R. L., Lushene, R., Vagg, P. R., & Jacobs, G. A. (1983). Manual for the State-
Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press. 
97. Kroenke, K., Spitzer, R. L., Williams, J. B. W., & Lowe, B. (2009). An Ultra-Brief Screening Scale for 
Anxiety and Depression: The PHQ-4. Psychosomatics, 50(6), 613–621. 
https://doi.org/10.1176/appi.psy.50.6.613 
98. Antonovsky A. The structure and properties of the sense of coherence scale. Social science & 
medicine (1982). 1993;36(6):725-33. 
99. Maindal HT, Sokolowski I, Vedsted P. Translation, adaptation, and validation of the American short 
form Patient Activation Measure (PAM13) in a Danish version. BMC Public Health. 2009;9:209. 
100. 
Jerath A, Wallis CJD, Fremes S, Rao V, Yau TM, Heybati K, et al. Days alive and out of hospital 
for adult female and male cardiac surgery patients: a population-based cohort study. BMC Cardiovasc 
Disord. 2024 Apr;24(1):215. 
101. 
Myles PS, Shulman MA, Heritier S, Wallace S, McIlroy DR, McCluskey S, et al. Validation of days 
at home as an outcome measure after surgery: a prospective cohort study in Australia. BMJ Open. 
2017 Aug;7(8): e015828. 

Protocol: CABGpreHAB 
 
Version 5.0 20-05-2025 
38 
Project identification H-24070198/ tillægsanmeldelsesnr: 116943 
102. 
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)--a metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform. 2009 Apr;42(2):377–81. 
103. 
World Medical Association.  World Medical Association Declaration of Helsinki: ethical 
principles for medical research involving human participants.  JAMA. Published online October 19, 
2024.  
104. 
ICH Harmonised Guideline. Integrated addendum to ICH E6(R1). Guideline for Good Clinical 
Practice E6(R2), (2016). 
105. 
DeMets DL, Furberg CD, Friedman LM. Data Monitoring in Clinical Trials: A Case Studies 
Approach. 1 ed. New York, NY 10013, USA: Springer Science Business Media, Inc.; 2006. 374  
106. 
Stammers AN. Optimizing the Pre-Operative Risk Profile of Older Adults Undergoing Elective 
Cardiac Surgery: A Randomized Controlled Trial [Internet]. 2016 [cited 2021 Apr 11]. A Master Thesis, 
Faculty of Kinesiology and Recreation Management University of Manitoba, Canada 
107. 
Steinmetz C, Bjarnason-Wehrens B, Baumgarten H, Walther T, Mengden T, Walther C. 
Prehabilitation in patients awaiting elective coronary artery bypass graft surgery - effects on 
functional capacity and quality of life: a randomized controlled trial. Clin Rehabil. 2020 
Oct;34(10):1256–67 
108. 
https://www.cardio.dk/media/com_reditem/files/customfield/item/6630/Fysisk_tr%C3%A6
ning_ved_isk%C3%A6misk_hjertesygdom.pdf 
109. 
Virani SS, Newby LK, Arnold S V, Bittner V, Brewer LC, Demeter SH, et al. 2023 
AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients with Chronic Coronary 
Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee 
on Clinical Practice Guidelines. Circulation. 2023 Aug;148(9): e9–119. 
110. 
Head, S. J., da Costa, B. R., Beumer, B., Stefanini, G. G., Alfonso, F., Clemmensen, P. M., Collet, 
J.-P., Cremer, J., Falk, V., Filippatos, G., Hamm, C., Kappetein, A. P., Kastrati, A., Knuuti, J., Kolh, P., 
Landmesser, U., Laufer, G., Neumann, F.-J., Richter, D. J., … Sousa-Uva, M. (2017). Adverse events 
while awaiting myocardial revascularization: a systematic review and meta-analysis. European Journal 
of Cardio-Thoracic Surgery, 52(2), 206–217. https://doi.org/10.1093/ejcts/ezx115 
111. 
Rexius, H., Brandrup-Wognsen, G., Nilsson, J., Odén, A., & Jeppsson, A. (2006). A Simple Score 
to Assess Mortality Risk in Patients Waiting for Coronary Artery Bypass Grafting. The Annals of 
Thoracic Surgery, 81(2), 577–582. https://doi.org/10.1016/j.athoracsur.2005.08.032 
112. 
https://www.sst.dk/da/Borger/Patientrettigheder/Maksimale-ventetider-ved-kraeft-og-
hjertesygdom/Angina-pectoris-smerter-umiddelbart-efter-akut-myokardieinfarkt 
113. 
https://www.retsinformation.dk/eli/lta/2018/502 
114. 
https://www.retsinformation.dk/eli/lta/2022/210