Prehabilitation for people undergoing cardiac surgery

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

The overarching aim of this review is to determine the benefits and harms of prehabilitation on postoperative outcomes in people undergoing cardiac surgery. The specific objectives are:

• to identify and describe all prehabilitation interventions that have been administered prior to cardiac surgery (urgent and elective pathways);

• to compare the effectiveness of the different interventions against no intervention or usual care on postoperative and long‐term outcomes (general and cardiac surgery‐specific); and

• to identify the harms associated with prehabilitation interventions.

Background

Description of the condition

This systematic review will focus on people undergoing cardiac surgery, including coronary artery bypass graft (CABG) surgery, aortic surgery (thoracic aorta), and valve surgery. Worldwide, over one million cardiac surgery procedures take place every year, mainly in high‐income countries (Vervoort 2021). Compared to other surgical populations, people undergoing cardiac surgery are older (67 years versus 54 years) and have a higher comorbidity burden (average Charlson score 2.1 versus 1.7; Richens 2018). They experience physical and mental deconditioning because of the high burden of comorbid disease (e.g. obesity, diabetes, and lung disease) and because the cardiac disease process itself limits physical activity. Frailty affects between 20% and 32% of people who undergo cardiac surgery (Ad 2016; Brown 2016; Montgomery 2020), and sarcopenia (loss of muscle mass and function) affects between 13% and 27% of this population (Joshi 2021; Okamura 2019; Yuenyongchaiwat 2020). Both frailty and sarcopenia are associated with a higher likelihood of adverse postoperative outcomes (Sepehri 2014). Preoperative depression is also common, affecting up to 45% of people undergoing cardiac surgery, and is associated with reduced cardiac symptom relief, impaired quality of life, and increased mortality after surgery (Blumenthal 2003; Huffman 2013; Rumsfeld 2004). These preoperative risk factors influence the risk of developing postoperative complications and impair both short‐ and long‐term recovery (Richens 2018).

One analysis of postoperative complications in 26,221 people who underwent cardiac surgery from 1993 to 2019 revealed a prevalence of 67% (Pahwa 2021). Complications such as stroke, renal failure, and pneumonia had the greatest impact on long‐term survival. Therefore, targeted interventions to reduce postoperative complications could improve not only short‐term recovery, but also long‐term outcomes, reducing lifetime healthcare cost.

The 2020 UK National Adult Cardiac Surgery Audit showed a mean waiting time for elective CABG surgery of 107 days in 2018/19 (National Adult Cardiac Surgery Audit 2020). This is likely to increase due to the surgery backlog resulting from the coronavirus disease 2019 (COVID‐19) pandemic, with cancellations and delays to elective procedures occurring across all specialties (Dobbs 2021). In the long period of time from a person being listed for surgery to the operation taking place, clinicians could deliver targeted interventions to prevent postoperative complications and thus improve short‐ and long‐term surgical outcomes.

Description of the intervention

Prehabilitation is a broad term that refers to interventions administered before surgery to improve health and physical/mental fitness and thus reduce the risk of surgery‐related morbidity and facilitate recovery. Prehabilitation focusses on the preventive approach by targeting modifiable risk factors for morbidity and mortality and optimising them to reduce the incidence of adverse postoperative outcomes.

We define prehabilitation as any non‐pharmacological and non‐procedural intervention administered prior to surgery with the aim of improving physical and mental health and well‐being to maximise resilience to the treatment (cardiac surgery), enhance the quality of recovery, and improve postoperative outcomes and long‐term health (Prehabilitation for People with Cancer).

Prehabilitation interventions are generally regarded as low risk to patients. They typically involve changes in people's behaviour, supported by guidance and advice from healthcare professionals. The Types of interventions section of this protocol provides a list of the different intervention components that can be included in a prehabilitation programme.

How the intervention might work

The mechanisms of action of prehabilitation interventions vary depending on the risk factor they target.

Exercise interventions improve cardiovascular function, which is an important predictor of mortality in older people undergoing cardiac surgery (Sui 2007). Research has shown an association between poor cardiovascular fitness and higher all‐cause mortality (Mandsager 2018). However, it is unclear which type of exercise programme is best for improving surgical outcomes (e.g. a programme based on moderate intensity and endurance training to target overall fitness, or one based on high‐intensity interval training to improve peak/maximal physical function.)

Inspiratory muscle training (IMT) with inspiratory threshold‐loading devices (threshold‐IMT) increases respiratory muscle strength and endurance, which in turn improves respiratory volume and sputum clearance and reduces postoperative pulmonary complications (McCann 2019).

Body mass index (BMI) is an important predictor of postoperative complications; both a low BMI (below 18.5 kg/m²) and a very high BMI (40 kg/m² or higher) increase the risk of in‐hospital mortality (Mariscalco 2017). Consequently, ensuring BMI is in the optimal range and reversing malnutrition, sarcopenia, and frailty may improve physiological reserves required to deal with the surgical stress response.

The preoperative period is also suitable for targeted lifestyle modifications such as smoking and alcohol cessation. Amongst people undergoing cardiac surgery, smoking is associated with higher postoperative morbidity, including higher rates of respiratory infections and longer stays in the intensive care unit (ICU), as well as higher inpatient mortality (14.8% in current smokers versus 2.1% in never‐smokers, P < 0.001; Jones 2011). Similarly, heavy alcohol consumption has been associated with increased postoperative mortality in people undergoing CABG (Grabas 2016).

In addition, people undergoing cardiac surgery frequently experience mental health problems, which can be exacerbated by poor cardiovascular fitness and inability to exercise. Amongst people with coronary artery disease, an estimated 31% to 45% experience depressive symptoms (Huffman 2013), and an estimated 32% experience anxiety (Easton 2016). Studies have found that preoperative depression and anxiety are associated with increased risk of postoperative mortality in people undergoing cardiac surgery (Takagi 2017).

Why it is important to do this review

People who undergo cardiac surgery have a high risk of postoperative complications, which can lead to reduced quality of life in the short and long term, representing a significant cost for the UK National Health Service (NHS). Prehabilitation has been widely implemented in various surgical pathways in the UK since the early 2010s, but not in cardiac surgery (Prehabilitation for People with Cancer).

Cardiac surgery is unique in that it encompasses two different pathways (urgent and elective) and is associated with a number of complications not present in other types of surgery. The ability to exercise – the cornerstone of prehabilitation – is compromised in many of these people before surgery. For example, it is not known whether an exercise‐based intervention can be delivered safely in people with severe symptomatic aortic stenosis.

Consequently, there is a need to consider both traditional prehabilitation interventions (which may need to be modified for this population) and other cardiac surgery‐specific interventions not included in prehabilitation programmes for other types of surgery (e.g. interventions to prevent neurological complications such as delirium; Humeidan 2021).

A consensus guideline for the optimal perioperative management of people undergoing cardiac surgery recommends preoperative exercise, correction of nutritional deficiency, improvement of glycaemic control before surgery, and engagement and education tools (especially through online/digital platforms) as preoperative strategies to improve outcomes after surgery (Engelman 2019). The guideline highlights the lack of evidence for preoperative optimisation and does not recommend a specific preoperative optimisation programme.

There is one previous Cochrane review of preoperative exercise in cardiac surgery (Hulzebos 2012). However, it focusses on one type of prehabilitation and was published in 2012. Since then, several randomised controlled trials (RCTs) have investigated the role of single‐component and multimodal prehabilitation programmes in people undergoing cardiac surgery, and further systematic reviews have incorporated some of these trials (Kehler 2017; Marmelo 2018). These reviews have focused mainly on exercise interventions over other types of prehabilitation. Consequently, it is important to conduct a systematic review summarising the evidence for all types of prehabilitation interventions. We hope that the evidence will be useful for creating a preoperative optimisation programme for people undergoing cardiac surgery.

Objectives

The overarching aim of this review is to determine the benefits and harms of prehabilitation on postoperative outcomes in people undergoing cardiac surgery. The specific objectives are:

• to identify and describe all prehabilitation interventions that have been administered prior to cardiac surgery (urgent and elective pathways);

• to compare the effectiveness of the different interventions against no intervention or usual care on postoperative and long‐term outcomes (general and cardiac surgery‐specific); and

• to identify the harms associated with prehabilitation interventions.

Methods

Criteria for considering studies for this review

Types of studies

We will include all published and unpublished RCTs (excluding quasi‐RCTs), irrespective of publication date or language.

Types of participants

Adults (aged 18 years and older) scheduled to undergo cardiac surgery (CABG surgery, heart valve surgery, thoracic aortic surgery) on the elective or the urgent pathway will be eligible for inclusion in this review. We will exclude people undergoing a heart transplant, because they differ from people undergoing standard cardiac surgery procedures in terms of demography, comorbidities, and ability to participate in standard prehabilitation programmes. For studies which include only a subset of eligible participants, we will include the study if more than 80% of participants are undergoing cardiac surgery.

Types of interventions

We will include all types of prehabilitation interventions, including the following.

1. Physical activity (any form of exercise, e.g. endurance, aerobic, low‐impact, high‐intensity interval training)

2. Respiratory interventions (e.g. inspiratory muscle training, incentive spirometry, chest physiotherapy, pulmonary rehabilitation, any type of breathing exercises)

3. Nutritional interventions (e.g. calorie restriction, high‐energy diet, single/multiple nutrient supplementation, oral nutritional supplements, immunonutrition)

4. Psychological interventions (e.g. to improve psychological well‐being, address behavioural change, address anxiety caused by the disease process or impending surgery)

5. Lifestyle modification interventions (e.g. smoking and alcohol cessation)

6. Educational interventions (to improve people's understanding of their condition, the surgery and recovery process, and the importance of lifestyle modification)

7. Any combination of the above interventions

We will include all studies that compare one of these interventions (or more than one in multiarm trials) with no intervention or usual care (which may involve some form of lifestyle guidance or low intensity support). We will not include studies that compare different prehabilitation interventions head to head.

We will include interventions administered at home, in community settings, or in hospital, provided they are administered before surgery. We will not include interventions administered on the day of the operation, as these are normally aimed at optimising the anaesthetic regimen or pain control, both of which are outside the scope of this review.

We will include studies in which interventions continued postoperatively, provided they began preoperatively.

We will not include trials that evaluate pharmacological/procedural interventions administered preoperatively to reduce cardiac surgery‐specific complications. There are numerous RCTs of pharmacological interventions (e.g. direct oral anticoagulants, amiodarone, corticosteroids, and statins for prevention of atrial fibrillation; pharmacological interventions for the prevention of renal injury; organ protection interventions targeting the inflammatory response) and procedural interventions (e.g. remote ischaemic preconditioning for preventing acute kidney injury), and previous meta‐analyses and network meta‐analyses have synthesised the evidence on these interventions (Abbasciano 2020; Abbasciano 2021; Liu 2021; Pathak 2021; Roman 2021; Thein 2018; Wang 2017).

Nor will we include pharmacological/procedural interventions administered preoperatively to optimise non‐cardiac comorbidities. Optimisation of comorbidities (e.g. chronic obstructive pulmonary disease, heart failure, diabetes, anaemia) through medication or procedures is another essential part of preoperative care that may improve postoperative outcomes; however, it is not conventionally considered a component of prehabilitation. We will only consider including such interventions if they form part of a multimodal prehabilitation programme.

Types of outcome measures

We will seek to collect the following primary and secondary outcome measures, but we will not exclude studies based on reported outcomes.

Primary outcomes

1. All‐cause mortality

2. Health‐related quality of life (HRQoL), measured with a validated instrument (e.g. the 36‐item Short‐Form Health Survey (SF‐36) or EuroQol Five‐Dimension Questionnaire (ED‐5D); Pequeno 2020)

We will collect data reported in the perioperative period (up to hospital discharge and within 30 days of surgery) and at long‐term follow‐up (from surgery up to one year or later if data are available).

Secondary outcomes

1. Hospital readmission (within one year after surgery)

2. Length of hospital stay

3. Length of ICU stay

4. Postoperative pulmonary complications, including pneumonia and prolonged ventilation

5. Postoperative heart‐related complications (arrhythmia, including atrial fibrillation; myocardial infarction; pacemaker/implantable cardioverter‐defibrillator (ICD) insertion; heart failure).

6. Postoperative neurological complications (seizures, delirium, stroke)

7. Postoperative wound infection

8. Acute kidney injury/renal failure

9. Gut complications/infections

10. Blood loss/use of blood products

11. Pain (acute, measured using a numerical rating scale or a visual analogue scale; chronic, measured using a validated instrument such as the Brief Pain Inventory; Breivik 2008)

12. Activities of daily living (ADLs, measured using a validated instrument such as the Katz Index of Independence in Activities of Daily Living or the Lawton Instrumental Activities of Daily Living (IADLs) Scale; Edemekong 2022)

13. Any adverse events that occur during the intervention (before surgery). These may be minor (e.g. breathlessness or muscle pains resulting from exercise), moderate (e.g. chest pain), or severe (e.g. death). Adverse events that occur after surgery will likely be related to the surgery or the underlying disease and will be captured as part of the primary and secondary clinical outcomes.

We will extract data up to the longest follow‐up reported in individual studies but will only combine data for similar time points. For pulmonary complications, heart‐related complications, and neurological complications, we will extract data on each component of these complications, if available, and combine data only for components that are similar. While heart and neurological complications are normally reported as individual complications, pulmonary complications are frequently reported as a composite, although the components may vary. We will combine data on pulmonary complications reported as a composite because this is the common way of reporting them. We will also extract data on all individual components (e.g. pneumonia) and combine these if sufficient studies provide such data.

Blood loss/use of blood products may be reported as a dichotomous outcome (yes/no) or as a continuous outcome (e.g. mL of blood lost, units of blood transfused). We will extract all data as reported and combine dichotomous and continuous data separately if sufficient data are available.

Any outcome that may occur more than once in the same individual will be counted once (i.e. the number of participants with at least one event).

Search methods for identification of studies

Electronic searches

We will search the following electronic databases using relevant keywords, subject headings (controlled vocabularies), and search syntax. We will not restrict the search by date, language, or publication status.

1. Cochrane Central Register of Controlled Trials (CENTRAL; current issue) in the Cochrane Library

2. MEDLINE ALL Ovid (1946 to date of search; Appendix 1)

3. Embase Ovid (1974 to date of search)

4. PsycINFO Ovid (1806 to date of search)

5. Web of Science: Science Citation Index Expanded (SCI‐EXPANDED; 1900 to date of search)

6. Web of Science: Conference Proceedings Citation Index‐Science (CPCI‐S; 1990 to date of search)

We will search the following trial registers for ongoing or unpublished trials.

1. US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov)

2. World Health Organization (WHO) International Clinical Trials Registry Platform (trialsearch.who.int)

Searching other resources

We will screen the reference lists of all included studies and relevant systematic reviews.

We will search for systematic reviews and health technology assessments in MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews in the Cochrane Library, and the International health technology assessments database (INAHTA).

We will also run a pragmatic search for grey literature in the following sources.

1. Open Grey (www.opengrey.eu)

2. ProQuest Dissertations & Theses Global (www.proquest.com/products-services/pqdtglobal.html)

3. DART‐Europe E‐theses Portal (www.dart-europe.org)

4. British Libraries e‐theses online service (EThOS; ethos.bl.uk)

5. Networked Digital Library of Theses and Dissertations (NDLTD; search.ndltd.org/)

6. Open Access Theses and Dissertations (oatd.org)

We will contact experts in the field and trial authors for further information or unpublished data.

Data collection and analysis

Selection of studies

Two review authors will independently screen titles and abstracts of the records returned by the search to exclude those that are clearly ineligible. We will retrieve the full‐text articles of all remaining records, and two review authors will independently assess them against our eligibility criteria, recording all reasons for exclusion at this stage. We will resolve any disagreements through discussion with a third review author. We will present the study selection process in a PRISMA flow diagram.

Data extraction and management

Two review authors will independently extract the following data from each included study, resolving any disagreements through discussion with a third review author. We will develop and pilot a data extraction form for this review.

1. Publication details (authors, title, date of publication, country of origin, language if not published in English, funding source, authors' conflicts of interest)

2. Study characteristics (setting, study design, number of participants randomised to each group, whether intention‐to‐treat analysis was applied)

3. Participant characteristics (demographics, inclusion and exclusion criteria, comorbidities)

4. Procedure characteristics (CABG, valve surgery, combined CABG and valve surgery, elective or urgent pathway)

5. Intervention and comparator (these will be intervention‐specific, but for all interventions we will extract: mode of delivery; place of delivery; who delivered the intervention and whether they underwent specific training; standardisation of intervention delivery; duration of intervention, including number and duration of sessions; format of delivery (individual or group); intervention adherence (how was it encouraged and monitored); theoretical rationale for how the intervention improves postoperative outcomes)

6. Outcomes (as detailed in the previous section). We will record the number of participants assessed for each outcome, the mean values and standard deviations (SDs) for continuous data (or medians and interquartile ranges if mean values and SDs are unavailable), the number of events in each group for categorical data, and any reported summary statistics (e.g. effect estimates, confidence intervals (CIs), standard errors (SEs), ranges).

We will contact the trial authors for information if any of the above data items are missing.

Where multiple publications of the same study have reported different outcomes, we will extract all relevant outcome data from the different publications. Studies reported in languages other than English will be translated.

Assessment of risk of bias in included studies

We will assess risk of bias for the outcomes all‐cause mortality, HRQoL, hospital readmission, length of hospital stay, and adverse events. At least two review authors (RP and MP) will independently assess risk of bias in the effect of assignment to the intervention. Disagreements will be resolved in conjunction with a third review author. We will use the Cochrane risk of bias tool (RoB 2), using all the signalling questions, to determine the overall risk of bias for different outcomes in each trial (low risk of bias, high risk of bias, or some concerns) based on the following domains (Higgins 2023).

1. Risk of bias arising from the randomisation process

2. Risk of bias due to deviations from the intended interventions (effects of assignment to intervention and effect of adhering to intervention)

3. Risk of bias due to missing outcome data

4. Risk of bias in measurement of the outcome

5. Risk of bias in selection of the reported result

We are unaware of any cluster trials of prehabilitation interventions, but if we identify any, we will use the variant of RoB 2 for cluster‐randomised trials.

Measures of treatment effect

We will calculate pooled risk ratios (RRs) and 95% CIs for dichotomous outcomes (e.g. mortality, morbidity, hospital readmission, adverse events, postoperative complications). For continuous outcomes (most participant‐reported outcomes, physiological and clinical parameters), we will calculate pooled mean differences (MDs) and 95% CIs when results are reported on the same scale (or can be converted to the same scale), or standardised mean differences (SMDs) with 95% CIs when results are reported on different scales. If studies do not report mean values and SDs, we will derive these from the reported test statistics (e.g. SDs from SEs or 95% CIs) or estimate them from other summary statistics (e.g. mean and SD from median and range). Some studies may report means but not SDs; in this case, we will estimate SDs from the mean of the SDs reported in similar studies (assessing a similar intervention) within that treatment arm. If no appropriate data are available, we will report the outcome narratively.

Unit of analysis issues

We are unaware of any cluster‐randomised trials of prehabilitation in any surgical population. Cross‐over trials are not feasible in the context of surgery. We therefore expect that we will only identify individually randomised, parallel‐group trials.

Where trials include multiple intervention groups and a single control group, we will only use data from the intervention groups that meet our inclusion criteria. If we include two or more intervention groups in the same meta‐analysis, we will divide the number randomised to the control group by the number of intervention groups, but we will keep the means and SDs for the control group the same.

Any outcome that may occur more than once in the same individual will be counted once (i.e. the number of participants with at least one event).

If a study reports outcome measurements at more than one time point, we will extract data up to the longest follow‐up but will only combine outcomes reported at similar time points (e.g. in hospital, up to 30 days, six months, and 12 months).

Dealing with missing data

If data are missing from study publications, we will first attempt to back‐calculate from data presented (e.g. numerator or denominator from percentages; SD from SE or 95% CI). If this is not possible, we will attempt to contact the study authors to request the missing data. Studies assessing lifestyle interventions may have issues with adherence, so we will carefully report reasons for missing data (e.g. dropouts, losses to follow‐up, withdrawals).

Assessment of heterogeneity

We will examine and report variability in study design and risk of bias (methodological heterogeneity) and characteristics of participants, baseline data, interventions, and outcomes (clinical heterogeneity). To assess statistical heterogeneity, we will visually inspect forest plots and calculate the I² statistic (Deeks 2022). We will apply the following thresholds to interpret I² values.

1. 0% to 40%: might not be important.

2. 30% to 60%: may represent moderate heterogeneity.

3. 50% to 90%: may represent substantial heterogeneity.

4. 75% to 100%: represents considerable heterogeneity.

We will seek to describe and explore any observed statistical heterogeneity in the results of the review.

Assessment of reporting biases

If we include 10 or more studies in a meta‐analysis, we will use funnel plots and the Egger test to examine small study bias (Egger 1997).

Data synthesis

As prehabilitation includes multiple components (e.g. physical activity, respiratory interventions, nutritional interventions) administered alone or in combination, we will only pool data when interventions are deemed sufficiently similar to justify pooling. However, even with similar interventions, there is likely to be substantial heterogeneity in the interventions and their delivery. Given this likely clinical heterogeneity, we will use random‐effects meta‐analysis models for our primary analysis to pool data across trials. However, since random‐effects models give relatively greater weight to small studies (which may be at higher risk of bias), we will undertake a sensitivity analysis by repeating all analyses with statistically significant results using a fixed‐effect model. If the included trials are not sufficiently similar to justify meta‐analysis, we will summarise the findings in narrative format, following the Synthesis Without Meta‐analysis (SWiM) guideline (Campbell 2020). We will perform the data synthesis using Review Manager Web (RevMan Web 2022) and STATA (StataCorp 2020).

Subgroup analysis and investigation of heterogeneity

If sufficient data are available for any of the primary or secondary outcomes, we will attempt to perform the following subgroup analyses using either stratified meta‐analysis or meta‐regression.

1. Type of surgery: CABG versus valve versus both (different underlying pathology and risk factors)

2. Intervention pathway: urgent versus elective (higher risk of certain complications after surgery in people who have urgent surgery)

3. Type of prehabilitation: single component (e.g. physical activity) versus multimodal (potential for synergistic effect of multiple components on postoperative outcomes)

4. For interventions including physical activity or breathing exercises, dose of exercise (calculated as number of weeks of exercise training × average number of sessions/week × average duration of session in minutes) subgroups will be defined as above and below the median. A higher dose of exercise results in higher cardiorespiratory fitness, which may be associated with better outcomes after surgery.

We will use the formal test for subgroup interactions in Review Manager to investigate subgroup effects, interpreting the results with caution (RevMan Web 2022). We will compare the magnitude of the effects between subgroups by investigating the overlap of the CIs of each point estimate, with non‐overlap indicating statistical significance.

Sensitivity analysis

We will conduct the following sensitivity analyses for any of the outcomes that have sufficient data to combine in a meta‐analysis.

1. Including only trials classified as being at low overall risk of bias

2. Excluding trials with more than 20% dropout rate to assess the impact of missing data on results and conclusions

3. Including only trials with 100 participants or more

4. Including only published trials (not abstracts)

5. Conducting fixed‐effect meta‐analyses where the random‐effects model obtained statistically significant results

Summary of findings and assessment of the certainty of the evidence

We will use GRADEpro software to assess the certainty of evidence for the outcomes specified below (GRADEpro GDT). We will downgrade the evidence from high certainty by one or two levels for each of the following domains (Balshem 2011).

1. Indirectness of evidence

2. Unexplained heterogeneity

3. Publication bias

4. Risk of bias due to study design limitations (we will consider our RoB 2 judgements when deciding whether to downgrade the result for risk of bias)

5. Imprecision of results

We will create a separate summary of findings table for each comparison (for all time points at which data could be combined) including the following outcomes.

1. All‐cause mortality

2. HRQoL

3. Hospital readmission

4. Length of hospital stay

5. Adverse events that occur during the intervention

Two review authors (RP and MP) will conduct the GRADE assessments independently. A third review author will moderate any disagreements.

What's new

Date	Event	Description
1 February 2024	Amended	Amendment to fix formatting issues.

History

Protocol first published: Issue 1, 2024

Appendices

Appendix 1. Preliminary MEDLINE (Ovid) search strategy

Ovid MEDLINE(R) ALL <1946 to December 01, 2021>

1 exp Cardiovascular Surgical Procedures/ 422790

2 Cardiopulmonary Bypass/ 24475

3 ((thorax or thoracic) adj3 (operation? or elective? or surgery or surgeries or surgical)).mp. 41140

4 ((cardiac or cardio* or coronary or heart or epicardi* or myocardi* or pericardi* or transmyocardi*) adj3 (bypass* or graft* or graR* or operation? or elective? or surgery or surgeries or surgical or procedure? or intervention? or implant* or prosthe* or transplant* or replacement? or repair* or revasculari?ation or re‐vasculari?ation)).mp. 388402

5 (CBG or CABG).tw,kf. 21424

6 (cardiomyoplast* or arterial switch operation? or maze procedure? or norwood procedure? or pericardiectom* or pericardiocentes* or pericardiotom*).mp. 10356

7 (pacemaker? or pace maker? or implant* cardio* defib*).mp. 62663

8 (ventricular assist device or VAD or LVAD or artificial heart).mp. 22516

9 exp Heart Valves/su [Surgery] 37143

10 ((cardi* or heart* or aortic* or mitral* or pulmonary or tricuspid) adj5 valv* adj5 (bypass or plasty or graft* or graR* or operat* or elective or surgery or surgeries or surgical or procedure? or intervention? or implant* or prosthe* or transplant* or replac* or repair* or revasc* or re‐vasc*)).mp. 88721

11 ((saphenous vein or radial artery) adj3 harvest*).mp. 853

12 or/1‐11 685985

13 (pre‐hab* or prehab*).mp. 1082

14 ((presurg* or pre‐surg* or preoperati* or pre‐operati*) adj3 (conditioning or optimis* or optimiz* or rehab* or re‐hab* or care)).mp. 67193

15 (pre adj2 (postsurg* or post‐surger* or postoperati* or post‐operati*) adj3 (conditioning or optimis* or optimiz* or rehab* or re‐hab* or care)).tw,kf. 722

16 ((before or prior to) adj3 (CBG or CABG or bypass* or graft* or graR* or operation? or elective or surgery or surgeries or surgical or procedure? or intervention? or angioplast* or atherectom* or implant* or prosthe* or transplant* or replacement? or repair* or revasculari?ation or re‐vasculari?ation) adj12 (conditioning or optimis$ or optimiz$ or rehab$ or re‐hab$ or care)).tw,kf. 4159

17 preoperative exercise/ 163

18 Preoperative Care/mt, rh [Methods, Rehabilitation] 15826

19 (preoperative care/ or preoperative period/) and (conditioning or optimis* or optimiz* or rehab* or re‐hab*).tw,kf. 2606

20 Postoperative Complications/pc and ((presurg* or pre‐surg* or preoperati* or pre‐operati*) adj3 (assess* or intervention*)).tw,kf. 593

21 or/13‐20 72495

22 12 and 21 9106

23 preoperative care/ or preoperative period/ or *perioperative care/ 81646

24 (presurg* or pre‐surg* or preoperati* or pre‐operati*).tw,kf. or (perioperat** or peri‐operati*).ti,kf. 391615

25 (pre adj2 (postsurg* or post‐surg* or postoperati* or post‐operati*)).tw,kf. 27641

26 ((before or prior to) adj3 (CBG or CABG or bypass or plasty or graft* or graR* or operati* or elective or surgery or surgeries or surgical or procedure? or intervention? or implant* or prosthe* or transplant* or replac* or repair* or revasc* or re‐vasc*)).tw,kf. 193755

27 (prevent* adj3 complications adj3 surgery).tw,kf. 587

28 (((elective or scheduled or prescheduled) adj5 (bypass* or graft* or graR* or operation? or surgery or surgeries or surgical or procedure? or intervention? or implant* or prosthe* or transplant* or replacement? or repair* or revasculari?ation or re‐vasculari?ation)) and (reduc* or prevent*)).tw. and (((post* adj3 complications) or (adverse adj (effect? or event? or outcome?))).mp. or adverse effects.fs.) 6933

29 or/23‐28 587176

30 exp Exercise/ or exp Exercise Therapy/ 256830

31 physical therapy modalities/ 38830

32 physical fitness/ 28629

33 (exercis* or aerobics or swimming or hydrotherap* or preconditioning or pre‐conditioning or physical fitness or physical activit* or physiotherap* or physical therap*).mp. 615430

34 physical conditioning.mp. 18559

35 high intensity interval training.mp. 2892

36 ((muscle or endurance or resistance or weight or strength) adj2 training).mp. 29490

37 ((inspiratory or respiratory) adj2 training).mp. 1648

38 pulmonary rehab*.mp. 4320

39 (isch?emic adj (preconditioning or pre‐conditioning)).mp. 10436

40 (positive pressure adj (breathing or respiration)).mp. 18726

41 ((function or functional capacity or functional recovery) adj2 (enhanc* or improv* or maximi*)).tw,kf. 73944

42 Nutrition Therapy/ or exp diet therapy/ or exp diet/ or eating/ or nutritional physiological phenomena/ or elder nutritional physiological phenomena/ or nutritional requirements/ or nutritional status/ 422521

43 exp Dietary Supplements/ or exp Food, Fortified/ 97432

44 (pharmaconutri* or pharmaco‐nutri*).mp. 184

45 exp antioxidants/ad, tu, th [Administration & Dosage, Therapeutic Use, Therapy] 73089

46 ((antioxida* or anti‐oxida* or provitamin* or acetylcysteine or (acetyl adj2 cysteine) or NAC or allopurinol or ascorbic acid or ascorbate or dehydroascorb* or vitamin c or caroten* or coenzyme Q* or co‐enzyme Q* or ubiquinone or flavan* or flavon* or ginko* or melatonin or methion* or selenium or (superoxide adj2 dismutase) or SOD or tocopherol* or tocotrienol or vitamin E) adj3 (supplement* or therap* or presurg* or pre‐surg* or preoperati* or pre‐operati*)).tw,kf. 26284

47 exp Amino Acids/ad, tu, th 96258

48 ((amino acid? or arginine or histidine or isoleucine or leucine or lysine or methionine or phenylalanine or threonine or tryptophan or valine) adj3 (supplement* or therap* or presurg* or pre‐surg* or preoperati* or pre‐operati*)).tw,kf. 8712

49 Glutamine/ad, th, tu 1926

50 ((glutamim* or Lglutamin* or GLN) adj3 (supplement* or therap* or presurg* or pre‐surg* or preoperati* or pre‐operati*)).tw,kf. 391

51 fish oils/ or cod liver oil/ or fatty acids, omega‐3/ or docosahexaenoic acids/ad, tu, th or eicosapentaenoic acid/ad, tu, th or alpha‐linolenic acid/ad, tu, th 24314

52 ((omega3 or omega‐3 or PUFA or n‐3PUFA* or n3PUFA* or ((n3 or n‐3 or w3 or w‐3) adj3 (fatty acid? or polyunsaturat* or oil)) or cod liver oil? or fish oil? or DHA or docosahex* or eicosapent* or EPA or ethyl‐eicosapent* or ethyleicosapent* or alphalinolen* or alpha‐linolen* or linolenate* or linolenic*) and (supplement* or therap* or presurg* or pre‐surg* or preoperati* or pre‐operati*)).tw,kf. 19961

53 exp Malnutrition/dh, pc, rh, th [Diet Therapy, Prevention & Control, Rehabilitation, Therapy] 17352

54 (diet$ or nutrition$ or malnutrition or underweight or low BMI or undernourish$ or undernutrition or malnourish$ or immunonutrition or macronutrient$ or micronutrient$ or immuno‐nutrition or macro‐nutrient$ or micro‐nutrient$).tw,kf. 903485

55 (carbohydrate adj (loading or preload* or pre‐load*)).mp. 598

56 calorie restriction?.mp. 3151

57 ((oral or food or multinutrient* or multi‐nutrient* or multivitamin* or iron or protein or folate or folic acid or thiamine or vitamin*) adj3 supplement*).mp. 57290

58 ((iron or protein or folate or thiamine or vitamin*) adj3 (deficient or deficienc*)).mp. 102049

59 ((fortif$ or enrich$) adj3 (food$ or feed$)).mp. 13677

60 (weight adj2 (loss or lose$ or lost or losing or watch*) adj2 (program$ or plan$ or procedure?)).mp. 3455

61 (fortisip or complan).tw,kf. 20

62 Adaptation, Psychological/ 100026

63 Cognitive Therapy/ or Psychotherapy/ or exp Mind‐body therapies/ or behavior therapy/ or mindfulness/ 161095

64 (psychotherap* or counselling or counseling).mp. 222345

65 (mindfulness or mind train*).mp. 10404

66 (CBT or ((cognitive or talking or mental health or behavi*) adj3 (intervention* or therap*))).mp. 105935

67 ((education$ or psychological or psychosocial or behavio?ral or cognitive) adj3 (intervention$ or program$)).mp. 124942

68 (psychoeducat* or psychoeducat*).mp. 6018

69 ((anxiety or stress or fear) adj2 (manag$ or strateg$ or therap$ or reduc$)).mp. 49316

70 ((selfcare or self‐care or self‐help or coping) adj2 (mechanism$ or strateg$ or behavio?r$)).mp. 25545

71 Smoking Cessation/ 30907

72 ((smoking or drug$) adj2 (cessation or stop$ or quit$ or giving up or give up)).tw,kf. 38541

73 nicotine replacement therap*.mp. or NRT.tw,kf. 4153

74 (reduc* adj2 (alcohol or drinking behavi*)).tw,kf. 7224

75 (complex intervention or ((co‐ordinated or comprehensive or factorial or interdisciplinary or inter‐disciplinary or multiple or "multi component?" or multicomponent? or multidisciplin* or "multi disciplin*" or multidimension* or "multi dimension*" or multifactor* or "multi factor*" or multifacet* or "multi facet*" or multilevel* or "multi level*" or multimodal* or "multi modal*" or multiparamet* or "multi paramet*") adj3 (intervention? or program* or project? or strateg* or study or support* or system? or therap* or train* or trial))).tw,kf. 174046

76 or/30‐75 2678735

77 29 and 76 55119

78 12 and 77 7206

79 22 or 78 15044

80 controlled clinical trial.pt. 94570

81 randomized controlled trial.pt. 552234

82 clinical trials as topic/ 198268

83 (randomi#ed or randomi#ation or randomi#ing).ti,ab,kf. 718336

84 (RCT or "at random" or (random* adj3 (administ* or allocat* or assign* or class* or cluster or crossover or cross‐over or control* or determine* or divide* or division or distribut* or expose* or fashion or number* or place* or pragmatic or quasi or recruit* or split or subsitut* or treat*))).ti,ab,kf. 636175

85 placebo.ab,ti,kf. 229891

86 (control* adj3 group*).ab. 595090

87 ((single or double or triple or treble) adj2 (blind* or mask* or dummy)).ti,ab,kf. 185828

88 double‐blind method/ or random allocation/ or single‐blind method/ 294813

89 trial.ti. or (control* and trial).ab,kf. 428925

90 or/80‐89 1918728

91 exp animals/ not humans.sh. 4923981

92 (exp Animals, Laboratory/ or exp Animal Experimentation/ or exp Models, Animal/) not humans.sh. 1035882

93 90 not (91 or 92) 1665060

94 79 and 93 2660

95 comment/ or case report/ or exp historical article/ or news/ 3742049

96 (exp child/ or exp infant/) not adult/ 1830701

97 ((child* or infant* or newborn* or neonat*) not adult*).ti. 1121349

98 94 not (95 or 96 or 97) 2497

Contributions of authors

MP: conceived the study, provided prehabilitation expertise and edited the protocol for intellectual content.
RP: provided systematic review expertise and edited the manuscript.
NS: wrote the first draft of the manuscript.
CA: provided nutritional prehabilitation expertise and edited the manuscript.
RT: provided expertise on complex lifestyle interventions in populations with cardiovascular disease and edited the manuscript.
JC: provided cardiology and heart failure expertise and edited the manuscript.
EA: provided cardiac surgery and prehabilitation in cardiac surgery expertise and edited the manuscript.
BG: provided preoperative assessment/cardiac anaesthesia expertise and edited the manuscript.
GM: provided cardiac surgery expertise and edited the manuscript.
AM: provided statistical expertise and edited the manuscript.
PC: provided the patient perspective and edited the manuscript.
SD: designed and conducted the literature searches.
DL: provided critical care and prehabilitation expertise and edited the manuscript.
MG: provided prehabilitation expertise and edited the manuscript.

Sources of support

Internal sources

• New Source of support, UK

  This review is funded by the NIHR [Programme Development Grant (NIHR203304)]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

External sources

• NIHR, UK

  This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Heart Group. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, the National Health Service (NHS), or the Department of Health and Social Care.

Declarations of interest

MP: none
RP: none
NS: anaesthesia trainee at Imperial College Healthcare NHS Trust
CA: none
RT: none
JC: received institutional grants from Pharmacosmos Therapeutics Inc. and Vifor Pharma. Member of the European Society of Cardiology, American College of Cardiology, American Heart Association, British Society for Heart Failure, and Heart Failure Society of America.
EA: cardiac surgeon at the South Tees NHS Foundation Trust. Conducted the Heart Research UK‐funded PREPs trial of a prehabilitation intervention in cardiac surgery, which is eligible for inclusion in this review.
BG: cardiac anaesthetist and intensive care doctor for University Hospitals Bristol and Weston NHS Foundation Trust.
GM: cardiac surgeon, University Hospitals Leicester. Received institutional grants from the British Heart Foundation (BHF) and the National Institute for Health And Care Research (NIHR).
AM: none
PC: none
SD: Cochrane Information Specialist (Common Mental Disorders Group)
DL: Consultant in Critical Care and Perioperative Medicine. Received an institutional grant from the National Institute of Health. President of the International Prehabilitation Society and member of Perioperative Exercise Testing and Training Society. Promotes prehabilitation in general surgery. Uses social media (X, formerly Twitter) to tweet about prehabilitation studies in general surgery. 
MG: Consultant in Critical Care Medicine at University Hospital Southampton NHS Foundation Trust. Received personal funds from AstraZeneca, Edwards Lifesciences, South West Sensor Ltd and Spire Healthcare Ltd. Received institutional grants from Edwards Lifesciences and Sphere Medical. Is a Council Member of Royal College of Anaesthetists and Deputy Chair of the UK Centre for Perioperative Care. Has a research interest in, and is an advocate for, prehabilitation, particularly in relation to cancer. Developed a clinical prehabilitation service for cancer patients at the University Hospital Southampton NHS Foundation Trust (no personal financial interest).

Edited (no change to conclusions)