Pre-operative Rehabilitation for Reduction of Hospitalization After Coronary Bypass and Valvular Surgery.
Phase: NA
Conditions: Patients Waiting for Coronary Artery Bypass Graft Surgery, Patients Waiting for Aortic Valve Repair or Replacement, Patients Waiting for Mitral Valve Repair or Replacement, Patients Waiting for Combined Procedures. (CAGB and Valve)
Sponsor: St. Boniface Hospital

  
 
 
 
THE PREHAB STUDY 
CLINICAL STUDY PROTOCOL 
The PREHAB Study - Pre-operative Rehabilitation for reduction of Hospitalization After coronary 
Bypass and valvular surgery.  A three center prospective, randomized, open, blinded endpoint 
(PROBE) controlled trial using assessor blinding and intention-to-treat analysis. 

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Study Synopsis 
Title: 
The PREHAB Study - Pre-operative Rehabilitation for reduction of Hospitalization 
After coronary Bypass and valvular surgery. 
Principal 
Investigator: 
Dr. Rakesh Arora 
Email:  rarora@sbgh.mb.ca 
Work Phone: (204) 258-1031 
 
Work Fax:(204) 231-4624 
Institution: St. Boniface Hospital/University of Manitoba 
Department: Cardiac Sciences/Surgery 
CR3012-I.H. Asper Institute, St. Boniface Hospital 
369 Tache Ave., Winnipeg, MB, R2H2A6 
Co-investigators: 
Dr. Todd Duhamel 
204-474-8922 
tduhamel@sbrc.ca 
 
Faculty of Kinesiology and Recreation Management University of 
Manitoba & Institute of Cardiovascular Sciences, St. Boniface Hospital. 
Dr. Ansar Hassan 
506-648-6102 
ahassan@dal.ca 
 
New Brunswick Heart Centre -Saint John Regional Hospital 
Dr. Nicholas Giacomantonio 
902-473-3815 
Nicholas.Giacomantonio@ 
cdha.nshealth.ca 
 
Dalhousie University - Queen Elizabeth II Health Sciences Centre Halifax 
Infirmary Site 
Dr. Navdeep Tangri 
204-336-5716 
ntangri@sogh.mb.ca 
 
Seven Oaks Hospital/University of Manitoba 
Dr. Thang Ngoc Nguyen 
204-258-1317 
tnguyen1@sbgh.mb.ca 
 
St. Boniface Hospital/University of Manitoba Section of Cardiology 
Cardiac Rehabilitation and Prevention Lipoprotein Disorder Clinic, St. 
Boniface Hospital, Winnipeg 
Dr. Sarvesh Logsetty 
204-787-7638 
logsetty@cc.umanitoba.ca 
 
Health Sciences Centre/University of Manitoba 
Dr. Jitender Sareen 
204-787-7078 
sareen@cc.umanitoba.ca 
 
Health Sciences Centre/University of Manitoba 
Dr. Colleen Metge 
204-926-7127 
cmetge@wrha.mb.ca 
 
Winnipeg Regional Health Authority 
Dr. Hilary Grocott 
204-258-1313 
hgrocott@sbgh.mb.ca 
 
St. Boniface Hospital/University of Manitoba 
Dr. Jo Anne Sawatzky 
204-474-9317 
joanne.sawatzky@ 
ad.umanitoba.ca 
 
Faculty of Nursing – University of Manitoba 
Dr. Kenneth Rockwood 
902-473-8687 
Kenneth.Rockwood@ 
cdha.nshealth.ca 
 
QEII HSC/Dalhousie University 
Dr. Sean Bagshaw 
780-407-6755 
bagshaw@ualberta.ca 
 
University of Alberta 
Dr. Jonathan Afilalo 
514-340- 8222 
Ext. 6842 
jonathan.afilalo@mcgill.ca 
 
McGill University 
Dr. Jean-Francois Legare 
902-473-7597 
jean.legare@cdha.nshealth.ca 

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 
QEII HSC/Dalhousie University 
 
Dr. Yoan Lamarche         514- 376-3330 
                                            Ext. 3715 
yoanlamarche@gmail.com 
 
 
Montreal Heart Institute 
 
Dr. Francois Dagenaise         418- 656-
8711 (3797) 
 
francois.dagenais@chg.ulaval.ca 
 
 
Quebec heart and Lung institute (University of Laval) 
Study Sites (with 
site lead contact 
information): 
St. Boniface General Hospital 
Dr. Rakesh Arora/Dr. Todd Duhamel 
CR3012-I.H. Asper Institute 
369 Tache Ave., Winnipeg, MB, R2H2A6 
Phone: (204) 258-1031  
Fax: (204) 231-4624 
Email: rarora@sbgh.mb.ca 
Saint John Regional Hospital - New Brunswick Heart Centre 
Dr. Ansar Hassan 
400 University Avenue 
PO Box 2100 Saint John, NB, E2L 4L2 
Phone: (506) 648-6102 
Email: ahassan@dal.ca 
Queen Elizabeth II Health Sciences Centre 
Dr. Nicholas Giacomantonio 
1796 Summer Street, 2nd Floor, Room #2132 
Halifax, Nova Scotia B3H 3A7 
Phone: (902) 473-3815 
Fax: (902) 473-7277 
Email: Nicholas.Giacomantonio@cdha.nshealth.ca 
Montreal Heart Institute 
Dr. Yoan Lamarche 
5000 Belanger  
Montreal, Quebec H1T 1C8 
Phone: (514) 376-3330 
Email: yoanlamarche@gmail.com 
 
Quebec Heart and Lung Institute (University of Laval) 
Dr. Francois Dagenaise 
2725, Chemin Sainte-Foy,  
Québec (QC) G1V4G5 
Phone: (418) 656-8711 (3797) 
Email: francois.dagenais@chg.ulaval.ca 
 
Study Design: 
A five centre prospective, randomized, open, blinded endpoint (PROBE) 
controlled trial using assessor blinding and intention-to-treat analysis. 
Expected number 
of participants: 
244 individuals (122 in each arm) split up evenly between five study sites. 
Intervention: 
Patients in the Prehab group will receive, in addition to the standard of care, a 

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four to eight-week comprehensive exercise therapy and education program at a 
community-based CR facility (see details in appendix).  Patients will be asked to 
complete at least two sessions of supervised, structured exercise class plus have 
the option to attend one additional exercise class per week for a minimum of 
four weeks up to the time of their surgery, with progression to a moderate to 
high-intensity interval program based on the supervised assessment of the 
patient’s capabilities. 
Prehab participants will also attend four education sessions on topics such as risk 
factor reduction, medication use, cardiovascular physiology, smoking cessation, 
healthy eating, exercise, and stress management and promotion of self-managed 
care. 
Duration per 
participant: 
~ 4-8 weeks 
Inclusion criteria 
(all need to be 
fulfilled for 
eligibility): 
1. Patients, aged 60 years or older, undergoing elective isolated coronary 
artery bypass grafting (CABG), aortic valve repair/replacement for 
moderate aortic stenosis or severe regurgitation, mitral valve 
repair/replacement for moderate stenosis or severe regurgitation or 
combined CABG/valve procedures. 
2. Patients with Clinical Frailty Score (CFS) ≥3 (managing well) and < 7 (8 = 
very severely frail, approaching end-of-life or 9 = terminally ill) at time of 
acceptance for cardiac surgery. 
3. Patients with an estimated ≥ 4 week wait time. 
Exclusion criteria 
(any of the 
following factors 
will result in 
ineligibility): 
1. Patients who have unstable or recent unstable cardiac syndrome as 
defined by:  
 
Severe heart failure (NYHA IV) or angina (CCS class IV) symptoms.  
 
Critical left main (LM) coronary disease. Hospitalization for arrhythmias 
 
CHF or acute coronary syndrome prior to randomization.  
2. Patients who have severe left ventricular obstructive disease (defined 
by):  
 
Severe aortic or mitral stenosis (aortic or mitral valve area 
<1.0cm2 or mean gradient > 40 mmHg or > 10mmHg 
respectively) 
 
Dynamic left ventricular (LV) outflow obstruction. 
3. Patients who have demonstrated exercise induced ventricular 
arrhythmias or have experienced a recent hospitalization for 
arrhythmias; 
4. Patients who have cognitive deficits that would preclude rehabilitation; 
5. Patients who have physical limitations that would preclude 
rehabilitation; 
6. Patients who are unable to attend the Prehab program. 
Primary 
outcomes: 
Proportion of patients with hospital length of stay >7 days 
Secondary 
outcomes: 
(1) pre-operative frailty, (2) exercise capacity, (3) physical activity behavior, (4) in-
hospital outcomes, (5) 1-year clinical outcomes, (6) 1-year health-related quality 
of life, (7) cost-analysis. 
Safety: 
Safety data including new hospitalization, worsening angina or heart failure and 
arrhythmias will be captured and all adverse events will be reportable to the 

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study Data Safety Monitoring Board (DSMB). 
 
Safety Monitoring: Clinical stability during the pre-habilitation period is to be 
evaluated twice per week by the CR team using clinical questioning in 
comparison to their baseline stress test. All cases will be reviewed in conjunction 
with the attending physician. 
Statistical 
methods and 
sample size 
calculation: 
The sample size calculation was based on the primary objective – determining 
the effect of Prehab on rates of prolonged hospital length of stay > 7 days.  Our 
preliminary data, demonstrated the proportion of frail patients in the Control 
group with a hospital length of stay > 7 days to be 58.3%. For the Prehab group, 
based on improvements in functional capacity in our pilot RCT and the work by 
Arthur et al.14, we believe an absolute 20% reduction in proportion of patients 
that require prolonged hospital length of stay of greater than 7 days, is feasible. 
A sample size of 194 individuals (97 in each group) will be required for a two-
tailed test at an alpha of 0.05 and power of 80%. All patients assigned to the pilot 
Prehab group completed the intervention, however, we are mindful that we will 
be recruiting frail, elderly patients who may have a higher dropout rate. Hence, 
we are estimating a 20% dropout rate and plan to recruit 244 individuals (122 in 
each study arm) to achieve an eventual sample size of 194 after dropout. 
Time schedule: 
Planned start of study:  April 2014 
Planned end of study:  May 2017 
Planned duration:  3.5 years 
Table of Contents 
 
Study Synopsis .............................................................................................................................................. 1 
Table of Contents .......................................................................................................................................... 4 
Terms and Abbreviations .............................................................................................................................. 8 
Executive Summary ..................................................................................................................................... 10 
1 General Information ................................................................................................................................ 11 
1.1 
Title ................................................................................................................................................ 11 
1.2 
Study Management Committee .................................................................................................... 11 
1.3 
Coordinating Centre ...................................................................................................................... 11 
2 Background and Rationale for Project ..................................................................................................... 11 
2.1 Introduction ...................................................................................................................................... 11 
2.2 Exercise Rehabilitation ...................................................................................................................... 11 
2.3 Identification of Potential Opportunity ............................................................................................ 12 
2.4 The PREHAB Study – Primary Research Questions/Hypotheses ...................................................... 12 
3 Study Design ............................................................................................................................................. 12 
3.1 Methodological Approach ................................................................................................................ 12 
3.1.1 Preliminary Data Informing Study Methodology ....................................................................... 12 

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3.2 Study Design, Setting, Population ..................................................................................................... 14 
3.3 Eligibility Criteria ............................................................................................................................... 14 
3.3.1 Inclusion Criteria (all need to be fulfilled for eligibility)............................................................. 14 
3.3.2 Exclusion Criteria (any of the following factors will result in ineligibility) ................................. 14 
3.4 Operational Definitions ..................................................................................................................... 14 
3.4.1 Baseline Clinical Characteristics ................................................................................................. 14 
3.4.2 Frailty Assessments .................................................................................................................... 15 
3.4.3 In-Hospital Outcomes ................................................................................................................ 15 
3.4.5 Three-Month Clinical Outcomes and Health-Related Quality of Life (HRQoL) .......................... 15 
3.4.6 One-Year Clinical Outcomes and Health-Related Quality of Life (HRQoL) ................................ 16 
3.4.7 Physical Activity .......................................................................................................................... 16 
3.5 Study Protocol ................................................................................................................................... 17 
3.5.1 Screening implementation Plan ................................................................................................. 17 
3.5.2 Safety and Baseline Assessments .............................................................................................. 17 
3.5.3 Randomization ........................................................................................................................... 17 
3.5.4 Standard care ............................................................................................................................. 17 
3.5.5 Prehab Intervention ................................................................................................................... 18 
3.5.6 Variable Waitlist Time ................................................................................................................ 21 
3.6 Data collection .................................................................................................................................. 22 
4 Safety Monitoring .................................................................................................................................... 23 
5 Statistical Analysis Plan ............................................................................................................................ 23 
5.1 Measures/Outcomes: ....................................................................................................................... 23 
5.1.1 Primary Outcome ....................................................................................................................... 23 
5.1.2 Secondary Outcomes ................................................................................................................. 23 
5.2 Statistical/Analytical Plan .................................................................................................................. 23 
5.3 Sample Size Calculation .................................................................................................................... 24 
5.4 Cost Analysis ..................................................................................................................................... 24 
6 Data Management ................................................................................................................................... 24 
6.1 Site Monitoring ................................................................................................................................. 24 
6.2 Data Recording and Document Retention ........................................................................................ 25 
6.3 Data quality assurance ...................................................................................................................... 25 
6.4 Funding ............................................................................................................................................. 25 
7 Participating Sites ..................................................................................................................................... 25 
8 Operations Structure ............................................................................................................................... 26 
8.1 Organization Chart ............................................................................................................................ 26 

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8.2 Steering Committee .......................................................................................................................... 26 
8.3 Study management committee ........................................................................................................ 26 
8.4 Coordinating Centre .......................................................................................................................... 26 
8.5 Principal Investigator/Project Lead ................................................................................................... 26 
8.6 Regional PI’s/Site Leads .................................................................................................................... 27 
8.7 Research Coordinator ....................................................................................................................... 27 
8.7 Research Assistants ........................................................................................................................... 28 
8.8 Students ............................................................................................................................................ 28 
9 Project Timeline ....................................................................................................................................... 29 
9.1 Research Deliverables and Milestones ............................................................................................. 29 
9.2 Preliminary Project Schedule ............................................................................................................ 29 
10 Project Impact ........................................................................................................................................ 30 
10.1 Project relevance and impact ......................................................................................................... 30 
10.2 Contributions to HQP ...................................................................................................................... 31 
10.3 KT framework/platform .................................................................................................................. 31 
10.4 Project engagement ........................................................................................................................ 32 
Tables .......................................................................................................................................................... 33 
Table 1 - How the PREHAB Study fits in the Technology Evaluation Framework ................................... 33 
Table 2 - Characteristics of Included Studies In Frailty and Cardiac Surgery Systematic Review ........... 34 
Table 3 - Outcomes of Included Frailty and Cardiac Surgery Studies ..................................................... 35 
Table 5 - Intraoperative Variables ........................................................................................................... 37 
Table 8 - Comparison of operative characteristics between Standard care and Prehab groups ........... 39 
Figures ......................................................................................................................................................... 41 
Figure 1 - An example of the journey faced by a “typical” frail elderly person undergoing cardiac 
surgery .................................................................................................................................................... 41 
Figure 2 - (Panel A) Flowchart of preliminary frailty study cohort recruitment over a 12-month period 
(July 9, 2012-July 31, 2013). Overall consent rate 77% with a study completion rate of 73%................ 42 
Figure 3 - (Panel A): Total walking distance achieved by Standard care and Prehab patients during a 6-
minute walking test. Values are mean ± standard error; Standard care n= 7; Prehab n=7. a different 
from baseline (p<0.05); # different from Standard care (p<0.05). Preop= one week pre-oeratively; 
Postop= three months post-operatively. ................................................................................................. 43 
Figure 4 - Proposed PREHAB Study Process Overview – Recruitment and Study Protocol ..................... 44 
Figure 5 - A. Predicted Flow of Patients Per 14 Month Planned enrollment period.  B: Projected Study 
Timeline.  C: Timeline for Individual Objectives ...................................................................................... 45 
Appendices .................................................................................................................................................. 46 
Appendix I - Modified Fried Criteria (1-7) ............................................................................................... 46 
Appendix II - Five item Geriatric Depression Scale (5-GDS) .................................................................... 47 

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Appendix III - The Patient Health Questionnaire (PHQ-9) ...................................................................... 48 
Appendix IV – Pilot Project Manuscript ..................................................... Error! Bookmark not defined. 
References ……………………………………………………………………………………………………………………………………………56 
 
 
 

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Terms and Abbreviations 
5-GDS 
5-point geriatric depression scale.  See Appendix II - Five item Geriatric Depression Scale (5-
GDS) 
6MWT 
6 Minute Walking Test.  See 3.5.5.4.2 Exercise stress test and 6-minute walk test (6MWT). 
ACSM 
American College of Sports Medicine.  http://www.acsm.org 
ADL 
Activities of Daily Living.  From Older Americans Resources and Services Scale.  See 
http://centerforaging.duke.edu/services/141. 
ANOVA 
Analysis of Variance 
CABG 
Coronary Artery Bypass Graft 
CAM-ICU 
Confusion Assessment Method for the Intensive Care Unit.  See 
http://www.icudelirium.org/docs/CAM_ICU_training.pdf 
CCS 
Canadian Cardiovascular Society. 
CES-D Scale 
The two-item Center for Epidemiologic Studies Depression (CES-D) Scale.  See 
http://www.scireproject.com/outcome-measures-new/center-epidemiological-studies-
depression-scale-ces-d-and-ces-d-10 
CFS 
Clinical Frailty Score 
Charlson Co-
morbidity 
Index 
See http://www.ncbi.nlm.nih.gov/pubmed/3558716?dopt=Abstract 
CHF 
Congestive Heart Failure 
COPD 
Chronic Obstructive Pulmonary Disease. 
CR 
Cardiac Rehabilitation program.  See 3.5.5.3 Core Components of Cardiac Rehabilitation. 
CRF 
Case Report Form 
CVD 
Cerebrovascular Disease 
DSMB 
Data Safety Monitoring Board 
EQ-5D 
EuroQual-5D (EQ-5D).  See http://www.euroqol.org/. 
EuroSCORE II 
See http://www.euroscore.org/calc.html. 
FI 
Frailty index. 
Functional 
Co-morbidity 
Index 
See http://www.ncbi.nlm.nih.gov/pubmed/15878473. 
GXT 
Graded maximal exercise stress test.  See 3.5.5.4.2 Exercise stress test and 6-minute walk 
test (6MWT) 
HQP 
Highly Qualified Personnel 
HREB 
Human Research Ethics Board 
HRQoL 
Health Related Quality of Life 
IADL 
Instrumental Activities of Daily Living 
ICU 
Intensive Care Unit. 
iKT 
Integrated Knowledge Translation 
IQR 
Interquartile Range 
LM 
Left Main coronary artery 
LOS 
Length of Stay. 
LV 
Left Ventrical 
MACCE 
Major Adverse Cardiac and Cerebral Event 
MI 
Myocardial Infarction 
MoCA 
Montreal Cognitive Assessment.  See http://www.mocatest.org/. 
Modified  
See Appendix I - Modified Fried Criteria (1-7) 

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MVPA 
Moderate to Vigorous Physical Activity 
NYHA 
New York Heart Association.  
http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-
Heart-Failure_UCM_306328_Article.jsp 
OARS scale 
Older Americans Resources and Services Scale.  See 
http://centerforaging.duke.edu/services/141. 
PREHAB 
Title of study.  “Pre-operative Rehabilitation for reduction of Hospitalization After coronary 
Bypass and valvular surgery.” 
Prehab 
Refers to the preoperative cardiac pre-habilitation study intervention.  For complete definition 
see section 3.5.5 Prehab Intervention.   
PROBE 
Rrospective, Randomized, Open, Blinded Endpoint trial. 
PVD 
Peripheral Vascular Disease. 
RASS 
Richmond Agitation and Sedation Scale.  See http://www.icudelirium.org/docs/RASS.pdf 
RCT 
Randomized Controlled Trial 
REDCap 
See http://project-redcap.org/. 
ROC analysis 
Receiver Operating Curve analysis. 
SF-12v2 
The Short Form-12 (SF-12v2) 
SPPB 
Short Physical Performance Battery.   See 
http://www.ndorms.ox.ac.uk/prove/documents/assessors/outcomeMeasures/SPPB_Protocol.
pdf 
StandC 
Standard Care (control group) 
STS-PROMM 
See http://riskcalc.sts.org/. 
TECH VALUE 
NET 
Technology Evaluation in the Elderly Network 
TPA 
Total Physical Acitivty 
 
 

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Executive Summary 
 
Background: More than half of all cardiac surgeries in Canada are performed on patients aged 65 years 
and older. Although cardiac surgery is generally safe, there is evidence indicating that elderly patients 
who are frail prior to surgery have a longer hospital length of stay in addition to higher rates of major 
complications and mental health disorders after surgery, as compared to non-frail, elderly patients. 
Therefore, it is critically important for the health care team to identify strategies that will provide 
improved patient outcomes through appropriate, safe and effective care for frail elderly patients, and 
furthermore will engage and empower patients in ongoing self-managed care. In Canada, when a 
patient requires heart surgery, they are placed on a “waiting list”. Patients can wait for elective heart 
surgery for as long as 3-4 months. Fortunately, this waiting system is “safe” and very few patients die 
while waiting for heart surgery. However, many patients on the waiting list experience feelings of 
powerlessness and are fearful of “making things worse”, which cause them to stop being active and to 
become even more weakened prior to their operation. A solution to address this problem is to “de-frail” 
the high-risk patient to ensure that they are better prepared to survive and thrive after cardiac surgery.  
 
Objective: We anticipate that the proposed project will inform clinical practice and facilitate the 
development of a treatment that will ensure that older patients both survive and thrive after their heart 
operation. 
 
Methods: We will conduct a clinical trial where frail patients waiting for heart surgery are randomly 
chosen to either receive the current standard of care or to participate in a 4-8week exercise/education 
“Pre-habilitation” program at a community-based cardiac rehabilitation facility in one of five cities 
(Winnipeg, MB; Saint John; NB; Halifax, NS; Montreal, QC; Saint-Foy, QC). Patients who refuse to be 
randomized or are deemed “unsafe” to participate in the exercise portion of the study but still wish to 
participate will be enrolled in a follow up registry. We will also plan to work with local health authorities 
and national advocacy bodies to ensure that this program is sustainable in the real-world in the future. 
 
Significance/Impact: 
The geriatric population is one of the fastest growing demographics undergoing 
cardiac surgery in North America (1)(2). With this, the geriatric syndrome, defined as a “constellation of 
symptoms and signs [that] describe the heterogeneous response of older adults to physiological and 
metabolic challenges,”(3) has become an important consideration in patients undergoing cardiac 
surgery. To date, no high-quality study has prospectively examined the impact of preoperative cardiac 
rehabilitation in the frail-elderly undergoing cardiac surgery and represents a noticeable knowledge gap. 
The Prehab study is specifically aimed to improve the care and establish best practice in frail elderly 
patients undergoing high-risk cardiac surgery procedures through a rigorous evaluation of the utilization 
of an inter-disciplinary and multimodal patient optimization protocol. Importantly, we have also planned 
for a detailed study analysis by key stakeholders at the health region level to determine optimal 
methodologies to implement this program following the completion of this investigation. Reducing 
anxiety, improving exercise capacity, promoting a healthy lifestyle that is durable (i.e. long-lasting) and 
improving HRQoL in the elderly are the over-riding goals of this endeavour.  
 
 

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1 General Information 
1.1 Title 
The PREHAB Study - Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass 
and valvular surgery. 
1.2 Study Management Committee 
Rakesh C. Arora (project leader), Todd Duhamel (co-site lead Winnipeg), Ansar Hassan (site lead Saint 
John), Nicholas Giacomantonio (site lead Halifax), Yoan Lamarche (site lead Montreal), Navdeep Tangri, 
Thang Ngoc Nguyen, Sarvesh Logsetty, Jitender Sareen, Colleen Metge, Hilary Grocott, Jo Anne 
Sawatzky, Kenneth Rockwood, Sean Bagshaw, Jonathan Afilalo, Jean-Francois Legare.  
1.3 Coordinating Centre 
The St. Boniface Hospital/I.H. Asper Clinical Research Institute will be the coordinating centre and data 
custodians for this national study. All data management and analysis will be conducted at the St. 
Boniface Hospital. 
2 Background and Rationale for Project 
2.1 Introduction 
Growing burdens of heart disease in an aging population has resulted in cardiac surgery being 
offered to older and increasingly frail patients with multiple co-morbidities. Newer minimally invasive 
procedures are now being performed in very frail octo- and nonagenarian patients previously deemed 
inoperable. By 2031, 25% of Canadians will be older than 65 years and by extension, greater numbers of 
frail elderly will be offered cardiac surgery. As such, it has become critically important for the health care 
system to develop strategies to improve clinical outcomes and provide patient and caregiver support.  
In Canada, when a patient requires elective cardiac surgery, they are placed on a “waiting list” for as 
long as 3-4 months. While this waiting system is safe and very few patients die while waiting for heart 
surgery, we (see 3.1.1 Preliminary Data Informing Study Methodology) and others have identified that 
patients on surgical waitlists engage in very little physical activity as they wait “in fear, and feel 
powerless”. This can be problematic for the already deconditioned frail, elderly patient as at present, 
there is no formal process for engaging frail elderly patients during this wait period. 
2.2 Exercise Rehabilitation 
Cardiovascular rehabilitation has been proven to decrease morbidity and mortality in patients 
with established and unrepaired cardiac disease(4)(5)(6)(7)(8), and to be safe in patients who are 
elderly,(9)(10)(11)(12)(13) and have heart failure (7)(14)(15)(16) in both hospital and community-based 
programs. (6)(17)(18) The proposed Prehab intervention has been designed with consultation with the 4 
cardiac rehabilitation program sites involved in the project and according to the evidence-based best-
practice guidelines published by the Canadian Association of Cardiac Rehabilitation(19), the recently 
published Canadian Cardiovascular Society Quality Indicators for cardiac rehabilitation(20) and the 
ACSM guidelines for exercise prescription in patients with cardiovascular disease (see 
http://www.acsm.org/docs/current-comments/exercise-for-persons-with-cardiovascular-disease.pdf). 
(21)All patients, in both aspects of the study, are automatically referred to participate in a postoperative 
CR program, of their own accord, after their cardiac surgery as part of current standard of care. 

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2.3 Identification of Potential Opportunity 
This wait period, therefore, presents a significant opportunity to optimize preoperative risk 
factors in these vulnerable patients. The Prehab study (an interdisciplinary model of care to maximize 
the physical, nutrition, psychological reserve and cardiac risk profile of “frail” elderly patients 
undergoing cardiac surgery) will aim to “de-frail” the high-risk elderly patient so as to improve their 
post- cardiac surgical outcomes, engage patients in active health self-management and provide 
knowledge translation for the implantation of best practices for this patient population (See Figure 1, 
Table 1, Table 2, Table 3). 
2.4 The PREHAB Study – Primary Research Questions/Hypotheses 
The primary research question(s) for the Prehab study include: 
i. 
What is the effect of a preoperative cardiac pre-habilitation (“Prehab”) program on the 
proportion of patients with hospital length of stay (LOS) > 7 days.   
We hypothesize that the performance of a multifaceted, interdisciplinary cardiac “Prehab” 
program in patients awaiting an elective cardiac surgery will reduce the proportion of frail 
elderly patients requiring a postoperative hospital LOS > 7 days. 
ii. What is the effect of a preoperative cardiac pre-habilitation program in high-risk frail elderly 
patients on (1) pre-operative frailty, (2) exercise capacity, (3) self-managed physical activity 
behavior, (4) in-hospital outcomes, (5) 3-month clinical outcomes, and (6) 3 month health-
related quality of life.   
We hypothesize that the “Prehab” program for frail elderly patients awaiting an elective cardiac 
surgery will reduce frailty, improve exercise capacity, improve self-managed physical activity 
behavior, improve in-hospital outcomes, improve clinical outcomes 3 months and 1 year 
postoperatively, and improve health-related quality of life. 
3 Study Design 
3.1 Methodological Approach 
The Prehab comprehensive inter-disciplinary program is intended to intervene to decrease frailty in 
high-risk elderly patients undergoing cardiac surgery.  
Knowledge Gap – Will Prehab work in the frail, elderly? 
Cardiovascular prevention and rehabilitation is a well-established and proven standard of care to 
decrease morbidity and mortality in patients with established and unrepaired cardiac 
disease.(4)(5)(6)(7)(8) In a landmark study by Arthur et al, 249 low-risk patients awaiting elective CABG 
were randomized either to an eight-week preoperative cardiac pre-habilitation (Prehab) program or to 
the usual care.(22) Prehab patients completed 2 exercise sessions per week and attended education 
classes on risk factor modification. These patients experienced shorter intensive care unit (ICU) and 
hospital lengths of stay (LOS) post-operatively and an improved quality of life compared to the controls, 
which persisted for 6 months following surgery. However, while this seminal study demonstrated the 
potential benefits of a “Prehab” program, this study was performed in younger, lower-risk patients and 
therefore did not address the needs of the frail, elderly patients currently being referred for cardiac 
surgery. 
3.1.1 Preliminary Data Informing Study Methodology 
The following two groundwork investigations have informed the safety and efficacy of the 
Prehab intervention and the design of the proposed phase II, randomized trial – the Prehab Study. We 
believe that the Prehab intervention will be able to “de-frail” high-risk elderly patients preoperatively 

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and will lead to sustainable motivational changes to engage in long-term healthy living following their 
cardiac procedure. The implications are that this will be ultimately transferable to percutaneous cardiac 
intervention and other non-cardiac surgery procedures in the frail elderly.  
3.1.1.1 Frailty in the Cardiac Surgery Population at St. Boniface Hospital 
We undertook a systematic review of frailty in the elderly undergoing cardiac surgery (see Table 
2 & Table 3).(23)(24)(25)(26)(27)(28)(29)(30)(31) This review demonstrated an association with 
increased frailty and a major negative outcomes ranging from increased institutional care to major 
adverse cardiac and cerebral event (MACCE) and increased in-hospital and long-term mortality after 
cardiac surgery. However, the lack of a standardized and comprehensive definition of frailty in these 
studies prevents clarity in understanding the interaction of frailty in the elderly and cardiac surgery. We 
subsequently completed a prospective examination of frailty in 133 consecutively consenting elderly 
cardiac surgery patients with high-levels of co-morbid disease (See Table 4, Table 5, Table 6 and Figure 2). 
Two definitions of frailty were used (see Appendix I): (1) Modified Fried criteria: (32)(33)(34) a patient 
was deemed “frail” if they met ≥3 of the following 7 criteria: slowness (5m gait speed)(35), weakness 
(handgrip strength measurement)(36) and questionnaires assessing self-reported weight loss, 
exhaustion (the two-item Center for Epidemiologic Studies Depression (CES-D Scale), depression (the 5-
point geriatric depression scale (5-GDS)(37)(38)), low physical activity (the Paffenbarger Physical Activity 
Index(39)(40)(41)(42)), and cognitive impairment (the Montreal Cognitive Assessment 
(MoCA)(43)(44)(45)). (2) Short Physical Performance Battery (SPPB): a patient was deemed “frail” if 
his/her composite score was ≤9 based on 5m gait speed, balance tests, and the repeated chair stand test 
(each scored from 0 to 4)(46). Using the modified Fried or the SPPB criteria, 72 (54.1%) or 69 (51.9%) 
(respectively), patients studied were deemed frail (See Table 3). Frail patients were older, more 
commonly female, had higher EuroSCORE II values (a cardiac surgery specific mortality risk prediction 
score) and lower self-health ratings. Diabetes, cerebrovascular disease (CVD), chronic obstructive 
pulmonary disease (COPD), arthritis, anemia, peripheral vascular disease (PVD), and lower serum 
albumin were also significantly associated with being frail. Notably, frailty correlated with clinically 
important measures of increased hospital LOS: total adjusted hospital LOS (median 6 days (IQR: 5 – 9) in 
non-frail vs. 8 days (IQR 6 – 12) in “frail” patients, p<0.001) and a greater proportion of patients in 
hospital > 7 days (37.7% in non-frail vs. 58.3% in frail patients, p < 0.02; See Table 4 & Table 5). This longer 
hospital stay amongst frail patients has implications for increased healthcare costs and we have 
observed an association between new and persistent mood disorders and reduced engagement in 
postoperative physical activity with a hospital LOS > 7 days after cardiac surgery. 
3.1.1.2  A Pilot RCT of a Pre-habilitation program 
We have completed a pilot, randomized control trial (manuscript proof in appendix), to demonstrate the 
safety and feasibility of a Prehab program for elective coronary artery bypass graft (CABG) patients. The 
primary outcome was walking distance based on a 6-minute walk test (6MWT). Secondary outcomes 
included 5m gait speed (23) and cardiac rehabilitation (CR) attendance Postop.  
Improving Patient Outcomes 
Fourteen patients (StandC, n=7; Prehab, n=7) completed the study (77% and 88% completion rate, 
respectively). None of the Prehab patients developed cardiac symptoms during study participation. 
Walking distance and gait speed remained unchanged in the Standard care group. Conversely, patients 
in the Prehab group increased their walking distance by +132 and +145 meters and gait speed improved 
in all seven Prehab group participants by 27% and 33% at Pre-op and Post-op, respectively (p<0.05). 
Engaging and Empowering Patients: 

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A notable finding of our pilot study was the sustainability of patient self-management, as supported by a 
higher post-operative cardiac rehabilitation (CR) enrollment amongst Prehab (100%) than StandC (43%) 
participants. 
3.2 Study Design, Setting, Population 
Prehab will be a five centre prospective, randomized, open, blinded endpoint (PROBE) (47) 
controlled trial using assessor blinding and intention-to-treat analysis. The study will be conducted at 
four academic, tertiary care hospitals (St. Boniface Hospital, Winnipeg, MB,  Queen Elizabeth II Health 
Sciences Centre, Halifax, NS, Montreal Heart Institute, Montreal, QC, Quebec heart and lung institute, 
Saint-Foy, QC) and one non-academic hospital (Saint John Regional Health Centre, Saint John, NB) that 
perform cardiac surgery. These sites were chosen based on similar patient populations and surgical 
waitlist times (48)(49). Additionally, each of these sites are partnered with one or more community-
based cardiac rehabilitation (CR) centres, which are certified medical fitness facilities dedicated to 
improving the health of the community through health promotion, disease prevention and rehabilitation 
services. These facilities offer expert guidance from certified professionals, innovative health 
enhancement programs, and provide integrated medical, rehabilitative and fitness services. 
3.3 Eligibility Criteria 
3.3.1 Inclusion Criteria (all need to be fulfilled for eligibility) 
1) Patients, aged 60 years or older, undergoing elective isolated coronary artery bypass grafting (CABG), 
aortic valve repair/replacement for moderate aortic stenosis or severe regurgitation, mitral valve 
repair/replacement for moderate stenosis or severe regurgitation or combined CABG/valve procedures. 
2) Patients with Clinical Frailty Score (CFS) ≥3 (managing well) and < 7 (8 = very severely frail, 
approaching end-of-life or 9 = terminally ill) at time of acceptance for cardiac surgery. 
3) Patients with an estimated ≥ 4 week wait time. 
3.3.2 Exclusion Criteria (any of the following factors will result in ineligibility) 
1) Patients who have unstable or recent unstable cardiac syndrome as defined by: 
a. Severe heart failure (NYHA IV) or angina (CCS class IV) symptoms. 
b. Critical left main (LM) coronary disease. 
c. Hospitalization for arrhythmias, CHF or acute coronary syndrome prior to randomization. 
2) Patients who have severe left ventricular obstructive disease as defined by: 
a. Severe aortic or mitral stenosis (aortic or mitral valve area <1.0cm2 or mean gradient > 40 mmHg 
or > 10mmHg respectively) 
b. Dynamic left ventricular (LV) outflow obstruction. 
3) Patients who have demonstrated exercise induced ventricular arrhythmias or have experienced a 
recent hospitalization for arrhythmias. 
4) Patients who have cognitive deficits that would preclude rehabilitation. 
5) Patients who have physical limitations that would preclude rehabilitation. (Unless they have agreed to 
participate in the follow-up registry) 
6) Patients who are unable to attend the Prehab program. (Unless they have agreed to participate in the 
follow-up)  
3.4 Operational Definitions 
3.4.1 Baseline Clinical Characteristics 
Preoperative patient demographics, cardiac risk profile, procedure data, surgical risk scores 
(EuroSCORE II and STS-PROMM(50)(51)(52)), medical history and medication profile, cardiac risk factors 

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and cardiac illness severity are routinely collected for all patients in the pre-existing site surgical 
databases which will be utilized for this study.  Each site will also collect co-variates of co-morbidities 
(Charlson Co-morbidity Index, Functional Co-morbidity Index (53), OARS scale for activities of daily living 
(ADL) and instrumented activities of daily living (IADL)(54) as well as postoperative complications and 
postoperative hospital LOS. In order to avoid issues caused by delayed hospital discharge due to non-
medical reasons, patients will be evaluated daily for “readiness for discharge” using a standardized set 
of criteria. Cognitive function will be measured using the Montreal Cognitive Assessment (MoCA) 
(43)(44)(45). 
3.4.2 Frailty Assessments 
Our strategy for rapid screening of frailty in a large volume of clinic patients will be to use the 9-
point Clinical Frailty Scale (CFS) (56)(See Figure 4 and appendix). The CFS is the simplest tool to implement 
at multiple centres, has a high inter-observer reliability and shows good performance (by ROC analysis) 
for risk of death or institutionalization. Due to the need to screen a large number of individuals (785 
patients; Figure 5) the use of the Modified  and SPPB are less practical to implement as routine practice in 
the outpatient clinic sites. Therefore our approach is to use a CFS score of ≥ 3 as the initial indication of 
frailty (57) . This approach will allows us to estimate degrees of frailty in a large volume of patients in a 
rapid, cost-effective and highly feasible manner. All enrolled patients will be further assessed using the 
modified Fried criteria(33)(32)(34), and a reduction of frailty will be defined as a binary value (i.e. 
frail/non-frail) using these criteria(33)(32)(34).                                                                                                                                      
The SPPB criteria will be used as a third measure.(46) As a fourth measure, our data collection 
protocol will also enable a Frailty Index (FI) calculation.(29)(56)(58)(30) The inclusion of the more 
definitive frailty evaluations are intended to gain more information about the different domains of 
frailty in the elderly to further improve the clinical frailty assessments that will be used in the future. 
To ensure reliability of this approach, we have compared the three measures of frailty (CFS, Modified  
and SPPB) on 169 elective cardiac surgery patients at the St. Boniface Hospital. The spearman 
correlation was ~0.65 for all three comparisons and the Cohen’s Kappa, which is a concordance measure 
between the different frailty definitions is ~0.50. These values indicate a moderately strong link 
between all three measures; however it is possible that they capture somewhat different domains of 
frailty.  
3.4.3 In-Hospital Outcomes 
Postoperative ICU and hospital LOS, 30-day mortality, major adverse events (death, MI, stroke 
or renal failure requiring dialysis) will be collected using existing site surgical databases. Post-operative 
CR enrollment will be assessed using administrative data from the participating CR centers.  
In our preliminary analysis, we have identified a strong association between frailty and the occurrence 
of delirium (Table 5). The participating Cardiac ICUs currently perform an agitation and delirium 
assessment once every 8 hours as standard practice. Delirium assessment will be performed in the ICU 
using the Richmond Agitation-Sedation Scale (RASS)(59) and the Confusion Assessment Method for the 
Intensive Care Unit (CAM-ICU). (60)(61)(62). As part of standard of care a blood sample will be collected 
upon placement of the arterial line in the operating room to ascertain the patient’s sodium, potassium, 
glucose, white blood cell count, hematocrit, creatinine and albumin and this data will also be 
collected.(49)(65) 
3.4.5 Three-Month Clinical Outcomes and Health-Related Quality of Life (HRQoL) 
The EuroQual-5D (EQ-5D)(66) will be administered preoperatively and at  12 weeks (time of 
routine surgical follow-up). The EQ-5D is a validated measures of HRQoL and was selected due to its 
simplicity and proven clinical relevance. (67)(68)(69) 

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3.4.6 One-Year Clinical Outcomes and Health-Related Quality of Life (HRQoL) 
The EuroQual-5D (EQ-5D) will be administered preoperatively and at 1 year following surgery. 
The EQ-5D is a validated measures of HRQoL and was selected due to its simplicity and proven clinical 
relevance. 
3.4.7 Physical Activity 
We will assess exercise capacity using a 6-minute walking test (6MWT). The 6MWT is a practical 
and simple test that has is a negative correlation between total distance walked and length of hospital 
stay (r= -0.62) (70) and is suitable for use amongst patients with moderate-severe heart and lung 
disease. (71)Physical activity behavior will be measured using multi-directional accelerometers over a 
seven-day period, based on the methods described by Colley et al. (72) We have previously used these 
approaches to assess physical fitness and activity amongst cardiac patients. 
3.4.8 Patient Interview Questionnaires/Instruments – The Interview Package 
 
The following questionnaires will be completed at baseline, preoperatively, 3-months following 
surgery and one year following surgery for both arms of the study.  The questionnaires will be 
administered using the REDCap software with the participant completing the survey on a computer. 
1. Seattle Angina Questionnaire (SAQ) 
2. Kansas City Cardiomyopathy Questionnaire (KCCQ) 
3. Montreal Cognitive Assessment Form (MoCA) 
4. 5-Item Geriatric Depression Scale (GDS-5) 
5. Generalized Anxiety Disorder 7 Item Scale (GAD-7) 
6. OARS Scale for Activities of Daily Living (ADL)/Instrumental Activities of Daily Living (IADL) 
7. EuroQol 5-Dimension 5-Level (EQ-5D5L) 
8. EuroQol Visual Analog Scale (EQ-VAS) 
9. Paffenbarger Physical Activity Scale 
10. Nutrition/Exhaustion Questionnaire 
11. Self-efficacy for Exercise Questionnaire 
12. Baseline Demographics (only done once at baseline) 
 
Patients who prefer to enrol in the registry will not complete any preoperative questionnaires. They 
will be contacted over the telephone at 3-months and one year following surgery and complete the 
following questionnaires: 
1. Demographic information  
2. Generalized Anxiety Disorder 7 Item Scale (GAD-7) 
3. Geriatric Depression Scale (GDS) 
4. OARS Scale for Activities of Daily Living (ADL)/Instrumental Activities of Daily Living (IADL) 
3.4.9 Data Collection Instruments – The Data Collection Package 
The following variables will be collected for participants in both arms of the trial, as well as the 
registry.  This information will be obtained from existing electronic databases as well as hospital 
charts. 
1. Patient Demographics/Hospital Length of Stay 
2. Preoperative Cardiac Information 
3. Preoperative Comorbidities 
4. Lab Results (pre and post-op) 
5. Echocardiogram Information 
6. Angiogram Information 
7. Procedure Information 

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8. Medications (pre and post-op) 
9. Post-Operative Delirium 
10. Post-Operative Complications 
11. 30 Day Readmission 
12. 12 Month Readmission 
3.5 Study Protocol 
3.5.1 Screening implementation Plan 
Following training, clinicians will complete a CFS score for every new cardiac surgery consult at 
each of the participating sites. Patients with a CFS ≥ 3 will be eligible for enrolment and notification will 
be sent to the site coordinator. Patients who are eligible for the study (CFS ≥ 3) will either be consented 
in person or via telephone consent process. Patients with a CFS ≥ 3 that either refuse to be randomized 
or are deemed “unsafe” will be given the opportunity to enroll in a follow up registry. 
3.5.2 Safety and Baseline Assessments 
A medical director, at each site, will oversee all cases and ensure patient eligibility and safety for 
program initiation and throughout program attendance for the study duration. All eligible and 
consented patients will be evaluated at baseline to ensure angina stability. Exercise prescription will be 
determined utilizing the standard practice of the Karvonen Equation adjusted according to pre-program 
exercise stress test. (21)Patients will also undergo a standard 6MWT (73)(74)(75)(76)(77)(78) and will 
repeat the 6MWT at the preoperative time point in both the control and Prehab groups to determine 
impact of the intervention. The 6MWT was chosen because it requires minimal infrastructure and 
personnel to complete and has been demonstrated to be a valid prognostic tool for patient outcomes 
and is comparable to an exercise-stress test. (73)(75)(76)(77)This approach enables us to avoid potential 
scheduling issues that occur if a patient’s surgical date is moved up.  
Patients who are deemed appropriate for enrolment into study will be randomized, following 
the completion of the baseline data collection, to one of two trial arms – control (standard of care 
(StandC) or treatment (Prehab). Baseline risk factor evaluation, anthropometrics, clinical markers, 
patient questionnaires (including frailty scores, cognitive assessment, and quality of life data) and 
physical activity data measured using accelerometers will be collected for all patients and repeated pre-
operatively and at three-month follow up. Safety data including new hospitalization, worsening angina 
or heart failure and arrhythmias will be captured and all adverse events will be reportable to the study 
Data Safety Monitoring Board (DSMB). All patients in both groups will be referred to postoperative CR 
programming, as per local practice. 
3.5.3 Randomization 
Trial Randomization using REDCap: The Randomization Module within REDCap allows 
researchers to randomly assign participants to specific groups. Dr. Logsetty has experience and will be 
responsible for study randomization. Assessors of pre- and post-operative data will be blinded to 
treatment group allocation.(47) 
3.5.4 Standard care 
Patients in the StandC group will receive care as is currently delivered to patients awaiting 
cardiac surgery at each site. At present, patients are advised to rest and participate in very light intensity 
physical activity while awaiting surgery. At 1-2 weeks prior to their scheduled surgical date, the patient 
attends a single three hour cardiac pre-assessment with a nurse practitioner and cardiac 
anesthesiologist. In addition, a cardiac nurse counsels each patient on healthy behaviors (e.g. smoking 
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3.5.5 Prehab Intervention 
Patients in the Prehab group will receive, in addition to the above standard of care, an eight-
week comprehensive exercise therapy and education program at a community-based CR facility. This 
program will target both the physical and psycho-social-cognitive aspects of cardiac disease and frailty. 
In brief, participants will be required to complete an intake health status assessment by the CR team 
including a physiotherapist, cardiovascular nurse, and dietitian and complete a symptom-limited graded 
exercise stress test according to the American College of Sports Medicine Guidelines for Exercise Testing 
and Prescription 7th Edition.(79) Patients will be asked to complete at least two sessions of supervised, 
structured exercise class plus have the option to attend one additional exercise class per week for eight-
weeks, with progression to a moderate to high-intensity interval program based on the supervised 
assessment of the patient’s capabilities. This has been shown to be safe and effective in unrepaired 
heart failure and elderly patients.(7)(8)(9)(14)(16)(80)(81)  Prehab participants will also attend four 
education sessions on topics such as risk factor reduction, medication use, cardiovascular physiology, 
smoking cessation, healthy eating, exercise, and stress management and promotion of self-managed 
care.(82)(83)(84) Principles of shared decision-making will be utilized with the Prehab intervention, 
where training for providers and patients involved in the intervention will have shared control of 
treatment decisions.(82)(83)(84) 
Participants in the intervention group will receive a baseline health assessment at their local 
cardiac rehabilitation facility. This assessment will include the facility’s standard health and fitness 
assessment: health screening, blood pressure, lung function, lab work, and body composition. This 
assessment will provide the basis for an individualized exercise prescription, to include an 8 week, 
individualized, symptom limited, exercise program.  
Briefly, patients will be required to attend a minimum of 2 structured exercise sessions per 
week. The program will last a total of 8 weeks, or until the patient undergoes their cardiac procedure 
(minimum of 4 weeks for data collection purposes).  Patients will be encouraged to walk daily in addition 
to attending the scheduled exercise sessions. Exercise will be prescribed according to standardized 
procedures at the medical fitness facility for their cardiac rehabilitation program. Briefly, participants 
will complete a warm-up/stretching session of approximately 15 minutes at the beginning of each 
session. Aerobic exercise will be prescribed at 40-60% of heart rate reserve (Karvonen Formula) based 
on baseline exercise stress test data. Aerobic exercise will last approximately 10-30 minutes depending 
on individual tolerance and level of conditioning. Aerobic prescription will progress to high intensity 
exercise in the context of symptom-limited, interval training up to 85% of maximal aerobic capacity 
based upon recommendations by the cardiologist. Individual interest will determine the modality of 
exercise chosen. Options will include walking, cycling, stretching and resistance training with body 
weight or resistance bands following clearance by a cardiologist. Intensity will be progressed based on 
close communication between healthcare providers and participants. Sessions will be concluded with a 
10-minute cool down period.  
In addition to the exercise program, patients will be required to participate in 4 educational 
sessions tailored to self-management for cardiac rehabilitation. Examples of educational sessions 
offered by professional staff at the medical fitness facility include:   
 
Exercise and Action Planning (Kinesiologist) 
Risk Factor Modification (Nurse/Physiotherapist) 
Cardiac Electrical System (Nurse/Physiotherapist) 
Cardiac Circulation (Nurse/Physiotherapist) 
Cardiac Muscle Function (Nurse/Physiotherapist) 
Resistance Training (Kinesiologist) 
Body-Mind Connection (Social Worker) 

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Heart Healthy Eating (Dietician) 
Looking Forward; transitions, barriers, self-management (Kinesiologist) 
Diabetes Education (Dietician) 
Emotional Impact of Heart Disease (Social Worker) 
Label Reading (Dietician) 
Preventing Relapse (Social Work) 
Stress Busters (Psychologist) 
Tracking Food Choices (Dietician) 
Smoking Cessation (Social Worker) 
Relaxation Techniques (Psychologist) 
 
Participants in the intervention group will be asked to keep a log of their attendance at both the 
exercise and educational session. Additionally, an exercise log completed by individual patients will track 
the mode of exercise completed in addition to monitoring compliance with the intervention. 
 
3.5.5.1 Patient orientation  
All patients enrolled in the PREHAB CR intervention program (PREHAB patients) will meet with a 
nurse or fitness professional delivers this session or fitness professional, who gives patients a tour of the 
CR centre facility, outlines the programs offered, describes who the CR staff are and their roles, and 
explains the overall goal of cardiac rehabilitation. Patients are also given the opportunity to ask 
questions regarding the CR program. 
3.5.5.2 Program delivery 
The PREHAB CR program will be delivered by a multi-disciplinary group consisting of physicians, 
nurses, fitness professionals, physiotherapists, dieticians, and psychologists. This approach allows the CR 
team to share knowledge, skills, and patient care responsibilities. A medical advisor, at each site, is 
responsible for the safety of enrolled PREHAB patients. Additionally to support patient safety, an 
emergency plan is in place with appropriate equipment (e.g. Defibrillator, nitroglycerine) and medical 
staff is available during patient care hours. 
3.5.5.3 Core Components of Cardiac Rehabilitation 
The PREHAB CR program adheres to the core components of CR outlined by the Canadian 
Association for Cardiac Rehabilitation Guidelines (85). These core components include: systematic 
patient referral processes, patient assessments, health behavior interventions and risk factor 
modification, exercise training, leisure time activities, outcomes assessment programs, continuous 
quality improvement programs, and continuous professional development programs.  
3.5.5.4 Patient assessment 
All patients complete a series of assessments that are kept in a client case file. All patient health 
information collected and will be is kept in a secure room and a lockable filing cabinet. Patient health 
information is used to assist the CR health care team to optimize patient treatment during the CR 
program.  
3.5.5.4.1 Risk factor assessment 
Patients who are enrolled in PREHAB will complete a one hour patient assessment from nurse or fitness 
professional. This assessment includes a medical history and physical examination to collect information 
on cardiac risk factors or other underlying conditions that could affect their treatment. Furthermore, 
each center collects blood samples for information on patient cholesterol, fasting blood glucose, and 
hemoglobin. In most cases, patients have received screening and diagnostic procedures from the 

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hospital in which their cardiac event was acutely managed. This information serves as a decision-making 
tool for CR staff to make informed decisions on patient treatment during CR. The information collected 
from this patient assessment is used to stratify a patient’s risk for experiencing a future cardiac event. 
3.5.5.4.2 Exercise stress test and 6-minute walk test (6MWT) 
All PREHAB patients complete a graded maximal exercise stress test (GXT), which is supervised by an 
MD, exercise specialist, nurse, and electrocardiogram technician. Patients complete the Modified Bruce 
treadmill protocol. This protocol was designed specifically for testing patient cardiac function during 
exercise. Briefly, each stage of the test lasts three minutes, where speed and grade is increased at each 
stage. The first stage starts at 1.7 miles per hour and a 10% grade for the first three minutes and is 
progressively increased thereafter by increasing both speed and grade. There are a total of seven stages. 
The test is terminated if the patient voluntarily withdraws, or if the CR staff notices any cardiac 
abnormalities during the test (e.g., ST-abnormalities, no increase in heart rate with an increase in 
workload). Information collected from the stress test is then used to assist CR staff to prescribe exercise 
for the patient. A 6MWT will performed in all patients along with the GXT as described in the 
methodology. 
3.5.5.4.3 Psychosocial assessment 
The research literature supports the contention that depression and anxiety negatively affect the 
cardiovascular health status of patients. Therefore, patients are encouraged, particularly if they had a 
previous psychosocial disorder, to see a clinical psychologist for an initial assessment. This assessment is 
used to counsel the patient on ways in which they can appropriately manage their cardiac disease in 
combination with their psychosocial disorder. Patients also complete the 5 item Geriatric Depression 
Scale (GDS-5). 
3.5.5.4.4 Nutritional assessment 
PREHAB patients will see the Registered Dietician at the CR Centre to optimize their diet to help manage 
their disease. Prior to the assessment, patients complete a 3-day food recall to help the Dietician in 
developing a personalized message and treatment strategy. Furthermore, this assessment assists 
patients in gaining a better understanding of the ways in which different types of fats, salt intake, as well 
as other components of the diet affect cardiovascular health. Patients also have the option to receive a 
follow-up visit to receive further counseling.  
3.5.5.5 Health behavior interventions and risk factor modification 
PREHAB patients all receive a comprehensive, multi-faceted health behavior intervention with 
the goal of positively modifying their risk factor profile. This includes nutritional counseling, lipid 
management, hypertension management, smoking cessation, weight management, diabetes 
management, adherence to prescribed pharmacotherapy, psychosocial management, and physical 
activity counseling. 
3.5.5.6 Exercise training and leisure time activities 
After the baseline assessments described above are completed, the PREHAB patient will engage 
in the 8-week PREHAB CR exercise therapy program. The first four weeks of the program constitutes a 
more structured program, the CR Centre staff closely monitor the patient during their exercise program 
and follows their progress. The patient attends the CR Centre for two 1 hour sessions of exercise training 
for the first four weeks. Exercise intensity is typically prescribed at 85% of their maximum heart rate-
reserve, unless advised otherwise by the Internist. The remaining 4 weeks is less-structured and the 
patient is given more autonomy on the manner in which they complete their exercise therapy program. 
The patient engages in an individually prescribed exercise program consisting of aerobic, strength, and 
flexibility training. Frequency, time, and type of exercise varies depending on what the patient chooses. 
The majority of aerobic exercises consist of walking, cycling, rowing, and many machine-based aerobic 

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exercises. A Strength and Stretch class is also offered to increase muscle strength and endurance, and 
flexibility.  
In addition to participating in physical activity at the CR Centre, patients are encouraged to 
participate in physical activities during their leisure time. This includes, but is not limited to, walking 
outdoors, gardening, household chores, grocery shopping, and cycling. This component of the CR 
program is designed to help patients manage their cardiac disease after they complete CR. Patients will 
be assigned an accelerometer to wear to be able to compare self-assessed exercise reporting with 
objective measurements. 
3.5.5.7 Outcomes assessment 
Patients are evaluated after they complete the CR program based on their outcomes. Patients 
are assessed based on several different outcomes, including clinical, health, educational, and behavioral 
outcomes. To assess these outcomes, patients complete the baseline assessments (described under the 
Patient assessment section) after they complete the 8-week PREHAB CR program. A key evaluation will 
be the 6MWT to assess exercise capacity pre and post-program. 
3.5.5.8 Continuous quality improvement programs 
Each CR program will engage in continuous evaluation of their program to provide high quality care 
for their patients.  The key components of this evaluation include: 
 
Eliminating defects in the CR delivery process and adding features to better meet the needs of 
the patient needs and preferences. 
 
Focusing on the core processes to improve the CR program. This includes statistical methods 
and tools to identify desired performance levels, measurement of current performance, and to 
interpret and take action as necessary. 
 
Involvement of all CR staff in quality improvement. Utilization of structured teams and councils 
to advise and plan quality improvement strategies are utilized. 
 
Setting high standards for performance. 
3.5.5.9 Continuous professional development programs 
This process involves keeping up to date with the most relevant knowledge on delivering the 
appropriate care to patients. Continuous professional development includes: 
 
Continuous learning processes that update relevant knowledge, skills, and attitudes. 
 
Maintenance of professional continuing education credits. 
 
Keeping up to date on the appropriate certifications (e.g., CPR training) 
 
Staff engagement in employee mentorship of students and other professionals, professional 
certification programs, and attendance in annual meetings relevant to CR. 
3.5.6 Variable Waitlist Time 
We acknowledge that the time on the waiting list may be variable. For example, in Manitoba the 
median waitlist time is 12 weeks (range: 3-31 weeks). The median waitlist time for our preliminary study 
was 62 days and such we believe that enrolled patients will not be subjected to any undue harm. The 
recommended standard wait for elective cardiovascular surgery should not exceed six weeks,(86) 
however the best physiological outcomes for patients attending cardiac rehabilitation is at least eight 
weeks(21)(19)(20)(79), or occur by participants who attend more than 25 sessions of CR.(11) After 
consulting with the associated CR program sites and our expert co-investigators, it was determined that 
the preferred Prehab intervention would be 8 weeks because it was deemed that clinically stable, frail, 
elderly patients could feasibly achieve measurable health benefits and risk factor modification over this 

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time frame.(87) However due to the variability in the waitlist times participants would still be eligible 
with a waitlist time of 4 weeks minimum. 
 
What if patients are unable to complete the Prehab program due to a change in surgical date?  
It is possible that a patient may not complete the full 8 week program due to scheduling changes for 
their procedure. We and others (78)(11)have seen functional and health behavior improvements in as 
little as 2-4 weeks. Notably, 2 patients in our pilot Prehab project participated in the program for only 
3.5 weeks but still improved their total distance walked by an average of 174 meters (43% 
improvement). Our data is supported by Fiorina and associates and indicates that as few as 15 days of 
CR can improve total distance walked by as much as 40%. With this in mind, the Prehab program has 
been structured to provide the more intensive nutritional counselling, educational, psychosocial and 
exercise therapy during the first four weeks of the program and engage Prehab participants to take 
control of their self-managed care for the remaining program. This will enable participants to gain 
meaningful benefits in the event scheduling changes prevent the completion of the 8 week program. 
 
3.5.6 Qualitative review of PREHAB Study 
We engaged patients prior to conducting the PREHAB study to uncover whether patients would 
participate in a prehabilitation intervention. After study completion we want to continue the 
conversation with all patients both in the intervention arm, standard care arm as well as registry 
participants. 
 
During the post study intervention we will conduct a series of individual interviews and survey 
components to enlist patient-centered response and opinion to the study intervention. We wish to 
know if there were barriers for participation, any factors that reduced adherence to the study as well as 
an overall satisfaction with the intervention. We also would like to discuss how improvements can be 
made after a participant has finished the intervention part of the study. For non-intervention patients 
we want to see if they went to cardiac rehab post-surgery and what its impact was on their recovery.  
 
Additionally, A small group of participants and their caregivers from the primary site will be contacted 
and asked to participate in a more extensive patient panel session to better understand the patient 
valued experience of the intervention that was provided to participants and ways to improve delivery 
and adherence. We will conduct 3 group sessions of patients and their caregivers lasting approximately 
2-3 hours. We will be following a general format with topic questions; however, we expect a very open 
conversation. All information will be transcribed and stored. Information identified within these sessions 
may be used to develop tool to be used to improve communication and adherence to care based 
interventions during the perioperative process.  (See PREHAB Patient panel protocol)  
 
We will conduct interviews with patients based on availability. As we are a multi-site intervention we 
will interview patients from the study who are not local to the primary site. We will contact current 
participants and enroll patients who are interested in the study. We will also identify patient perspective 
with cardiac rehabilitation post-surgery .  
 
3.6 Data collection  
All participants will meet with the research staff at nine time points: 1) twice at time of 
enrolment after their acceptance for a surgical procedure (i.e. baseline pre-intervention); 2) 4 weeks 
following randomization into either standard care or intervention group; 3) twice, 1-week 

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preoperatively (i.e. Pre-op); 4) twice, 3 months postoperatively; and, 5) twice, 1 year postoperatively 
(Figs. 4 and 5). Data collection will occur from both written and electronic medical records sources (i.e. 
patient information systems, where applicable). Existing perioperative surgical, ICU and hospital data 
will be used to capture patient demographics, procedure urgency, intraoperative procedure and 
anesthetic variables, cardiopulmonary bypass information, blood product utilization, mechanical 
ventilation, delirium/coma, ICU and hospital LOS, major adverse events, infection and ICU and hospital 
recidivism are collected in institutional databases. 
Patients deemed “unsafe” to be enrolled in the exercise portion of the study or that have 
refused to be randomized but have consented to participate in the follow up registry will be contacted 
via telephone by research staff after their surgeries at two time points: 1) 3-months after surgery; and, 
2) 12-months after surgery.  A data sharing agreement, in compliance with provincial patient 
confidentiality legislation will be created to permit planned analysis. We have previously utilized these 
data collection methods.(49)(65)(88)(89)(90) 
4 Safety Monitoring 
Safety data including new hospitalization, worsening angina or heart failure and arrhythmias will be 
captured and all adverse events will be reportable to the study Data Safety Monitoring Board (DSMB). 
The DSMB is an independent group of experts that advises study investigators. They are responsible to 
periodically evaluate the study data for participant safety and study conduct, in addition to making 
recommendations concerning the modification and/or termination of the trial.  
 
Safety Monitoring: Clinical stability during the pre-habilitation period is to be evaluated twice per week 
by the CR team using clinical questioning in comparison to their baseline stress test. All cases will be 
reviewed in conjunction with the attending physician. 
5 Statistical Analysis Plan 
5.1 Measures/Outcomes: 
 
For the PREHAB study, we propose to capture data to enable evaluation of effect of a preoperative 
cardiac pre-habilitation program on: 
5.1.1 Primary Outcome 
Proportion of patients with hospital length of stay >7 days. 
5.1.2 Secondary Outcomes 
(1) pre-operative frailty, (2) exercise capacity, (3) physical activity behavior, (4) in-hospital outcomes, (5) 
1-year clinical outcomes, (6) 1-year health-related quality of life, (7) cost-analysis. 
5.2 Statistical/Analytical Plan 
Objective 1: To determine if Prehab reduces the proportion of frail elderly patients requiring a prolonged 
hospital length of stay of >7 days. A univariable analysis will be undertaken to determine if hospital LOS 
> 7 days is associated with frailty and other patient-level factors. A stepwise multivariable logistic 
regression model will then be developed to determine if Prehab attendance is independently associated 
with a decreased risk of prolonged hospital length of stay > 7 days. As a secondary analysis, hospital LOS 
will also be compared as a continuous variable between the Prehab and standard care groups using a 
Mann-Whitney test. 

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Objective 2: Does attending Prehab influence frailty, exercise capacity, physical activity behavior, in-
hospital complications, and HRQoL? Although we will employ four different measures of frailty, based 
on our preliminary data and based on a Task Force’s position statement(90), the Modified Fried Criteria 
will be the primary frailty outcome over time from baseline to the end of Prehab program (pre-
operatively), or from baseline to the 3-month post-operative follow-up. The primary measure of exercise 
capacity will be the 6MWT and will be analysed with univariable linear regression models to evaluate 
the association between the 6MWT and Prehab attendance. Accelerometers will be used to objectively 
measure the number of minutes spent performing moderate to vigorous physical activity (MVPA) and 
total physical activity (TPA) per day for a period of 7 days and compared between groups. A composite 
outcome for a major adverse cardiac event (i.e. MACCE = in-hospital stroke, myocardial infarction, renal 
failure requiring dialysis and death) and delirium will be compared between groups using a Chi-Square 
or Fisher’s Exact test. A multivariable logistic regression will be used to identify if Prehab  is 
independently associated with in-hospital delirium. The SF-12v2 and EQ-5D scores, after normative 
standardization, will be analyzed through use of a repeated ANOVA to allow for a standardized group 
and group/time interaction effect estimation. 
5.3 Sample Size Calculation 
The sample size calculation was based on the primary objective – determining the effect of Prehab on 
rates of prolonged hospital length of stay > 7 days.  Our preliminary data, demonstrated the proportion 
of frail patients in the Control group with a hospital length of stay > 7 days to be 58.3%. For the Prehab 
group, based on improvements in functional capacity in our pilot RCT and the work by Arthur et al14,  
we believe an absolute 20% reduction in proportion of patients that require prolonged hospital length of 
stay of greater than 7 days, is feasible. A sample size of 194 individuals (97 in each group) will be 
required for a two-tailed test at an alpha of 0.05 and power of 80%. All patients assigned to the pilot 
Prehab group completed the intervention, however, we are mindful that we will be recruiting frail, 
elderly patients who may have a higher dropout rate. Hence, we are estimating a 20% dropout rate and 
plan to recruit 244 individuals (122 in each study arm) to achieve an eventual sample size of 194 after 
dropout. 
5.4 Cost Analysis 
All patients in the study population will have a total cost calculated for their cardiac surgery hospital 
stay. This cost will be determined by tabulating cost of the Prehab intervention and different aspects of 
inpatient resource utilization for each study participant, and assign the best estimate of cost for each 
component. Pre- and post-operative hospital LOS on the hospital ward along with LOS in the cardiac 
surgery intensive care unit (CS-ICU) are expected to be the major drivers of a patient’s overall cost. A 
sensitivity analysis will also be performed to account for uncertainty in any of the costs by simulating 
several different scenarios, and developing a range of cost estimates for each patient. 
6 Data Management 
The data management and analysis will be undertaken by the St. Boniface Hospital/I.H. Asper 
Clinical Research Institute. The principal means of data collection and data processing will be via 
electronic data entry at each site. Data will be exported to the St. Boniface Hospital/I.H. Asper 
Clinical Research Institute stripped of any patient identifiers.  Each patient will be given a site and 
an anonymous unique study number.  
6.1 Site Monitoring 
Site monitoring will be performed by the site leads at their respective sites. 

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6.2 Data Recording and Document Retention 
De-identified data will be entered by each participating site into an electronic REDCap eCRF.  The data 
will be housed in a secure server located at the University of Manitoba Faculty Of Medicine.  Each site 
will only be able to access their own data and only the project manager and principal investigator will be 
able to view identifying data.  Each person having access to the REDCap software will be issued their 
own unique number generator key fob which will allow for audits of data entry.  All data collected will 
be by the study will be kept for a minimum of 7 years or as otherwise required by regulatory agencies. 
6.3 Data quality assurance 
Data entered by each site will be password-protected and the ability to access or change data prior to 
locking of the database will be restricted to the project manager.  Once initial data collection has been 
completed, missing data and implausible values will be identified using predetermined objective criteria, 
and queries resolved through direct communication with sites if required. This data cleaning process will 
be overseen by the PREHAB management committee. Treatment of outliers and missing data will be in 
accordance with the statistical analysis plan. 
6.4 Funding 
 
Canadian Institutes for Health Research (CIHR) 
 
Term and Budget Requested:  $619,784 (4-year term) 
7 Participating Sites 
The study will be conducted at four academic, tertiary care hospitals (St. Boniface Hospital, Winnipeg, 
MB,  Queen Elizabeth II Health Sciences Centre, Halifax, NS, Montreal Heart Institute, Montreal, QC, 
Quebec heart and lung institute, Saint-Foy, QC) and one non-academic hospital (Saint John Regional 
Health Centre, Saint John, NB) that perform cardiac surgery  

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8 Operations Structure 
8.1 Organization Chart 
 
8.2 Steering Committee 
The steering committee is responsible for all aspects of study design, management, analysis and 
publication of results. The steering committee will be comprised of the following individuals: 
Rakesh C. Arora (project leader), Todd Duhamel (co-site lead Winnipeg), Ansar Hassan (site lead Saint 
John), Nicholas Giacomantonio (site lead Halifax), Yoan Lamarche (site lead Montreal), Navdeep Tangri, 
Thang Ngoc Nguyen, Sarvesh Logsetty, Jitender Sareen, Colleen Metge, Hilary Grocott, Jo Anne 
Sawatzky, Kenneth Rockwood, Sean Bagshaw, Jonathan Afilalo, Jean-Francois Legare.  
8.3 Study management committee 
The study management committee is responsible for ensuring that the study meets the proposed 
milestones and deadlines.  The management committee will be comprised of the following individuals: 
Rakesh C. Arora (project leader), Todd Duhamel (co-site lead Winnipeg), Ansar Hassan (site lead Saint 
John), Nicholas Giacomantonio (site lead Halifax), Yoan Lamarche (site lead Montreal), Navdeep Tangri, 
Thang Ngoc Nguyen, Sarvesh Logsetty, Jitender Sareen, Colleen Metge, Hilary Grocott, Jo Anne 
Sawatzky, Kenneth Rockwood, Sean Bagshaw, Jonathan Afilalo, Jean-Francois Legare. 
8.4 Coordinating Centre 
The coordinating centre for this project will be the St. Boniface Hospital/I.H. Asper Clinical Research 
Institute located in Winnipeg, Manitoba. 
8.5 Principal Investigator/Project Lead 
The principal investigator for this project is Dr. Rakesh Arora. 
Dr. Rakesh Arora 
Email:  rarora@sbgh.mb.ca 
Work Phone: (204) 258-1031 
Steering 
Committee 
Management 
Committee 
Coordinating 
Centre 
St. Boniface 
General Hopsital 
Co-Site Lead - Dr. 
Arora 
Research Assistant 
B. Sc. (Med) 
Student #1 
B. Sc. (Med) 
Student #2 
Co-Site Lead - Dr. 
Duhamel 
Research Assistant 
Undergraduate 
Student #1 
Undergraduate 
Student #2 
Saint John Regional 
Health Centre  
Site Lead - Dr. 
Hassan 
Research Assistant 
QE II Health 
Sciences Centre  
Site Lead - Dr 
Giacomantonio.  
Research Assistant 
Research Fellow 
Project Leader 

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Work Fax:(204) 231-4624 
Institution: St. Boniface Hospital/University of Manitoba 
Department: Cardiac Sciences/Surgery 
CR3012-I.H. Asper Institute, St. Boniface Hospital 
369 Tache Ave., Winnipeg, MB, R2H2A6 
8.6 Regional PI’s/Site Leads 
St. Boniface General Hospital 
(Winnipeg) 
Dr. Rakesh Arora 
rarora@sbgh.mb.ca 
Dr. Todd Duhamel 
tduhamel@sbrc.ca 
Saint John Regional Health Centre 
(Saint John) 
Dr. Ansar Hassan 
ahassan@dal.ca 
Queen Elizabeth II Health Sciences 
Centre (Halifax) 
Dr. Nicholas 
Giacomantonio 
Nicholas.Giacomantonio@cdha.nshealth.ca 
Montreal Heart Institute 
(Montreal) 
Dr. Yoan Lamarche 
yoanlamarche@gmail.com 
University of Laval (Quebec heart 
and lung institute) 
Dr. Francois 
Dagenaise 
francois.dagenais@chg.ulaval.ca 
8.7 Research Coordinator 
The research/project coordinator will be responsible for the day-to-day coordination of activities 
between the three sites and will be based out of the coordinating center (St. Boniface General Hospital, 
Winnipeg). 
 
Ensuring ethics submissions are up-to-date and properly stored. 
 
Responsible for data handling and will liaise with the other two study sites. 
 
Will travel from Winnipeg to Halifax and St. John project sites to train the fee-for-service 
research staff located at those sites. 
 
Coordinate weekly teleconferences to support study implementation. 
 
Dissemination of the overall study 
 
PROJECT COORDINATOR AND SITE COORDINATOR RESPONSIBILITIES 
Phase 1: Planning 
 
Coordinate study planning activities 
 
Arrange stakeholder/researcher meetings 
 
Complete research ethics for the overall project and work with 
sites to complete local ethics applications/access committee 
submissions 
 
Orientate site personnel 
Phase 2: Implementation 
 
Coordinate study implementation for all sites. 
 
Make initial contact with potential. participants/screen/recruit 
in Winnipeg. 
 
Complete baseline, pre-operative and follow-up. 
measures/assessments on participants in Winnipeg. 
 
Data entry, to include baseline, pre-operative and follow-up 
measures; chart reviews; site data. 
Phase 3: Evaluation/ 
Dissemination 
 
Coordinate study evaluation/dissemination. 
 
Update review of literature. 

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 
Participate in knowledge dissemination. 
 
8.7 Research Assistants 
 
Site Coordinator #1 (Halifax, Nova Scotia): In order to implement the proposed study in Halifax, we plan 
to hire a 0.5 part time Site Coordinator for 2 years.  
 
Site Coordinator #2 (Saint John, New Brunswick): In order to implement the proposed study in Saint 
John, we plan to hire a 0.5 part time Site Coordinator for 2 years.  
 
Site Coordinator #3 (Montreal, Quebec): In order to implement the proposed study in Montreal, one 
year into study launch, we plan to hire a 0.5 part time Site Coordinator for 1 year.  
 
Site Coordinator #4 (Quebec City, Quebec): In order to implement the proposed study in Quebec City, 
two years into study launch, we will utilize their existing infrastructure for a minimum of 1 year.  
 
8.8 Students 
 
Master’s Graduate Student: Under the supervision of the Dr. Duhamel, the Graduate Student will work 
directly on the proposed project to: i) conduct a review of the literature to guide the development and 
refinement of the recruitment and screening approaches and to conduct the project evaluation; ii) work 
with the Program Coordinator to collect data by administering surveys/questionnaires and collect 
objective measures of physical activity; iii) liaise with the cardiac rehab sites to facilitate project 
outcomes.  
  
Postdoctoral fellow: Dr. Rockwood has recruited Dr. Roxanne Streniczuk to complete a postdoctoral 
training program under his mentorship and she will devote 25% of her time to this project. Both Drs. 
Rockwood and Duhamel will support her application for the Integrated and Mentored Pulmonary and 
Cardiovascular Training (IMPACT) program, a CIHR Strategic Training Program in Health Research 
training program at the St. Boniface Hospital. The overall objective of the IMPACT program is to create 
the next generation of investigators with the capacity to generate scientific knowledge and, equally 
importantly, with the skills and linkages to rapidly advance those discoveries to clinic and health care 
systems.  Notably, Dr. Todd Duhamel is the Program Director for the IMPACT program at the University 
of Manitoba; whereas, Dr. Rakesh Arora has specifically mentored several trainees within the program. 
As a result, Dr. Arora and Dr. Duhamel (Dalhousie) will co-mentor Roxanne Streniczuk (postdoctoral 
fellow).  
 
Dr. Arora will recruit two B.Sc. Med students from the Faculty of Medicine, University of Manitoba to 
work on the Prehab project. Additionally, Dr. Duhamel will recruit two undergraduate students from the 
Faculty of Kinesiology and Recreation Management, University of Manitoba for a Directed Studies 
Research Internship for course credit so they can work directly on the project. Dr. Giacomantonio will 

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also supervise a research fellow, Dr. Colin Yeung, at Dalhousie University. He will contribute 100% of his 
time to this project. 
9 Project Timeline 
April 2, 2014 to July 1, 2014 (Ethics Submission/Project Coordination) 
Obtain all relevant approvals from internal and external ethics boards. Assign duties and 
responsibilities to all individuals involved in the project. 
 
July 1, 2014 to October 1, 2014 
Begin holding focus groups to identify perceptions about physical activity in frail patients and 
their families. After an initial concentrated focus group session, we plan to continue ongoing 
sessions with key stakeholders as part of an integrated knowledge translation process. 
 
October 1, 2014 to December 1, 2015 (Patient Recruitment) 
 
Final goal is to recruit 244 total participants (122 individuals in each cohort). 
 
March 1, 2016 (Recruitment and Procedures Completed) 
Anticipated date by which all recruited patients will have undergone cardiac procedure and have 
been discharged from hospital. Primary outcome (hospital length of stay) is available.  
 
June 1, 2016 (All Patients Completed 3-Month Follow-Up) 
Anticipated date by which all recruited patients will be eligible for 3-month follow-up and 
quality of life questionnaire. 
 
March 1, 2017 (All Patients Completed 1-Year Follow-Up) 
Anticipated date by which all recruited patients will be eligible for 1-year follow-up and quality 
of life questionnaire. 
 
March 1, 2017 (Data Analysis and Manuscript Development) 
Preliminary data analysis will be conducted, drafts of manuscripts will be developed, iKT 
activities planned and performed. 
 
May 1, 2017 (Project Completion Date) 
All results have been finalized, manuscripts and abstracts have been submitted to various 
sources. Half-day symposium, joint with CACPR finalized. 
9.1 Research Deliverables and Milestones 
We anticipate the PREHAB study will require 3.5-years to complete (see Table below).  
9.2 Preliminary Project Schedule 
Timeframe 
Milestone 
Detail 
April – Oct., 
2014 
 
Continue with weekly 
teleconferences 
 
Finalization of DSMB terms 
of reference 
 
HREB protocol submissions 
to each of the sites 
Following a meeting at the Canadian Cardiovascular 
Congress in October, 2013, We have held a series of 
teleconferences to: (1) Create a HREB template based on 
the successful previous submissions (2) Begin the process 
of nominating a three member data safety and monitoring 
board (DSMB) panel to review all adverse/severe adverse 

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 
iKT elements 
events.  We will draft a formal terms of reference with a 
plan to have meetings every six months via teleconference 
with the principal investigator.  (3) Will begin holding focus 
groups to identify perceptions about physical activity in 
frail elderly patients and their families. After initial 
concentrated focus group sessions, we will continue 
ongoing sessions with key stakeholders as part of our iKT 
process. 
Oct., 2014 
Recruitment Begins 
We plan to allow for a 14-month recruitment period for 
initial randomization of patients (see Figure 5) 
Jan., 2015 
 
3-month follow-up begins 
This is will allow for the 8 week Prehab program, surgery 
and 12 week follow-up (to coincide with the follow-up visit 
with the patient’s surgeon). 
Oct., 2015 
 
1-year follow-up begins 
1-year follow up for exercise test and quality of life 
questionnaire. 
March, 
2016 
 
Recruitment and 
Procedures Completed 
Anticipated date by which all recruited patients will have 
undergone cardiac procedure and have been discharged 
from hospital. Primary outcome (hospital length of stay) is 
completely available.   
 
June, 2016   
All Patients Completed 3-
month follow-up 
Anticipated date by which all recruited patients will be 
eligible for 3-month follow-up and quality of life 
questionnaire.  
March, 
2017 
 
All Patients Completed 1-
Year Follow-Up 
Anticipated date by which all recruited patients will be 
eligible for 1-year follow-up and quality of life 
questionnaire. 
March, 
2017 – 
May, 2017 
 
Data analysis/proposed 
publications 
 
iKT elements 
 
Peer review grant 
preparation (CIHR) 
Data analysis will be conducted, drafts of manuscripts will 
be developed, iKT activities planned. Abstract preparation 
for presentation by trainees at scientific meetings. 
Initiation of planning with the CANCARE Society and CACR 
for educational sessions. 
10 Project Impact 
10.1 Project relevance and impact 
The geriatric population is one of the fastest growing demographics undergoing cardiac surgery 
in North America.(1)(2) With this, the geriatric syndrome, defined as a “constellation of symptoms and 
signs [that] describe the heterogeneous response of older adults to physiological and metabolic 
challenges,”(3) has become an important consideration in patients undergoing cardiac surgery. To date, 
no high-quality study has prospectively examined the impact of preoperative cardiac rehabilitation in 
the frail-elderly undergoing cardiac surgery and represents a noticeable knowledge gap. 
  
The PREHAB study is specifically aimed to improve the care and establish best practice in frail 
elderly patients undergoing high-risk cardiac surgery procedures through a rigorous evaluation of the 
utilization of an inter-disciplinary and multimodal patient optimization protocol. Importantly, we have 

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also planned for a detailed study analysis by key stakeholders at the health region level to determine 
optimal methodologies to implement this program following the completion of this investigation. 
Reducing anxiety, improving exercise capacity, promoting a healthy lifestyle that is durable (i.e. long-
lasting) and improving HRQoL in the elderly are the over-riding goals of this endeavour. This 
investigation directly fits with the Network’s Strategic Research Priorities of improving clinical outcomes 
in frail elderly patients. 
10.2 Contributions to HQP 
Training initiatives in HQP in the project will have a strong emphasis on clinical cardiovascular research. 
This focus will attract trainees interested in kinesiology and medicine. Two B.Sc. Medicine students, two 
Kinesiology undergraduate students, one Kinesiology M.Sc. trainee and two postdoctoral fellows will be 
will be mentored by Dr. Rakesh Arora, Dr. Todd Duhamel, Dr. Ken Rockwood and Dr. Nicholas 
Giacomantonio during this project.  
• 
Dr. Arora will recruit two B.Sc. Med students from the Faculty of Medicine, University of 
Manitoba (http://umanitoba.ca/faculties/medicine/research/bsc_med.html).  
• 
Dr. Duhamel will recruit two undergraduate students from the Faculty of Kinesiology and 
Recreation Management, University of Manitoba for a Directed Studies Research Internship 
(http://umanitoba.ca/faculties/kinrec/undergrad/directed_study.html) for course credit so they can 
work directly on the project. Dr. Duhamel will mentor Mr. Andrew Stammers to work on the proposed 
project if it is funded. Mr. Stammers has previously received an NSERC and a University of Manitoba 
Undergraduate Student Research Award ($12000). 
• 
Dr. Rockwood has recruited Dr. Roxanne Streniczuk to complete a postdoctoral training program 
under his mentorship and she will devote 25% of her time to this project. Both Drs. Rockwood and 
Duhamel will support her application for the Integrated and Mentored Pulmonary and Cardiovascular 
Training (IMPACT) program, a CIHR Strategic Training Program in Health Research training program at 
the St. Boniface Hospital. The overall objective of the IMPACT program is to create the next generation 
of investigators with the capacity to generate scientific knowledge and, equally importantly, with the 
skills and linkages to rapidly advance those discoveries to clinic and health care systems.   
• 
Dr. Giacomantonio will supervise a research fellow, Dr. Colin Yeung, at Dalhousie University. He 
has been awarded a Dalhousie research fellowship for $50,000/year for 2 years. He will contribute 100% 
of his time to this project. 
10.3 KT framework/platform 
A major component of the proposed project is to collect information that is appropriate to 
enable knowledge users to glean the information they need to inform new initiatives within their own 
organizations (i.e. knowledge-to-action).(91) The integrated (iKT) approach enhances the likelihood that 
the Prehab intervention will be implemented in the Canadian health care system and be sustainable 
over the long term. We have already taken the initial steps to implement an iKT approach to this 
application. Our intention of doing so was to include key stakeholders and potential knowledge users 
early in the process “to shape the research process by collaborating to determine the research 
questions, deciding on the methodology, being involved in data collection and tools development, 
interpreting the findings, and helping disseminate the research results”.(2) We have open relationships 
with the partners and key stakeholders needed to design and operate our study. Our ‘push’ efforts to 
link research to action will include patients/families (through shared decision-making 
efforts),(82)(83)(84) primary care providers, cardiac surgeons and cardiac rehab centres; while ‘pull’ 
efforts by our stakeholders will be enhanced by their involvement in the design and reporting of the 
study. Finally, we have included a solid evaluation of our efforts to link research to action (ref: Ellen M. 
WHO Knowledge Translation Framework for Ageing and Health. April 2012).  By using an iKT approach 

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and best practice evidence to inform a model of care for frail elderly persons needing cardiac surgery, 
the project will be able to influence the health system in a variety of ways. 
10.4 Project engagement 
Although we have already taken the initial steps to implement the iKT approach during the 
development of the grant application, once the project has begun we will convene a group of 
community stakeholders that include representatives from all the project sites, patients with higher 
levels of frailty who have previously undergone cardiac surgery and their family caregivers. Our 
intention of bringing these stakeholders together with the research team is to optimize the project 
intervention within the context of the patient experience prior to cardiac surgery, thereby facilitating 
‘pull’ efforts (WHO 2012). Moreover, this group will identify ways to address the barriers that may arise 
as the Prehab intervention is implemented at each site; this effort is aided by the climate for research 
that exists in our context. This iKT approach will inform our work plan, ensuring that the voices and 
experiences of stakeholders, patients and families have been considered. These stakeholders will also 
serve as the steering committee to provide input to refine the Prehab approach. 
 
 
 

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Tables 
Table 1 - How the PREHAB Study fits in the Technology Evaluation Framework 
 
 
 

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Table 2 - Characteristics of Included Studies In Frailty and Cardiac Surgery Systematic 
Review 
 
 
 

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Table 3 - Outcomes of Included Frailty and Cardiac Surgery Studies 
 
 
 

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Table 4 - Characteristics of “not frail” versus “frail” patients, according to the Modified 
Fried definition of frailty
 
 
 
 

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Table 5 - Intraoperative Variables 
 
Table 6 - Unadjusted Association of Frailty and Risk of Negative Postoperative Outcome 
 
 
 

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Table 7 - Comparison of baseline data between Standard care and Prehab groups 
 
 

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Table 8 - Comparison of operative characteristics between Standard care and Prehab 
groups 
 
 
 

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Table 9 - Seven step Formative Evaluation Plan
 
 
 

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Figures 
 
Figure 1 - An example of the journey faced by a “typical” frail elderly person undergoing cardiac surgery 
 
 

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Figure 2 - (Panel A) Flowchart of preliminary frailty study cohort recruitment over a 12-month period (July 9, 2012-July 31, 2013). 
Overall consent rate 77% with a study completion rate of 73%. 
(Panel B): Recruitment of patients over time (July 9, 2012 – July 9, 2013). Blue curve indicates patient recruited in the cardiac 
pre-admission clinic; Red curve the number of patients that have undergone their schedule cardiac surgery procedure. 

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Figure 3 - (Panel A): Total walking distance achieved by Standard care and Prehab patients during a 6-minute walking test. 
Values are mean ± standard error; Standard care n= 7; Prehab n=7. a different from baseline (p<0.05); # different from 
Standard care (p<0.05). Preop= one week pre-oeratively; Postop= three months post-operatively. 
(Panel B): Total time required by Standard care and Prehab participants to complete the 5-meter gait speed test. Values are 
mean ± standard error; Standard care n=7; Prehab n=7. adifferent from Baseline (p<0.05); #different from Standard care 
(p<0.05). Preop= one week pre-operatively; Postop= three months post-operatively. 
 
 
 

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Figure 4 - Proposed PREHAB Study Process Overview – Recruitment and Study Protocol 

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Figure 5 - A. Predicted Flow of Patients Per 14 Month Planned enrollment period.  B: Projected Study Timeline.  C: Timeline for 
Individual Objectives 
 
 

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Appendices 
Appendix I - Modified Fried Criteria (1-7) 
 
 
 

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Appendix II - Five item Geriatric Depression Scale (5-GDS) 
 
 
 

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Appendix III - Pilot Project Manuscript) 
 
 
 
 
 
 

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