Home-Based Exercise Program For Recovery After Transcatheter Aortic Valve Replacement: A Pilot Study
Phase: NA
Conditions: Aortic Valve Stenosis
Sponsor: Brigham and Women's Hospital

 
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Home-Based Exercise Program for Recovery 
After Transcatheter Aortic Valve Replacement: 
 
A Pilot and Feasibility Study Protocol 
 
Clinical Trial Registration: NCT02805309 
 
Update History 
 
Version 1 (12/14/2016) 
Version 2 (01/09/2017) 
Version 3 (02/14/2017) 
Version 4 (03/27/2017) 
Version 5 (05/01/2017) 
Version 6 (06/08/2017) 
Version 7 (08/21/2017) 
Version 8 (08/31/2017) 
Version 9 (09/23/2019) 
Version 10 (03/09/2021)

 
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TABLE OF CO\NTENTS 
0. UPDATE HISTORY ....................................................................................................................... 5 
1. OVERVIEW ................................................................................................................................... 6 
2. STUDY OBJECTIVES .................................................................................................................. 6 
2.1. PRIMARY OBJECTIVE ....................................................................................................................... 7 
2.2. SECONDARY OBJECTIVES ............................................................................................................... 7 
2.3. OTHER OBJECTIVES ........................................................................................................................ 7 
3. BACKGROUND ............................................................................................................................ 7 
4. STUDY POPULATION ................................................................................................................ 10 
4.1. INCLUSION CRITERIA ..................................................................................................................... 10 
4.2. EXCLUSION CRITERIA .................................................................................................................... 10 
5. ENROLLMENT ............................................................................................................................. 10 
5.1. SCREENING .................................................................................................................................... 10 
5.2. BASELINE ASSESSMENT OF FUNCTIONAL STATUS ....................................................................... 10 
5.3. BASELINE INTERVIEW AND MEDICAL RECORD REVIEW ................................................................. 11 
5.4. RANDOMIZATION ............................................................................................................................ 12 
6. STUDY INTERVENTION ............................................................................................................. 12 
6.1. HOME-BASED EXERCISE WITH COGNITIVE BEHAVIORAL INTERVENTIONS ................................... 12 
6.1.1. Schedule and contents of individualized exercise program ........................................... 12 
6.1.2. Cognitive behavioral interventions to improve adherence ............................................. 14 
6.1.3. Preventing and monitoring adverse events ...................................................................... 15 
6.1.4. Summary of tasks at each home visit ............................................................................... 15 
6.2. HOME-BASED EXERCISE ALONE ..................................................................................................... 15 
6.2.1. Schedule and contents of individualized exercise program ........................................... 15 
6.2.2. Preventing and monitoring adverse events ...................................................................... 15 

 
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6.2.3. Summary of tasks at each home visit ............................................................................... 16 
6.3. ATTENTION CONTROL EDUCATION INTERVENTION ....................................................................... 16 
6.3.1. Schedule and contents of attention control educational intervention ........................... 16 
6.3.2. Preventing and monitoring adverse events ...................................................................... 16 
6.3.3. Summary of tasks at each telephone call ......................................................................... 17 
7. FOLLOW-UP ASSESSMENT ..................................................................................................... 17 
7.1. ASSESSMENT SCHEDULE ............................................................................................................... 17 
7.2. BLINDING OF OUTCOME ASSESSORS ........................................................................................... 18 
7.3. MAXIMIZING RETENTION ................................................................................................................ 18 
8. STUDY ENDPOINTS ................................................................................................................... 18 
8.1. PRIMARY ENDPOINT ...................................................................................................................... 18 
8.2. SECONDARY ENDPOINTS .............................................................................................................. 19 
8.3. EXPLORATORY ENDPOINTS ........................................................................................................... 19 
8.4. TIMING OF OUTCOME ASSESSMENT .............................................................................................. 20 
9. SAFETY MONITORING AND ADVERSE EFFECTS ................................................................ 20 
9.1. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .................................................................. 20 
9.2. DATA SAFETY MONITORING PLAN ................................................................................................ 21 
10. STATISTICAL CONSIDERATIONS ......................................................................................... 24 
10.1. STATISTICAL ANALYSIS PLAN ..................................................................................................... 24 
10.2. SAMPLE SIZE JUSTIFICATION ...................................................................................................... 25 
11. HUMAN SUBJECT PROTECTION AND PROTECTION OF CONFIDENTIALITY ............... 25 
11.1. RISKS TO HUMAN SUBJECTS ...................................................................................................... 25 
11.2. ADEQUACY OF PROTECTION AGAINST RISKS ............................................................................ 25 
11.3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS .. 26 
11.4. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED .................................................................... 26 

 
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12. MULTI-CENTER PLAN ........................................................................................................ 26 
13. REFERENCES ........................................................................................................................... 27 
13. LIST OF APPENDIX MATERIALS ........................................................................................... 30 
 

 
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0. UPDATE HISTORY 
12/14/2016: The initial protocol was written for the Boston Claude D. Pepper Older American Independence 
Center Pilot Award. 
01/09/2017: The protocol was modified to include several cognitive-behavioral interventions to maximize 
the adherence to the exercise intervention.  Additional measures – self-efficacy and outcome expectation 
about exercise – were added.  The target enrollment was increased to 30 patients per each group.  After 
discussion with co-investigators and collaborators, the primary endpoint was changed from Short Physical 
Performance Battery (which measures specific functional tasks) to the patient-reported measure of Late 
Life Function Disability Instrument (which measures the actual performance of daily activities).  These mod-
ifications were made in preparation for the Boston Roybal Center Pilot Award Program. 
02/14/2017: The protocol was modified to have a 3-group comparison, home exercise with cognitive be-
havioral intervention, home exercise alone, and attention control education groups.  The sample size was 
changed to 20 participants in each group.  The aims and study interventions were modified accordingly.  
Data and Safety Monitoring Plan has been expanded.  These changes were made in response to the com-
ments from the Boston Roybal Center Pilot Award Program Review Committee. 
03/27/2017: Minor updates were made to the data safety monitoring plan in response to the Boston Roybal 
Center Pilot Award Program Committee. 
05/01/2017: Modifications were made per IRB request. 
06/08/2017: Minor updates were made to include details of interventions (e.g., individualized goal setting, 
weekly plan, and progression schedule) and the related forms (Appendices 1 and 2) based on the physical 
therapists’ input.  Pre-specified subgroup analysis was added.  The Clock drawing test was added to the 
baseline assessment for measurement of executive function. 
08/21/2017: New safety officer was designated per NIA requirement.  The intervention details were modified 
to allow flexible visit schedule to accommodate the participant’s medical appointments and personal pref-
erence; a RPE scale copy will be provided.  Time on study will be counted from the date of first intervention 
visit.  Before the intervention 1, 15 to 20-minute introduction was added to review the study intervention 
schedule with the participant. 
08/31/2017: Additional refinement in the intervention protocols and outcome assessment schedule was 
made. 
09/23/2019: Addition of BWH as a site for recruitment.  In July 2019, a problem occurred with the assess-
ment of the primary endpoint, LLFDI score.  The LLFDI-CAT software, which was originally developed in 
2008, was no longer compatible with the latest version of the operating system.  LLFDI paper version was 
used instead, but the items and assessment domains were not consistent between the two versions.  In 
addition, these changes were not immediately implemented by the outcome assessors, which resulted in 
missing measurements. 
03/09/2021: Since LLFDI-CAT scores were unavailable for most of the participants at 8 weeks, a post-hoc 
outcome measure, disability score, was analyzed. Analysis plan was revised for the disability score. 
 

 
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1. OVERVIEW 
With the increasing number of transcatheter aortic valve replacement (TAVR) procedures in multi-morbid 
frail older adults with aortic stenosis (AS), more high-quality evidence is needed to improve the postopera-
tive care of high-risk patients after TAVR.  Under the current model of care, TAVR patients continue to 
experience functional decline and disability despite symptomatic improvement.  Currently, there is no es-
tablished exercise intervention targeting both frailty and cardiac rehabilitation in older adults treated with 
transcatheter procedure. 
A pilot randomized controlled trial (RCT) of a home-based exercise intervention with or without cognitive 
behavioral interventions vs. attention control educational intervention will be conducted to evaluate its fea-
sibility in improving functional status and disability over 8 weeks in 60 older patients who are discharged 
home after TAVR from Beth Israel Deaconess Medical Center (BIDMC) or Brigham and Women’s Hospital 
(BWH).   
Following informed consent and baseline testing, the participants will be randomized in a 1:1:1 fashion (20 
patients per group) to receive either an individualized home-based exercise intervention with or without 
cognitive behavioral interventions or attention control educational intervention for 8 weeks.  The intervention 
will target balance, flexibility, strength, and endurance.  Exercises for the intervention group will be adopted 
from the National Institute of Aging (NIA) Go4Life exercise guide and modified to the participant's need and 
home environment.  The interventions will be conducted by a physical therapist at the participant's home.  
Upon discharge after TAVR, the participant will have 2 sessions per week for Weeks 1-2, 1 session per 
week for Weeks 3-4, and 1 session every other week for Weeks 5-8.  Cognitive-behavioral strategies will 
target self-efficacy, self-control, and positive outcome expectations of exercise to maximize adherence to 
the exercise program.  Participants in the attention-control arm will receive weekly telephone calls for 8 
weeks to learn general information about exercise and lifestyle tips.  Physical therapy outside the study is 
allowed per the participant’s physician.   
Participants will undergo measurements of physical function and disability at baseline, 4- and 8-weeks.  
The primary outcome is the Late Life Function and Disability Instrument – Computer Adaptive Test (LLFDI-
CAT), or the paper version (LLFDI).  As secondary outcomes, the change in physical function will be as-
sessed using the Short Physical Performance Battery (SPPB) and other performance measurements [re-
vised 1/9/2017].  Adverse events and adherence will be monitored during the intervention phase. 
The proposed research will provide essential information to design a larger clinical trial of a home-based 
exercise intervention that promotes independence and improves functional status and quality of life in multi-
morbid frail older adults undergoing TAVR through individualized risk assessment and interventions.  
  
2. STUDY OBJECTIVES 
The objective of this study is to determine the feasibility of an RCT comparing a home-based exercise 
intervention with or without cognitive behavioral interventions in older patients after undergoing TAVR.  We 
will evaluate the feasibility based on a) proportions of enrollment, refusal, and retention; b) adherence and 
potential barriers to exercise intervention; c) correlation of self-reported physical function and disability, 
LLFDI-CAT or LLFDI, vs. an objectively measurement of physical function, SPPB; and d) resources and 
costs of home visits and data management.  The information that we learn from this pilot study will inform 

 
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design of a larger, definitive RCT. 
2.1. PRIMARY OBJECTIVE 
The objective of this study is to conduct a pilot RCT of an 8-week, home-based exercise intervention with 
or without cognitive behavioral interventions vs. attention control educational intervention to evaluate its 
feasibility in improving physical function and disability over the 8-week period after TAVR.  We hypothesize 
that a home-based exercise program with cognitive behavioral intervention is more effective than home-
based exercise alone; home-based exercise program with and without cognitive behavioral intervention is 
more effective than attention control educational intervention in preventing decline in physical function and 
disability after TAVR, as measured by LLFDI-CAT or LLFDI.  
2.2. SECONDARY OBJECTIVES 
To examine the effect of the intervention on the following endpoints at 8 weeks after discharge: 
• 
Change in SPPB score 
• 
Change in 2-minute walk distance 
• 
Change in dominant hand grip strength 
• 
Adherence to exercise 
• 
Adverse events 
2.3. OTHER OBJECTIVES 
• 
To assess the correlation between the change in SPPB vs. the change in LLFDI-CAT or LLFDI 
score over 8 weeks after discharge. 
 
3. BACKGROUND 
Over 2 million older Americans are affected by AS and over 50% die within 2 years of symptom onset 
without treatment.  TAVR, a catheter-based surgical procedure, provides symptomatic and survival benefits 
in older adults who are considered high risk for surgical aortic valve replacement (SAVR).1-3  Symptomatic 
improvement has been reported in 80-90% of patients after TAVR,2,3 but it is unclear whether their functional 
status also improves.  Despite the high burden of frailty and disability in older adults undergoing TAVR, we 
found that functional status was infrequently measured in previous research; in the few studies that meas-
ured functional status, clinically important improvement was not consistently seen.4   
According to our unpublished data from an ongoing prospective study of older adults with AS who under-
went TAVR (N=59) or SAVR (N=47) between 2/2014-1/2015 at BIDMC and were followed for 6 months, 
we observed a modest correlation between the change in the New York Heart Association (NYHA) func-
tional class and the change in ADL (correlation: 0.33).  TAVR patients had higher prevalence of frailty 
phenotype (85% vs. 36%) and lower mean SPPB score (5.6 vs. 8.8) than SAVR patients.  Compared with 
SAVR patients whose ADL improved over 6 months, TAVR patients had ADL decline (Figure 1).  Our 
preliminary data highlights an urgent need for an intervention that promotes independence in TAVR pa-
tients.  

 
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The accumulating evidence suggests that multi-component exercise programs targeting balance, gait, 
strength, and endurance can improve mobility and physical function in frail older adults.5,6  Exercise is a 
core component of cardiac rehabilitation that reduces mortality and hospitalization and also improves the 
quality of life in younger patients with myocardial infarction or heart failure.7-10  Although most studies re-
quired on-site training, a home-based program appears to be as effective, with better adherence.11  The 
following studies (Table 1) provide supporting evidence. 
Table 1. Selected Studies of Home-Based Exercise Programs in Frail Older Adults 
Study 
Participants 
Intervention 
Outcome 
Jette 
(1998)12 
215 sedentary, func-
tionally limited older 
adults (107 interven-
tion group and 108 
control group) 
• Intervention: 6-month home-based exer-
cise program 
o 35-min video-taped program of 10 ex-
ercise routines x 3 times a week 
o 2 home visits by PT  
o Cognitive behavioral interventions: bi-
monthly exercise calendars, enhance 
positive attitudes and beliefs, discuss 
potential barriers, and review benefits 
of exercise 
o Bimonthly telephone monitoring 
• Control: continue normal routines 
• Follow-up: 6 months 
• 6-12% increased 
lower extremity 
strength 
• 20% improved tan-
dem gait 
• 15-18% reduction in 
physical and overall 
disability 
Gill 
(2002)13 
188 frail older adults 
in the community (94 
intervention group and 
94 control group) 
 
• Intervention: 6-month home-based exer-
cise program 
o 16 PT visits over 6 months 
o Exercise sessions 
o Removal of home safety hazards 
o Education on safety techniques 
• Control: health education 
• Follow-up: 12 months 
• Slower progression 
of ADL disability 
*
*
*
0
2
4
6
8
10
12
14
16
18
20
22
Functional Status Composite Score (0-22)
0
1
2
3
4
5
6
Postoperative Period (Month)
SAVR
TAVR
* P < 0.05 compared with baseline within each cohort
Figure 1. Functional status, measured in number of 
22 daily activities (higher number indicating better 
function), seems to improve after SAVR but to de-
cline after TAVR below their baseline. The data 
were derived from our ongoing prospective study of 
older adults with AS undergoing TAVR (N=59) or 
SAVR (N=47) in 2/2014-1/2015 at BIDMC. *p<0.05 
 

 
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Study 
Participants 
Intervention 
Outcome 
Matsuda 
(2010)14 
72 frail older adults 
(no control group) 
• Intervention: 6-week home-based exer-
cise program on strength, flexibility, gait, 
balance, and cardiovascular fitness 
o 1-hour weekly session 
o Graduate PT students 
o Cognitive behavioral interventions: 
weekly review of exercise log, discus-
sion of barriers, goal-setting 
• No control group 
• Follow-up: 6 weeks 
• Increased 3 reps on 
the biceps curl 
• Increased 2.4 reps 
on the chair stand 
• Increased 0.17 m/s in 
gait speed 
• Decreased 5.7 s on 
Timed-Up-and-Go 
• Increased 7 points on 
Self Efficacy Scale 
Molino-Lova 
(2013)15 
140 frail older adults 
with SPPB score <9 
after cardiac rehab  
(70 intervention group 
and 70 control group) 
• Intervention: 1-year home-exercise pro-
gram on strength, flexibility, balance, co-
ordination, and aerobic endurance 
o 2 classes by PT before discharge from 
cardiac rehab 
o Provided a booklet (no face-to-face 
contact) 
o 30-min session x 3/week 
• Control: aerobic exercise 
• Follow-up: 1 year 
• Intervention: SPPB 
improved from 
7.7 ± 1.4 to 9.0 ± 1.1 
• Control: no changes 
Latham 
(2014)16 
232 older adults who 
completed rehab after 
hip fracture (120 inter-
vention group and 112 
control group) 
• Intervention: 6-month home-based exer-
cise program 
o Initial 3 home visits by PT for teaching, 
followed by 3/week independent exer-
cise  
o Monthly telephone calls, DVD 
o Cognitive-behavioral interventions: 
overcoming fear of falls, setting specific 
goals, self-monitoring of progress 
• Control: attention control 
• Follow-up: 9 months 
• Intervention: SPPB 
improved from 6.2 ± 
2.7 to 7.2 ± 3.0 
• Improved the Activity 
Measure for Post-
Acute Care (AM-
PAC) score 
• Control: no change 
Abizanda 
(2015)17 
91 frail older adults in 
nursing homes (no 
control group) 
• Intervention: 12-week exercise and nu-
tritional supplement program 
o PT sessions 5 days a week 
o Nutritional supplement 2 cans/day 
• No control group 
• Follow-up: 12 weeks 
• 48% improved at 
least 1 point on 
SPPB at 12 weeks 
Despite the benefit of exercise, the proportion of older adults who are participating in regular exercise and 
physical activity is small.18  Barriers to participation include health problems, pain, fear of falling and injury, 
and negative expectations that exercise will not help their aging process.12,19-21  Previous research indicates 
that self-efficacy (i.e., one’s ability to engage in exercise) and self-control (i.e., one’s ability to regulate one’s 
emotions and behaviors) about exercise as well as positive expectation (i.e., belief that exercise will lead 
to desired outcomes) mediates the long-term adherence and beneficial response to an exercise program.22-
24  Therefore, cognitive-behavioral interventions to correct negative beliefs, promote self-efficacy, and en-
hance positive expectations  are essential for success of an exercise program. 
The accumulating evidence provides a strong rationale to conduct a pilot study to develop and test the 

 
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feasibility of a home-based exercise intervention combined with cognitive behavioral interventions in older 
adults undergoing TAVR. 
 
4. STUDY POPULATION 
4.1. INCLUSION CRITERIA 
Patients must meet all the following criteria to be included in the study: 
1) Age ≥65 years old 
2) Underwent TAVR 
3) Live within a 20-mile radius of the recruiting site  
4) Plan to be discharged home 
5) Able to provide informed consent 
4.2. EXCLUSION CRITERIA 
Patients will be excluded if they meet any of the following criteria:  
1) Stroke or any other medical disease that precludes participation in the exercise program 
2) Severe cognitive impairment, defined as Mini-Mental Status Exam score <15 
3) Concurrent enrollment in another clinical trial 
4) Lack of confirmation from the patient’s health care provider that the patient is medically safe to 
participate in the exercise program 
If the patient’s clinical condition changes after signing the consent form, and the patient is going to a 
rehabilitation or skilled nursing facility instead of home, we will dis-enroll these patients; outcomes and 
adverse events will not be collected from these patients. 
 
5. ENROLLMENT 
5.1. SCREENING 
We will contact the clinical team to obtain a list of patients who are planned for home discharge.  One day 
before the planned discharge date or on the day of discharge, patients will be approached in the hospital 
for eligibility and informed consent.  The screening process will continue until we enroll 60 patients.  Based 
on our experience at BIDMC, approximately 50% of TAVR patients are discharged home. 
5.2. BASELINE ASSESSMENT OF FUNCTIONAL STATUS 
Once the informed consent is signed, the participant will undergo geriatric assessment before hospital dis-
charge.  A trained research personnel will administer the following measures: 
• 
Mini-Mental State Examination (MMSE) or Telephone Interview for Cognitive Status (TICS) (10 

 
11 
minutes) (range: 0-30) (if in-person MMSE is not feasible) 
• 
LLFDI-CAT or LLFDI (5 minutes): LLFDI (range: 0-100) is a self-reported measure of activity limi-
tation and participation restriction for community-dwelling older adults.25-27  A shorter computerized 
adaptive version has shown comparable performance to the full version of LLFDI. 
• 
Dominant hand grip strength (2 minutes): average of 3 measurements (kg) 
• 
SPPB (5 minutes): A measure of lower extremity performance (range: 0-12) that includes the fol-
lowing components28-31: 
o 
Balance: side-by-side, semi-tandem, and tandem stand 
o 
Gait: 4-meter walk time (average of 2 measurements) 
o 
Strength: 5-chair stand 
• 
Two-minute walk test (3 minutes): a measure of endurance (meters walked) 
Based on validated cut-points,28-32 physical functional capacity will be categorized as very low, low, inter-
mediate, or high level of functioning (Table 2).   Based on the baseline functioning, an individualized home-
based exercise program will be designed (see the Study Intervention Section below). 
 
Table 2.  Physical Functioning Levels for Balance, Gait, Strength, and Endurance 
 
 
Very Low 
Low 
Intermediate 
High 
Balance 
Side-by-side 
<10.00 s 
≥10.00 s 
≥10.00 s 
≥10.00 s 
Semi-tandem 
<10.00 s 
<10.00 s 
≥10.00 s 
≥10.00 s 
Tandem 
<3.00 s 
<3.00 s 
3.00-9.99 s 
≥10.00 s 
Gait 
4-meter walk 
>8.70 s 
6.21-8.70 s 
4.82-6.20 s 
<4.82 s 
Strength 
Chair stand 
16.70-60.00 s 
13.70-16.69 s 
11.20-13.69 s 
<11.20 s 
Endurance 
2-minute walk 
<212 ft 
212-427 ft 
428-495 ft 
≥496 ft 
5.3. BASELINE INTERVIEW AND MEDICAL RECORD REVIEW 
Trained research personnel will interview the participant to obtain the following health information using the 
standardized case report form (see Appendix 1). 
• 
Demographic information: date of birth, gender, race, ethnicity 
• 
Social support: living status, support at home 
• 
Physical activity level: miles walked in the past week; stairs climbed in the past week 
• 
History of falls and use of assistive device 
• 
Pre-procedure NYHA class  
• 
Geriatric problems: hearing, vision, fatigue, insomnia, incontinence 
• 
ADL disability 
• 
Mini-Nutritional Assessment 
• 
Depression 
• 
Clock drawing test  
• 
Self-Efficacy for Exercise (SEE) scale (9 items)33 
• 
Outcome Expectation for Exercise (OEE) scale (9 items)34 
• 
The following information will be obtained from medical records (see Appendix 1). 
• 
Vital signs: blood pressure, heart rate, oxygen saturation, weight, height (at baseline assessment) 
• 
Dates of admission, surgery, discharge 
• 
Pre-procedure tests: echocardiogram, cardiac catheterization, laboratory test results 

 
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• 
Procedure characteristics: Society of Thoracic Surgeons predictive risk of mortality and of mortality 
or major morbidity, TAVR type, access route, VARC-2 complications35 
• 
Pre-procedure tests: echocardiogram, laboratory test results (last values before discharge) 
• 
Comorbid conditions and medications from discharge summary 
5.4. RANDOMIZATION 
The participant will undergo TAVR prior to randomization.  At the time of discharge, those who are being 
discharged home will be randomized in 1:1:1 ratio to home-based exercise with cognitive behavioral inter-
ventions vs. home-based exercise alone vs. attention-control education group using a computer-generated 
randomization sequence. 
 
6. STUDY INTERVENTION 
6.1. HOME-BASED EXERCISE WITH COGNITIVE BEHAVIORAL INTERVENTIONS 
6.1.1. Schedule and contents of individualized exercise program 
A study physical therapist will make a home visit 10-14 days after discharge to allow patients to adjust to 
their home environment and make follow-up doctors’ appointments.  When scheduling the first visit, the 
physical therapist will ask about the interim history (between discharge and the day of the scheduling call) 
to identify any medical condition changes.  At first visit, the physical therapist will spend 15-20 minutes 
reviewing the study goal; orienting the participant to the intervention and outcome assessment schedule; 
as well as the study staff they will interact with during the study period.  This time is not considered part of 
the study intervention.   
During the visit, the physical therapist (PT) will set individual goals and teach exercises designed to improve 
balance, flexibility, strength, and endurance.  Over an 8-week period, a PT will visit twice a week for Weeks 
1 and 2; once a week for Weeks 3 and 4; and every other week for Weeks 5 through 8 (on Weeks 6 and 8, 
respectively).  While adhering to this visit schedule is ideal, modification of the schedule is allowed to ac-
commodate the participant’s competing needs for doctor’s appointments and personal preferences, as long 
as the first 6 visits are in 4 weeks, the 7th visit in week 6, and the 8th visit in week 8.  [Revised 08/31/2017] 
The visits that did not happen within 4 weeks will not roll over to the second half of the intervention period.  
If the study physical therapist is unable to schedule/confirm the visit with the participant, they will call one 
more time during the week.  No more than 2 scheduling calls will be placed. 
Exercises targeting balance, flexibility, strength, and endurance will be adopted mainly, though not exclu-
sively, from the NIA Go4Life exercise guide booklet (source: https://go4life.nia.nih.gov/) and then modified 
based on the participant’s baseline physical function (Table 2) and home environment.  Sample exercises 
are shown in Table 3. 
Table 3. Sample exercises adapted from the NIA Go4Life Guide 

 
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Balance 
Flexibility (stretching) 
Strength 
Endurance 
• Stand on one foot 
• Heel-to-toe walk 
• Balance walk 
• Neck rotation 
• Shoulder 
• Shoulder and upper arm 
towel stretch 
• Upper body 
• Chest 
• Back 
• Ankle-modified to focus 
on hamstring stretch 
• Back of leg 
• Thigh 
• Hip, performed on the 
bed 
• Calf 
• Diaphragmatic breathing 
• Hand grip 
• Wrist curl 
• Front arm raise-seated 
• Side arm raise 
• Arm curl-seated 
• Seated row 
• Wall push-up 
• Elbow extension 
• Chair dip 
• Back leg raise 
• Side leg raise 
• Knee curl 
• Leg straightening 
• Chair stand 
• Toe stand 
• Walking 
At each home visit, the physical therapist will work with the participant to set and adjust daily exercise goals 
to improve balance, flexibility, strength, and endurance.  Exercise sessions will be 40 minutes in duration.  
The progression of exercise will be individualized as following: 
• 
Balance: based on baseline function as tested by SPPB and use of the Borg Rating of Perceived 
Exertion (RPE) scale, (as well as cardiac monitoring), the goal would be for patients to rate the 
exercise intensity between 11 and 13.  Progression would be adjusted based on this rating scale 
making the exercise either easier or harder.  The ability to perform the exercise with appropriate 
form and length would also determine the progression (i.e., stand on one foot with good form and 
without loss of balance with incremental time without touch support  until the participant is able to 
reach norms for age). 
• 
Strength: based on manual muscle test and baseline chair stand reps, initiate an appropriate weight 
where 8 reps would likely cause an RPE of 13-15 with appropriate cardiac response.  Progress to 
10-15 reps at 13-15 RPE, then progress to 2 sets of 10-15 reps at RPE 13-15, before increasing 
the weight. 
• 
Endurance: based on cardiac measures and baseline 2-minute walk test, adjust exercise intensity 
to maintain the goal of RPE of 11-13. 
• 
Flexibility: start with 10 second hold of each exercise and 3 reps, progress holding of stretch to 30 
seconds based on the goal RPE of 11-13 and cardiac status. 
The participants will be provided a copy of the RPE scale and instructed to exercise for at least 30 minutes 
daily focusing on upper and lower body exercises on alternating days, exercises for flexibility and balance 
daily, and walking daily.  By the end of the 8-week intervention period, the participant will receive the fol-
lowing exercises: 
• 
4 upper body strengthening exercises 
• 
4 lower body strengthening exercises 
• 
2-3 flexibility exercises, based on impairment 
• 
1 balance exercise, based on impairment and safety 
• 
Walking program 
• 
Diaphragmatic breathing 

 
14 
The study physical therapist will keep track of the participant’s progress, identified barriers, complaints, or 
any adverse events in a paper chart for each home visit.  Participants may receive physical therapy for 
medical needs outside the study if deemed necessary by their treating physician.  We will continue to weekly 
monitor use of outside physical therapy.  While the participant is receiving physical therapy outside the 
study, the study intervention will not be administered.  Once the outside physical therapy is complete, the 
study intervention will resume.  The study intervention will conclude after Week 8 according to the original 
schedule. 
6.1.2. Cognitive behavioral interventions to improve adherence 
A written exercise plan will be provided weekly.  Exercise images in the Go4Life guide booklet will be used, 
whenever appropriate.  Participants are instructed to do prescribed exercises for 30 minutes daily.  A diary 
will be given to track exercises (see Appendix 2).  The diary will include sections of 1) individualized goals; 
2) weekly plan; 3) weekly progress; 4) daily exercise tracking; and 5) adverse events.  The physical therapist 
will review the participant’s progress during each home visit, while also assessing for possible adverse 
events and offering specific safety tips for the future prevention of adverse events.  When necessary, exer-
cise intensity or progression will be modified.  To improve adherence, the following cognitive-behavioral 
strategies will be employed to improve self-efficacy, self-control, and outcome expectation for 20 minutes 
of each session: 
Week 1 
• 
Enhance positive attitudes and beliefs about exercise through discussion of benefits of exercise: 
Refer to the following sources: 
o 
NIA Go4Life guide page 6-7 (Why is physical activity such a big deal?) 
o 
NIA Go4Life guide page 11 (Benefits of exercise and physical activity) 
o 
NIA Go4Life guide page 13 (Specific types of exercise and their benefit) 
o 
NIA Go4Life guide page 31 (Building up the benefits) 
• 
Discussion of barriers to exercise: 
o 
Individualize to each participant 
• 
Individualized goal setting: 
o 
Complete the study form “Your Goals” sheet (Appendix 2 – Diary – Exercise-CBT Group) 
• 
Develop a detailed exercise plan on what, when, and where to conduct exercise: 
o 
NIA Go4Life guide page 20 (Write a plan to add exercise and physical activity to your life) 
o 
Complete the study form “Your Weekly Plan” sheet (Appendix 2 – Diary – Exercise-CBT 
Group) 
Week 2 through 8 
• 
Revise “Your Weekly Plan” every week 
• 
Self-monitor progress using exercise calendar 
o 
Review “Your Progress” sheet (Appendix 2 – Diary – Exercise-CBT Group) 
• 
Receive $10 rewards for achieving 30 mins of exercise daily for at least 5 of 7 days (or equivalent 
to 70% of days for the week) 
Prior to the intervention, physical therapists will be trained by an expert in Boston Roybal Center For Active 
Lifestyle Interventions (PI: Margie Lachman) who has developed and implemented a cognitive behavioral 
intervention protocol for exercise intervention for use by PTs without formal cognitive behavioral therapy 

 
15 
training. 
6.1.3. Preventing and monitoring adverse events  
Prior to each session, the physical therapist will review the health status of the participant, evaluate their 
home environment to identify safe areas for exercise, and teach safety tips and warning symptoms (e.g., 
chest pain or pressure, severe dyspnea, left shoulder or arm pain, indigestion, palpitations, lightheaded-
ness, dizziness, and headache).  Participants will be instructed to begin slowly at a low level of effort and 
gradually increase the intensity according to the therapist’s guidance.  Whenever available, we will engage 
caregivers or family members in supervising self-exercise.  Blood pressure, heart rate, and pulse oximetry 
will be monitored during the physical therapy sessions to assess the appropriateness of exercise. 
A research assistant who is unaware of the treatment assignment will monitor adverse events weekly using 
a standardized checklist (section 9; see Appendix 3).  Nonetheless, the participants may volunteer adverse 
events.  In addition, adverse events may occur during the exercise session.  In the case of adverse events, 
the physical therapist will evaluate the seriousness of the event and recommend the best course of action, 
in consultation with the PI or other licensed physician in the research team.  Participants and their caregiv-
ers will be instructed to activate the emergency medical service for serious adverse events that require 
immediate medical attention.  All adverse events will be reported to the PI.  If the severity of adverse events 
is high enough to require medical attention, we will obtain medical clearance from the participant’s physi-
cian.  Cardiac-related issues will require clearance from the participant’s cardiologist and non-cardiac is-
sues will require clearance from the participant’s primary care physician. 
6.1.4. Summary of tasks at each home visit 
A study physical therapist will be responsible for the following tasks at each home visit: 
• 
Reviewing the participant’s diary for progress since the last session and provide feedback. 
• 
Before exercise, checking vital signs (blood pressure, pulse, oxygen saturation) and checking for 
any change in health status (contraindication for exercise). 
• 
Providing an individualized exercise training session for 40 minutes  
• 
Providing a cognitive behavioral session for 20 minutes  
• 
Revising the individualized exercise plan, if necessary. 
• 
Reinforcing safety precautions and the procedure for emergency study contact. 
• 
Scheduling the next session  
6.2. HOME-BASED EXERCISE ALONE 
6.2.1. Schedule and contents of individualized exercise program 
The home visit schedule, exercises, and individualized progression protocol will be identical to those out-
lined in the home-based exercise with cognitive behavioral interventions in section 6.1.1.  Participants will 
be provided with daily exercise tracking sheet and adverse event reporting log.  However, the participants 
will not receive any cognitive behavioral interventions.  The duration of exercise session will be 40 minutes. 
6.2.2. Preventing and monitoring adverse events  

 
16 
Physical therapists will implement the same precautionary and monitoring actions to prevent adverse 
events during exercise as outlined in section 6.1.3.  Similarly, a research assistant who is unaware of the 
treatment assignment, will monitor adverse events weekly using a standardized checklist via telephone. 
6.2.3. Summary of tasks at each home visit 
A study physical therapist will be responsible for the following tasks at each home visit: 
• 
Reviewing the participant’s diary for progress since the last session and provide feedback. 
• 
Before exercise, checking vital signs (blood pressure, pulse, oxygen saturation) and checking for 
any change in health status (contraindication for exercise). 
• 
Providing Individualized exercise training session for 40 minutes  
• 
Revising the individualized exercise plan, if necessary. 
• 
Reinforcing safety precautions and the procedure for emergency study contact. 
• 
Scheduling the next session 
6.3. ATTENTION CONTROL EDUCATION INTERVENTION 
6.3.1. Schedule and contents of attention control educational intervention 
Participants randomized to the attention control group will receive written instruction on general exercise at 
the time of discharge from the hospital after TAVR as part of usual care (this information is given to all 
cardiac patients).  After discharge, a health care professional (MD investigator or physical therapist) will call 
the participant weekly for a period of 8 weeks to teach general tips about exercise and diet (Table 4 and 
Appendix 4) (source: https://go4life.nia.nih.gov/).  No recommendations for a specific exercise program 
will be made, except for walking 30 minutes daily or as tolerated.  Each telephone session will last approx-
imately 30 minutes and will cover the following 8 topics (4 exercise tips alternating with 4 healthy eating 
tips).  However, they may receive physical therapy outside the study if deemed appropriate by their treating 
physician.  This will be recorded. 
Table 4. Education Topics for Attention Control Group 
Schedule 
Topic 
Week 1 
Walking for Your Health 
Week 2 
What Does Healthy Eating Mean? 
Week 3 
Preventing Falls 
Week 4 
Overcoming Roadblocks to Healthy Eating 
Week 5 
Do Exercise and Physical Activity Protect the Brain? 
Week 6 
Making Smart Food Choices 
Week 7 
Exercising with Pain 
Week 8 
Choosing Healthy Restaurant Meals 
6.3.2. Preventing and monitoring adverse events 
Although the educational intervention for the attention control group does not recommend a specific exer-
cise program, it is possible that education on the beneficial effects of exercise and lifestyle may increase 
participants’ physical activity level.  Therefore, adverse events can occur in the participants in the attention 

 
17 
control group.  Although a research assistant who is unaware of the treatment assignment monitors adverse 
events weekly using a standardized checklist (section 9; see Appendix 3), the participants may volunteer 
adverse events during the educational intervention.  In this situation, the study physician or health care 
professional who makes the call will determine the seriousness of the event and recommend the best 
course of action, in consultation with the PI or a licensed physician in the research team.  Participants and 
their caregivers will be instructed to contact the emergency medical services for serious adverse events 
that require immediate medical attention.  All adverse events will be reported to the PI.    
6.3.3. Summary of tasks at each telephone call 
A health care professional will be responsible for the following tasks at each telephone call: 
• 
Deliver education intervention (30 minutes). 
• 
Reinforce safety precautions and knowledge about emergency study contact. 
 
7. FOLLOW-UP ASSESSMENT 
7.1. ASSESSMENT SCHEDULE 
Patients who were dis-enrolled due to rehabilitation discharge (this is an exclusion criterion) will no longer 
be included in the outcome follow-up.  After 4 weeks and 8 weeks of discharge (beginning of week 5 and 
week 9), all participants will be evaluated at home by a physical therapist (see Study Endpoint section 
below) (Table 5). Time on study will be counted from the date of first intervention visit or call.  This will be 
used to schedule the subsequent visit schedule and outcome assessment schedule. 
Table 5. Overview of Study Assessment BIDMC 
 
Study Procedures 
Research Personnel 
Place 
Recruitment 
NP (Cardiology)  
BIDMC 
Consent 
MD investigators 
BIDMC 
Baseline assessment 
RA 1 
BIDMC 
Medical record review 
RA 1 (review by an MD) 
BIDMC 
Randomization 
RA 2 
BIDMC 
Intervention 
• Intervention group 1: Physical therapist 1 (HSL) 
• Intervention group 2: Physical therapist 2 (HSL) 
• Attention control group: Physical therapist 3 (HSL) 
Home 
Home 
Telephone 
Outcome assessment 
• Performance Measures: Physical therapist 3 (HSL) 
• Self-Reported Measures and adverse events: Physical 
therapist 3 (HSL) 
Home 
 Home 
 
Table 6. Overview of Study Assessment at BWH 
Study Procedures 
Research Personnel 
Place 

 
18 
Recruitment 
MD/RN investigators 
BWH 
Consent 
MD/RN investigators 
BWH 
Baseline assessment 
RA 1 
BWH 
Medical record review 
RA 1 (review by an MD) 
BWH 
Randomization 
RA 2 
BWH 
Intervention 
• Intervention group 1: Physical therapist 1 (HSL) 
• Intervention group 2: Physical therapist 2 (HSL) 
• Attention control group: Physical therapist 3 (HSL) 
Home 
Home 
Telephone 
Outcome assessment 
• Performance Measures: Physical therapist 3 (HSL) 
• Self-Reported Measures and adverse events: Physical 
therapist 3 (HSL) 
Home 
Home 
7.2. BLINDING OF OUTCOME ASSESSORS 
A physical therapist who is unaware of the treatment assignment will perform the outcome assessment.  In 
the intervention group, this physical therapist will be different from the therapist delivering the intervention.  
Before the assessment, we will remind the participants not to reveal their group assignment to maintain 
blinding.  We will also keep track of blinding efficacy by adding a data element for the maintenance of 
blinding status in the Outcome Assessment form (Appendix 1). 
7.3. MAXIMIZING RETENTION 
To maximize retention, we will accommodate the participant’s personal preference in scheduling home 
visits and telephone calls.  We will provide a schedule and reminders for the next home visit (intervention 
group) and subsequent telephone calls (attention control group).  
 
8. STUDY ENDPOINTS 
8.1. PRIMARY ENDPOINT 
The primary endpoint is the change in the LLFDI-CAT or LLFDI score, a self-reported measure of physical 
functioning and disability.  The LLFDI-CAT has 2 domains: activity limitation domain and participation re-
striction domain.  The score ranges from 0 to 100, with higher values indicating better functioning or low 
disability.  This will be measured at 4 weeks and 8 weeks.  We will determine the effect of the intervention 
based on the change from baseline to 8 weeks.  In older adults at risk for mobility impairment, LLFDI was 
shown to have comparable psychometric properties and ability to predict meaningful changes in adverse 
health outcomes compared to performance-based measures.26 This will be measured at baseline and 4 
and 8 weeks after discharge. 
In July 2019, a problem occurred with the assessment of the primary endpoint, LLFDI score.  The LLFDI-
CAT software, which was originally developed in 2008, was no longer compatible with the latest version of 
the operating system.  LLFDI paper version was used instead, but the items and assessment domains were 
not consistent between the two versions.  In addition, these changes were not immediately implemented 

 
19 
by the outcome assessors, which resulted in missing measurements.  As a result, a disability score was 
calculated as an alternative post-hoc outcome measure (section 8.2.3).   
8.2. SECONDARY ENDPOINTS 
The following secondary endpoints will be measured at baseline and at 4 weeks and 8 weeks after dis-
charge.  We will calculate the change from the baseline to 8 weeks to determine the efficacy of the inter-
vention.   
1) Change in the SPPB: The SPPB is a simple, standardized, objective assessment of lower extremity 
function, which is highly correlated with frailty.28-31   
o 
Measurement: balance (0-4), gait speed (0-4), and chair stand score (0-4) (Table 6) 
o 
Range: 0-12 points 
o 
Interpretation: higher values indicate better function.   
o 
Clinically important change: 1 point36,37 
Table 6. Scoring of Short Physical Performance Battery 
Component Measurement 
0 
1 
2 
3 
4 
Balance 
Side-by-side 
<10.00 s 
≥10.00 s 
≥10.00 s 
≥10.00 s 
≥10.00 s 
Semi-tandem 
<10.00 s 
<10.00 s 
≥10.00 s 
≥10.00 s 
≥10.00 s 
Tandem 
<3.00 s 
<3.00 s 
<3.00 s 
3.00-9.99 s 
≥10.00 s 
Gait 
4-meter walk >30.0 s (unable) 8.70-30.00 s 
6.21-8.70 s 
4.82-6.20 s 
<4.82 s 
Strength 
Chair stand 
>60.0 s (unable) 16.70-60.00 s 13.70-16.69 s 11.20-13.69 s 
<11.20 s 
2) Change in 2-minute walk distance (meters): a test of endurance 
o 
Measurement: distance walked in 2 minutes 
o 
Range: >0 meters; 0-4 category (Table 2) 
o 
Interpretation: higher values indicate better endurance. 
o 
Clinically important change: 1 category increase 
3) Change in dominant hand grip strength (kg): a test of upper extremity strength 
o 
Measurement: use hydraulic hand dynamometer in dominant hand (average of 3 trials) 
o 
Range: >0 kg  
o 
Interpretation: higher values indicate better strength. 
o 
Clinically important change: 3 kg38 
4) Adverse events: see section 9.1. 
5) Adherence to the exercise program 
o 
Measurement: Proportion of days with completed daily task during the study period 
o 
Range: 0-1 (proportion) 
o 
Interpretation: higher values indicate better adherence. 
o 
Clinically important change: NA 
8.3. EXPLORATORY ENDPOINTS 
The following exploratory endpoints will be measured at baseline and at 4 weeks and 8 weeks after dis-
charge.  We will calculate the change from baseline to 8 weeks to determine the efficacy of the intervention. 
1) Change in MMSE or TICS: a measure of global cognitive function 
o 
Measurement: MMSE or TICS standard form (purchased from PAR, Inc) 

 
20 
o 
Range: 0-30 
o 
Interpretation: higher values indicate better cognitive function. 
o 
Clinically important change: ≥2 points based on reliable change index39 
2) Change in NYHA functional class (range: 1-4) 
o 
Measurement: a questionnaire to assess the extent of physical activity limitation due to 
heart failure 
o 
Range: 1-4 
o 
Interpretation: higher values indicate more severe limitations. 
o 
Clinically important change: ≥1 class 
3) Change in SEE 
o 
Measurement: Self-Efficacy Scale for Exercise33 
o 
Range: 0-90 
o 
Interpretation: higher values indicate higher self-efficacy. 
o 
Clinically important change: NA 
4) Change in OEE 
o 
Measurement: Outcome Expectation for Exercise34 
o 
Range: 1-5 
o 
Interpretation: higher values indicate stronger outcome expectations. 
o 
Clinically important change: NA 
8.3. POST-HOC ENDPOINT 
Because the primary outcome measure, LLFDI-CAT score, could not be analyzed, we calculated a disability 
score from 7 activities of daily living, 7 instrumental activities of daily living, and 8 Rosow-Breslaw and Nagi 
physical tasks.  The score indicates the number of activities that a person requires help from another person 
to perform.  It ranges from 0 (no disability) to 22 (total dependence), with a clinically important change of 1 
activity.  This measure has been used in previous studies.40  We will examine the correlation between the 
LLFDI baseline scores and the disability score (see section 10.1). 
8.4. TIMING OF OUTCOME ASSESSMENT 
The 4-week outcome assessment will take place during Week 5.  The 8-week outcome assessment will 
take place during Weeks 9-10.  Time on study will be counted from the date of first visit.  
 
9. SAFETY MONITORING AND ADVERSE EFFECTS 
9.1. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 For this study, the following standard adverse event definitions are used: 
• 
Adverse events: Any unfavorable and unintended sign, symptom, or disease temporally associ-
ated with the use of the study intervention, regardless of whether it is considered related to the 
study intervention. 
• 
Serious adverse event: Any adverse event that results in death, life-threatening experiences, 
hospitalization or prolonged hospitalization, persistent or significant disability or incapacity. 

 
21 
• 
Unanticipated problems: Any experience that 1) is unexpected in terms of nature, severity, or 
frequency, given the research procedures described in the protocol document and the characteris-
tics of the study population; 2) is related or possibly related to participation in the research; 3) 
suggests that the research places participants or others at a greater risk of harm than was previ-
ously recognized. 
Adverse events are graded according to the following scale: 
• 
Mild: An experience that is transient, and requires no special treatment.  The experience does not 
generally interfere with usual daily activities. 
• 
Moderate: An experience that is alleviated with simple therapeutic treatments.  The experience 
impacts usual daily activities. 
• 
Severe: An experience that requires therapeutic intervention.  The experience interrupts usual daily 
activities.  If hospitalization (or prolongation of hospitalization) is required for treatment, it becomes 
a severe adverse event. 
The study uses the following adverse event attribution scale: 
• 
Not related: The adverse event is clearly not related to the study procedures (i.e., another cause 
of the event is most plausible and/or a clinically plausible temporal sequence is inconsistent with 
the onset of the event). 
• 
Possibly related: An event that follows a reasonable temporal sequence from the initiation of study 
procedures, but that could readily have been produced by a number of other factors. 
• 
Related: The adverse event is clearly related to study procedures. 
A research assistant who is unaware of treatment assignment will interview participants via telephone 
weekly to assess adverse events using a standardized checklist (see Appendix 3).  If a participant reports 
adverse events during the intervention session (to a physical therapist or a health care professional), these 
adverse events will be reported to the PI on a weekly basis.   
Severe adverse events and unanticipated problems will be reported to the IRB, safety officer, and NIA 
within 24 hours.  In addition, all adverse events will be reported according to the IRB guidelines. 
9.2. DATA SAFETY MONITORING PLAN 
Patients who were dis-enrolled due to rehabilitation discharge (per exclusion criterion), will no longer be 
included in adverse event data collection.   
A. PARTICIPANT SAFETY 
A1. Potential Risks and Benefits for Participants 
The potential risks to study participants include a modest risk of physical harm, such as musculoskeletal 
pain, falls, or cardiac events from low-intensity exercise intervention.  Loss of confidentiality is another 
potential risk.  We do not anticipate any psychological, financial, or legal risks. 
The potential benefits to study participants include improvement in their physical function in response to 
our study intervention.  In addition, participants in the intervention group will receive a weekly incentive of 
$10 for achieving high adherence for 8 weeks.  All participants will be paid for $20 per outcome assessment 
at 4 and 8 weeks. 
A2. Adverse Event and Serious Adverse Event Collection and Reporting 

 
22 
Refer to the section 9.1 above. 
A3. Protection against Study Risks 
Informed consent process: A study team member will screen inpatient list of the cardiology service daily 
to identify eligible patients.  Age, home address, and procedure note will be reviewed for assessment of 
eligibility.  Potentially eligible patients will be approached 1-2 days prior to or on the day of discharge.  After 
explaining the study objectives, interventions, procedures, and potential risks and benefits, MD investiga-
tors will obtain a written informed consent.  Any questions from the participant or their proxy will be an-
swered.  This process will be documented in the patient’s medical record. 
Expected adverse events: The following adverse events can occur during study procedures or interven-
tions. 
• 
Fall and fall-related injury: the expected risk is low to moderate. 
• 
Musculoskeletal pain (new or worsening): the expected risk is moderate. 
• 
Cardiovascular events including angina, arrhythmia, myocardial infarction, heart failure, or stroke: 
the expected risk is very low. 
• 
Other symptoms including chest pain, dizziness/lightheadedness, dyspnea, palpitations, or syn-
cope: the expected risk is low. 
Protection against risk: Before obtaining consent, the research team will contact the patient’s attending 
physician to obtain medical clearance for the patient to participate in exercise.  To minimize physical harm, 
the physical therapist will adapt the exercise program according to the participant’s physical function, level 
of confidence, and home environment.  Prior to each exercise session, the therapist will encourage partic-
ipants to express any concerns about exercise and teach them safe exercise techniques.  In the case of 
adverse events, the physical therapist or the participant (or caregiver) will be instructed to contact a study 
physician for any adverse events and emergency medical services (EMS) for serious adverse events.  
These procedures will prevent or mitigate the consequences of adverse events.  If the participants are 
evaluated in the emergency department or hospitalized for any reason during the study period, the research 
team will contact the participant’s treating physician to obtain permission before resuming our study inter-
vention. 
B. INTERIM ANALYSIS 
Since this is a pilot study, no interim analysis will be performed.  Data analysis will be performed after study 
enrollment is complete. 
C. DATA AND SAFETY MONITORING 
The PI assures that informed consent is obtained prior to performing any research procedures, that all 
participants meet eligibility criteria, and that the study is conducted according to the IRB-approved research 
plan.  Because this is a pilot study, a formal Data and Safety Monitoring Board will not be formed; instead, 
a safety officer will be designated. 
Per NIA guideline, Dr. Houman Javedan, a geriatrician at Brigham and Women’s Hospital, will be a new 
safety officer who will be responsible for study oversight. 
C1. Frequency of Data and Safety Monitoring 

 
23 
Study data are always accessible for the PI to review.  The PI will review study conduct (number of potential 
patients screened, number of patients who provided informed consent, number of drop-out, and potential 
protocol deviations) on a weekly basis.  The PI reviews adverse events individually real-time and in aggre-
gate on a weekly basis.  The PI reviews serious adverse events in real-time.  The PI ensures that all protocol 
deviations, adverse events, serious adverse events, and unanticipated problems are reported to the IRB; 
serious adverse events and unanticipated problems that are likely to be related to the study intervention 
are reported to the safety officer and NIA.  The safety officer will review the study progress and status and 
adjudicate adverse events every 3 months.  The PI will annually prepare a report to NIA. Other Sites, BWH, 
will have all study conduct reviewed by the lead MD at their site. BWH is responsible to report all AEs to 
the PI at BIDMC. The PI will be responsible to ensure that all BWH protocol deviations, adverse events, 
serious adverse events, and unanticipated problems are reported to the IRB; serious adverse events and 
unanticipated problems are reported to the safety officer and NIA.   
C2. Content of Data and Safety Monitoring Report 
The content of the data and safety monitoring report will include accrual, baseline characteristics, efficacy 
data on primary and secondary outcomes, and adverse events. 
C3. DSMB/Safety Officer 
A formal Data Safety Monitoring Board will not be formed for this multi-center pilot study of behavioral 
interventions.  Instead, a physician who is not directly involved in this study will be identified for the safety 
officer role. 
C4. Conflict of Interest for DSMB/Safety Officer 
The safety officer should have no direct involvement with the study investigators or intervention.  The safety 
officer will declare any affiliations with pharmaceutical and biotechnology companies, and any other rela-
tionship that could be perceived as a conflict of interest related to the study and/or associated with com-
mercial interests pertinent to study objectives. 
C5. Protection of Confidentiality 
To protect confidentiality, data will be recorded in paper forms or using tablet computers.  Data at all sites 
will be entered into the secure REDCap database for data management and tracking purpose.  Paper 
records from all sites will be stored in a locked cabinet within the investigator’s office.  Only IRB-approved 
study personnel will have access to individually identifiable private information for the purpose of data col-
lection, contact of participants for home visits and telephone calls.  All research personnel will have up-to-
date training on human subject research. 
C6. DSMB/Safety Officer Responsibility  
• 
Review the research protocol, informed consent documents and plans for data safety and monitor-
ing 
• 
Recommend subject recruitment be initiated after receipt of a satisfactory protocol 
• 
Evaluate the progress of the trial, including periodic assessments of data quality and timeliness, 
recruitment, accrual and retention, participant risk versus benefit, performance of the trial sites, and 
other factors that can affect study outcome 

 
24 
• 
Consider factors external to the study when relevant information becomes available, such as sci-
entific or therapeutic developments that may have an impact on the safety of the participants or the 
ethics of the trial 
• 
Review study performance, make recommendations and assist in the resolution of problems re-
ported by PI 
• 
Protect the safety of the study participants 
• 
Report to NIA on the safety and progress of the trial 
• 
Make recommendations to the NIA and PI concerning continuation, termination or other modifica-
tions of the trial based on the observed beneficial or adverse effects of the treatment under study; 
and 
• 
Ensure the confidentiality of the study data and the results of monitoring 
 
 
10. STATISTICAL CONSIDERATIONS 
10.1. STATISTICAL ANALYSIS PLAN 
The analyst who will conduct statistical analysis will be blinded to the group assignment.  To ensure that 
randomization is properly conducted, we will check the balance in health status, including the measures of 
physical performance and functional status between the 3 treatment groups using analysis of variance, 
Kruskal-Wallis test, or Fisher’s chi-square tests. 
We will assess the Spearman correlation coefficient between the disability score and the LLFDI-CAT score 
from baseline. High correlation supports that the disability score can be a reasonable alternative post-hoc 
outcome measure.  
Aim 1 (home-based exercise combined vs. education): In analyses for primary endpoint (LLFDI-CAT or 
LLFDI score), secondary endpoints (SPPB score, 2-minute walk test distance, and dominant handgrip 
strength), and exploratory endpoints (MMSE or TICS score, NYHA class, SEE, and OEE), we will use a 
linear mixed effects model that models the outcomes as a function of time indicators (at 4 weeks and 8 
weeks) and treatment-by-time interaction terms, with a random intercept.  The treatment indicator is not 
included in the model because the baseline value of the outcome is assumed to be equal in an RCT.  The 
main treatment effect will be determined based on the treatment-by-time interaction term for 8 weeks (b4).  
The analysis will be performed according to the intention-to-treat principle. 
![#!] = &! + (")*+,#$$% ' + (()*+,#$$% ) + (*).,/)+,0) ∗)*+,#$$% ' + (').,/)+,0) ∗)*+,#$$% ) 
As a secondary analysis, we will include baseline variables that were not adequately balanced (standard-
ized difference >0.1) in the regression model.  As exploratory analysis, the Spearman correlation between 
the LLFDI-CAT or LLFDI change and the SPPB score change over 8 weeks will be examined.  [Revised 
06/08/2017] As a pre-specified subgroup analysis, we will examine whether the effect of the home-based 
exercise program combined is different by the baseline SPPB performance (median value to define the 
subgroup).   
Aim 2 (home-based exercise with cognitive behavioral intervention vs. home-based exercise alone): 
We will use a linear mixed effects model that models the outcomes as a function of time indicators (at 4 
weeks and 8 weeks) and treatment-by-time interaction terms, with a random intercept.  The treatment indi-
cator is not included in the model because the baseline value of the outcome is assumed to be equal in an 

 
25 
RCT.  The main treatment effect will be determined based on the treatment-by-time interaction term for 8 
weeks.  The analysis will be performed according to the intention-to-treat principle.  As a secondary analy-
sis, we will include baseline variables that were not adequately balanced (standardized difference >0.1) in 
the model.  We will assess the effect of cognitive behavioral intervention on the change in self-efficacy and 
outcome expectation over the 8-week period by using a linear mixed effects model that includes time indi-
cators (at 4 weeks and 8 weeks) and treatment-by-time interaction terms, with a random intercept. 
10.2. SAMPLE SIZE JUSTIFICATION 
Since a pilot study is designed to test the feasibility of recruitment and conduct of study procedures, this 
study is not powered to test a minimal clinically meaningful effect of an intervention.  Nonetheless, we 
provide power calculations under the assumption that the primary endpoint, LLFDI-CAT or LLFDI, has a 
standard deviation of 10 at a given time,26,41 low to moderate within-individual correlation ranging from 0.10 
to 0.40, and dropout rate of 20% in each group.  Type 1 error rate is set to 0.05.  The aim 1 of our study 
(home-based exercise vs. education) will have 66-83% power to detect an effect size of 10 (equivalent of 
1 standard deviation).  The aim 2 (home-based exercise with cognitive behavioral intervention vs. home-
based exercise alone) will have 53-71% power to detect an effect size of 10.  The estimation was done 
using GLIMMPSE (glimmpse.samplesizeshop.org).42  As this is a small exploratory study, we will not per-
form any interim analysis. 
Table 7. Power calculation 
SD of LLFDI-CAT/ LLFDI score 
Aim 1 (sample size: 40:20) 
Aim 2 (sample size: 20:20) 
Within-individual correlation 
0.10 
0.20 
0.40 
0.10 
0.20 
0.40 
Effect size* 10.0  
(equivalent to 1-SD) 
0.66 
0.72 
0.83 
0.53 
0.58 
0.71 
*Effect size is estimated using the difference of (LLFDI-CAT/ LLFDI) / MMSE or TICS score between the 
groups at 8 weeks. 
 
11. HUMAN SUBJECT PROTECTION AND PROTECTION OF CONFIDENTIALITY 
11.1. RISKS TO HUMAN SUBJECTS 
Because the study intervention involves low-intensity exercise, there is a modest risk of physical harm, such 
as musculoskeletal pain, falls, or cardiac events.  Alternative options to a home-based exercise program 
include center-based exercise programs or no exercise.  Center-based exercise programs may have an 
advantage of having professional supervision, but 2-3 weekly visits to the center are not practical in this 
frail population.  As we presented in our unpublished preliminary data (Figure 1), patients show decline in 
physical function and disability.  Low adherence to center-based exercise programs or no exercise will 
result in more progressive functional decline.  Loss of confidentiality is another potential risk.  We do not 
anticipate any psychological, financial, or legal risks. 
11.2. ADEQUACY OF PROTECTION AGAINST RISKS 
The physical therapist will adapt the exercise program according to the participant’s physical function, the 
level of confidence, and home environment.  Prior to each exercise session, the therapist will encourage 
participants to express any concerns about exercise and teach them safe exercise techniques.  In the case 

 
26 
of adverse events, the therapist or the participant (or caregiver) will be instructed to contact a study physi-
cian for any adverse events and emergency medical services for serious adverse events.  These proce-
dures will prevent or mitigate the consequences of adverse events.   
We will collect information on health status based on in-person and telephone assessments and review of 
medical records.  This information will be recorded on paper forms or using tablet computers.  Data at all 
sites will be entered into the secure REDCap database for data management and tracking purposes.  Paper 
records at all sites will be stored in a locked cabinet within the investigator’s office.  Only IRB-approved 
study personnel will have access to individually identifiable private information for the purpose of data col-
lection, contact of participants for home visits and telephone calls.  All research personnel will have up-to-
date training on human subject research. 
11.3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUB-
JECTS AND OTHERS 
The proposed research will provide essential information for the future design of a large clinical trial that 
examines the effect of a home-based exercise intervention on the functional status and quality of life in 
multimorbid frail older patients undergoing TAVR.  Under the current standard of care, TAVR patients con-
tinue to experience functional decline and disability.  Thus far, there is a paucity of rehabilitation interven-
tions that have proven effective.  As such, patients may benefit from our study intervention.  The potential 
benefit is likely to outweigh the modest risk of physical harms from exercise.  In addition, participants in the 
intervention group will receive a weekly incentive of $10 for achieving high compliance for 8 weeks.  All 
participants will be paid for $20 per outcome assessment at 4 and 8 weeks. 
11.4. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED 
With the increasing number of TAVR procedures in multimorbid frail older adults, more high-quality evi-
dence is needed to improve the postoperative care of high-risk patients after TAVR.  Currently, there is no 
established rehabilitation intervention for these high-risk patients.  Our proposed intervention, once con-
firmed in a large clinical trial, has great potential to influence the standard of care for future TAVR patients.  
We believe that this anticipated benefit outweighs the modest risk of physical harm to participants. 
 
12. MULTI-CENTER PLAN 
BIDMC will serve as a coordinating center. Currently, Brigham and Women’s Hospital is the only other site 
involved in this study. They will be recruiting patients from their center, consenting, and conducting baseline 
visits at BWH. Their physical therapy interventions will occur through HSL.BWH Research assistants will 
also conduct the follow-up phone calls for their enrolled participants. 
The plan for monitoring the research activities at the BWH site is as follows: 
1. Both BWH and BIDMC sites will have regular conference calls to review progress and enrollment, 
database entries, and AE reporting for the BWH site. As the overseeing site, BIDMC is responsible 
for maintaining protocols and study procedures, as well as informing BWH of new procedures as 
they occur. This will be done through monthly conference calls, as well as emails, to notify BWH of 
all study changes. 

 
27 
2. BWH personnel will be required to complete training in the study procedure and REDcap per 
BIDMC protocol. BWH will be required to enter all patient screens, participant’s data and other 
pertinent documentation for all study visits into REDcap. The overseeing PI has access to all infor-
mation that will be entered at the BWH site. 
3. AE reporting at BWH  will follow the same rules as those outlined for BIDMC . For mild, moderate 
events and severe AEs, the PI will be informed of deviations, unanticipated problems and adverse 
events, that occur at BWH by email as well as at a bi-weekly meeting with both BIDMC and BWH 
study teams in attendance. All reportable events occurring at BWH will be reported to the CCI in 
accordance with reporting requirements. All AEs that are recorded by the physical therapist from 
patients enrolled at BWH will be reported to the BIDMC PI by the physical therapist. 
4. The study monitors will be a research assistant and nurse from BIDMC. They will conduct on-site 
monitoring visits as indicated below and will also periodically review the BWH data in REDcap after 
10 patients are enrolled. Monitoring visits will verify that study protocols are followed (including 
adherence to inclusion and exclusion criteria and proper execution of study procedures), that 
proper consenting processes are used, verify all entries in REDcap by reviewing source documen-
tation and review records to ensure that all adverse events are reported in a timely manner to the 
study PI and the BIDMC IRB,as appropriate. 
Monitoring visits will occur at the following time points: 
• 
An on-site monitoring visit will be performed after the first participant is enrolled 
• 
An on-site monitoring visit will be performed after the subsequent 2-3 participants are enrolled. 
• 
Monitoring after initial enrollment will occur quarterly unless more frequent monitoring is warranted 
due to non-compliance with protocol. 
A written monitoring report will be provided to BWH and BIDMC CCI sites. 
 
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13. LIST OF APPENDIX MATERIALS 
• 
Appendix 1: Study Assessment Forms 
• 
Appendix 2: Diary to Record Weekly Exercise Plan and Progress Report 
• 
Appendix 3: Adverse Events Checklist

 
31 
Appendix 1. Study Assessment Forms

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
1
Interviewer 
Date 
MM / DD / YYYY 
I. SOCIODEMOGRAPHIC INFORMATION 
Name 
DOB 
MM / DD / YYYY 
MRN  
Gender 
Male / Female 
Race 
 American Indian/Alaska 
Native 
 African American 
 Asian 
 Native Hawaiian or other 
Pacific Islander 
 White 
 More than one race 
 Unknown 
Marital 
status  
 Married 
 Divorced 
 Widowed 
 Single 
 Unknown 
Lives in 
 Home 
 Assistive living facility 
 Nursing home 
 Others: 
 Unknown 
Ethnicity 
 Not Hispanic/Latino 
 Hispanic/Latino 
 Unknown 
Support 
 Informal support 
 Formal support (eg, VNA) 
 No support 
 Unknown 
II. HEALTH STATUS 
BP 
_______________ mmHg 
HR 
_______________ bpm 
O2 sat 
_______________ % 
Height 
_______________ inch 
Weight 
_______________ lbs 
BMI 
_______________ kg/m2 
In general, how would you rate your health? 
 Excellent 
 Good 
 Fair 
 Poor 
 Unknown 
During the last week, about how many miles did you 
walk outside your home? 
 # of miles:________ 
 Did not walk outside 
 Unknown 
During the last week, about how many flights of stairs 
did you climb? (1 flight = 10 steps) 
 # of flights:________ 
 Did not climb stairs 

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
2
 Unknown 
Did you have any falls in the past year? 
 Yes, # of falls:________ 
 No 
 Unknown 
Do you use an assistive device for walking? 
 Cane 
 Walker 
 None 
 Unknown 
Do you have SOB or fatigue when you … ? 
 do ordinary physical activity (class II) 
 do less than ordinary activity (class III) 
 are at rest (class IV) 
 Class I 
 Class II 
 Class III 
 Class IV 
 Unknown 
Do you have (condition)?  Poor eyesight 
 Lack of energy 
 Loss of bladder control 
 Poor hearing 
 Sleeping difficulty 
 None of the above 
III-1. LATE LIFE FUNCTION AND DISABILITY INSTRUMENT 
Administer LLFDI-CAT 
 Activity Limitation domain 
 Basic mobility and handling 
 Daily activities 
 Participation Restriction domain 
 Social roles 
 Instrumental roles 
Record scores 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 
III-2. DISABILITY 
Taking bath or shower 
 No difficulty 
 Difficulty, no help 
 Need help 
Using a toilet 
 No difficulty 
 Difficulty, no help 
 Need help 
Getting in/out bed 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking inside house 
 No difficulty 
 Difficulty, no help 
 Need help 
Dressing/undressing 
 No difficulty 
 Difficulty, no help 
 Need help 
Grooming 
 No difficulty 
 Difficulty, no help 
 Need help 
Eating 
 No difficulty 
 Difficulty, no help 
 Need help 

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
3
Using the telephone 
 No difficulty 
 Difficulty, no help 
 Need help 
Doing light housework 
 No difficulty 
 Difficulty, no help 
 Need help 
Doing heavy housework 
 No difficulty 
 Difficulty, no help 
 Need help 
Preparing own meals 
 No difficulty 
 Difficulty, no help 
 Need help 
Taking own medications 
 No difficulty 
 Difficulty, no help 
 Need help 
Handling own money 
 No difficulty 
 Difficulty, no help 
 Need help 
Shopping for groceries 
 No difficulty 
 Difficulty, no help 
 Need help 
Transportation 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking a flight of stairs 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking half a mile 
 No difficulty 
 Difficulty, no help 
 Need help 
Pushing a large object 
 No difficulty 
 Difficulty, no help 
 Need help 
Lifting 10 lbs 
 No difficulty 
 Difficulty, no help 
 Need help 
Crouching or kneeling 
 No difficulty 
 Difficulty, no help 
 Need help 
Reaching above shoulder  No difficulty 
 Difficulty, no help 
 Need help 
Handling small objects 
 No difficulty 
 Difficulty, no help 
 Need help 
IV. NUTRITION (MNA SCORING IN PARENTHESIS) 
Has food intake declined over the past 3 months due 
to loss of appetite, digestive problems, chewing or 
swallowing problems? 
 Severe decrease (0) 
 Moderate decrease (1) 
 No decrease (2) 
 Unknown 
Did you lose weight in the last 3 months? 
 Lost >6.6 lbs (0) 
 Does not know (1) 
 Lost 2.2-6.6 lbs (2) 
 No weight loss (3) 
 Unknown 
Mobility 
 Bed or chair bound (0) 
 Able to get out of bed but 
does not go out (1) 
 Goes out (2) 
 Unknown 
Has suffered psychological stress or acute disease in 
the past 3 months? 
 Yes (0) 
 No (2) 

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
4
 Unknown 
Neuropsychological problems 
 Severe dementia or 
depression (0) 
 Mild dementia (1) 
 No problems (2) 
 Unknown 
Body mass index (kg/m2) 
 <19 (0) 
 19 to <21 (1) 
 21 to <23 (2) 
 ≥23 (3) 
 Unknown 
V. SELF-EFFICACY SCALE FOR EXERCISE  
How confident are you right now that you could exercise three times per week for 
20 minutes if: 
Not confident 
Confident 
1. The weather was bothering you 
0 1 2 3 4 5 6 7 8 9 10 
2. You were bored by the program or activity 
0 1 2 3 4 5 6 7 8 9 10 
3. You felt pain when exercising 
0 1 2 3 4 5 6 7 8 9 10 
4. You had to exercise alone 
0 1 2 3 4 5 6 7 8 9 10 
5. You did not enjoy it 
0 1 2 3 4 5 6 7 8 9 10 
6. You were too busy with other activities 
0 1 2 3 4 5 6 7 8 9 10 
7. You felt tired 
0 1 2 3 4 5 6 7 8 9 10 
8. You felt stressed 
0 1 2 3 4 5 6 7 8 9 10 
9. You felt depressed 
0 1 2 3 4 5 6 7 8 9 10 
VI. OUTCOME EXPECTATION SCALE FOR EXERCISE 
Do you agree or disagree that exercise: 
Strongly 
agree 
Agree 
Neither 
Disagree 
Strongly 
disagree 
1. Makes me feel better physically 
1 
2 
3 
4 
5 
2. Makes my mood better in general 
1 
2 
3 
4 
5 
3. Helps me feel less tired 
1 
2 
3 
4 
5 
4. Makes my muscles stronger 
1 
2 
3 
4 
5 

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
5
5. Is an activity I enjoy doing 
1 
2 
3 
4 
5 
6. Gives me a sense of personal accomplishment 
1 
2 
3 
4 
5 
7. Makes me more alert mentally 
1 
2 
3 
4 
5 
8. Improves my endurance with my daily activities 
1 
2 
3 
4 
5 
9. Helps to strengthen my bones 
1 
2 
3 
4 
5 
VII. PSYCHOLOGICAL 
Over the past 2 weeks, how often have you been 
bothered by little interest or pleasure in doing things? 
 Not at all 
 Several days 
 More than half the days 
 Nearly every day 
 Unknown 
Over the past 2 weeks, how often have you been 
bothered by feeling down, depressed or hopeless? 
 Not at all 
 Several days 
 More than half the days 
 Nearly every day 
 Unknown 
MMSE score 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
Score: 
Total score (if <30): 
Clock drawing test (1 point for each component): 
1) Draw the outline of a clock face 
2) Put in all the numbers 
3) Set the hadns at ten past eleven 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
 Clock circle 
 Numbers in the 
correct order 
 Numbers in the 

BASELINE ASSESSMENT (updated: 06/16/2017) 
ID: ______________ 
 
6
correct spatial position 
 Insert two hands of 
the clock 
 Correct time 
VIII. PHYSICAL 
Dominant handgrip strength:  Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
 Left hand 
 Right hand 
1st: __ __ . __ kg 
2nd: __ __ . __ kg 
Chair stands 5 times 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
__ __ . __ sec 
Standing balance 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
side-by-side: __ __ . __ sec 
semi tandem: __ __ . __ sec 
full tandem: __ __ . __ sec 
4-meter walk speed 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
1st: __ __ . __ sec 
2nd: __ __ . __ sec 
2-min walk distance (feet) 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
__ __ __ feet 
 

CHART REVIEW (updated: 12/13/2016) 
ID: ______________ 
 
2
II. MEDICATIONS (FROM DISCHARGE SUMMARY) 
Alpha-blocker 
Angiotensin-converting 
enzyme inhibitor 
Angiotensin-receptor 
blocker 
Antianxiety 
Antiarrhythmic 
Anticoagulant  
Anticonvulsant 
Antidepressant – SSRI 
or SNRI 
Antidepressant – TCA 
Antidepressant – Others 
Antiplatelet 
Antipsychotic 
Antihypertensive – 
others (hydralazine, etc) 
Beta-blocker 
Bronchodilators (beta-2 
agonists) 
Calcium-channel blocker 
Cholinesterase inhibitor 
Digoxin 
Diuretic 
Incontinence drugs 
Inhaled corticosteroid 
Inhaled anticholinergic 
Inotrope 
Insulin 
Lipid-lowering – Statin 
Lipid-lowering – Non-
statin 
Memantine  
Nitrate 
NSAIDs 
Opioids 
Oral hypoglycemic – 
sulfonylurea 
Oral hypoglycemic – 
metformin 
Oral hypoglycemic – 
others 
Sedative - 
Benzodiazepine 
Sedative – Non 
benzodiazepine 
III. PREOPERATIVE TEST RESULTS (LATEST RESULTS) 
Test date 
MM / DD / YYYY 
Hemoglobin ___ . ___  g/L 
Creatinine 
___ . ___  mg/dL 
EGFR 
________ ml/min/1.73m2 
Albumin 
___ . ___  g/L 
HBA1C 
___ . ___ % 
Echo date MM / DD / YYYY 
LVEF 
________ % 
Aortic valve Area: __ . __ cm2 
Peak velocity: __ . __ cm/s 
Mean gradient: ____ mmHg 
Aortic 
regurgitation 
None 
Trace 
Mild 
Mild-moderate 
Moderate 
Moderate-severe 
Severe 
Unknown 
Mitral 
None 
Tricuspid 
None 

CHART REVIEW (updated: 12/13/2016) 
ID: ______________ 
 
3
regurgitation Trace 
Mild 
Mild-moderate 
Moderate 
Moderate-severe 
Severe 
Unknown 
regurgitation Trace 
Mild 
Mild-moderate 
Moderate 
Moderate-severe 
Severe 
Unknown 
Severe 
diastolic 
dysfunction 
Yes 
No 
Unknown 
Right 
ventricular 
dysfunction 
Yes 
No 
Unknown 
Cath date 
MM / DD / YYYY 
LVEF 
________ % 
Significant 
stenosis in 
native 
vessels 
No significant stenosis 
LM ≥50% 
LAD ≥70% 
LCX/OM ≥70% 
RCA/PDA/PL ≥70% 
Significant 
stenosis in 
grafts 
N/A (no graft) 
No significant stenosis 
IMA graft ≥70% 
Radial graft ≥70% 
Vein graft ≥70% 
Risk score 
ACC TAVR 
___ ___ . ___ % 
STS PROM 
___ ___ . ___ % 
STS PROMM ___ ___ . ___ % 
IV. POSTOPERATIVE TEST RESULTS (LATEST RESULTS) 
Test date 
MM / DD / YYYY 
Hemoglobin ___ . ___  g/L 
Creatinine 
___ . ___  mg/dL 
EGFR 
________ 
ml/min/1.73m2 
Albumin 
___ . ___  g/L 
HBA1C 
___ . ___ % 
Echo date MM / DD / YYYY 
LVEF 
________ % 
Central 
aortic 
regurgitation 
None 
Trace 
Mild 
Mild-moderate 
Moderate 
Moderate-severe 
Severe 
Unknown 
Paravalvular 
aortic 
regurgitation 
None 
Trace 
Mild 
Mild-moderate 
Moderate 
Moderate-severe 
Severe 
Unknown 

CHART REVIEW (updated: 12/13/2016) 
ID: ______________ 
 
4
V. POSTOPERATIVE COMPLICATIONS (VARC-2 DEFINITION) 
Myocardial infarction (MI) 
Peri-procedural MI (≤72 hr after 
the index procedure) 
Spontaneous MI (>72 hr after the 
index procedure) 
Stroke 
Ischemic 
Hemorrhagic 
TIA 
Bleeding 
Life-threatening or disabling 
bleeding 
Major bleeding 
Minor bleeding 
Acute kidney injury (AKIN 
classification) 
Stage 1 
Stage 2 
Stage 3 
Vascular access site and access-
related complications 
Major vascular complications 
Minor vascular complications 
Percutaneous closure device failure 
Conduction disturbances and 
arrhythmia 
Implant-related new or worsened 
cardiac conduction disturbance 
Persistent or transient high-degree 
AV block 
New permanent pacer implantation 
New-onset A fib or flutter 
New arrhythmia resulting in 
hemodynamic instability or 
requiring therapy 
Conversion to open surgery 
Unplanned CPB use 
Coronary obstruction 
Ventricular septal perforation 
Mitral valve damage or dysfunction 
Cardiac tamponade 
Endocarditis 
Valve thrombosis 
Valve malpositioning 
TAV-in-TAV deployment 
Prosthetic valve dysfunction 
Prosthetic aortic valve stenosis 
Prothesis-patient mismatch 
Prosthetic aortic valve 
regurgitation 
 

OUTCOME ASSESSMENT (updated: 06/08/2017) 
ID: ______________ 
 
1
Interviewer 
Date 
MM / DD / YYYY 
I. IDENTIFYING INFORMATION 
Name 
Assessment 
schedule 
 4 Week 
 8 Week 
Accidental un-blinding of the group assignment 
 Yes 
 No 
II. HEALTH STATUS 
In general, how would you rate your health? 
 Excellent 
 Good 
 Fair 
 Poor 
 Unknown 
During the last week, about how many miles did you 
walk outside your home? 
 # of miles:________ 
 Did not walk outside 
 Unknown 
During the last week, about how many flights of stairs 
did you climb? (1 flight = 10 steps) 
 # of flights:________ 
 Did not climb stairs 
 Unknown 
Do you use an assistive device for walking? 
 Cane 
 Walker 
 None 
 Unknown 
Do you have SOB or fatigue when you … ? 
 do ordinary physical activity (class II) 
 do less than ordinary activity (class III) 
 are at rest (class IV) 
 Class I 
 Class II 
 Class III 
 Class IV 
 Unknown 
III-1. LATE LIFE FUNCTION AND DISABILITY INSTRUMENT 
Administer LLFDI-CAT 
 Activity Limitation domain 
 Basic mobility and handling 
 Daily activities 
Record scores 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 

OUTCOME ASSESSMENT (updated: 06/08/2017) 
ID: ______________ 
 
2
 Participation Restriction domain 
 Social roles 
 Instrumental roles 
__ __ . __ __ 
__ __ . __ __ 
__ __ . __ __ 
III-2. DISABILITY 
Taking bath or shower 
 No difficulty 
 Difficulty, no help 
 Need help 
Using a toilet 
 No difficulty 
 Difficulty, no help 
 Need help 
Getting in/out bed 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking inside house 
 No difficulty 
 Difficulty, no help 
 Need help 
Dressing/undressing 
 No difficulty 
 Difficulty, no help 
 Need help 
Grooming 
 No difficulty 
 Difficulty, no help 
 Need help 
Eating 
 No difficulty 
 Difficulty, no help 
 Need help 
Using the telephone 
 No difficulty 
 Difficulty, no help 
 Need help 
Doing light housework 
 No difficulty 
 Difficulty, no help 
 Need help 
Doing heavy housework 
 No difficulty 
 Difficulty, no help 
 Need help 
Preparing own meals 
 No difficulty 
 Difficulty, no help 
 Need help 
Taking own medications 
 No difficulty 
 Difficulty, no help 
 Need help 
Handling own money 
 No difficulty 
 Difficulty, no help 
 Need help 
Shopping for groceries 
 No difficulty 
 Difficulty, no help 
 Need help 
Transportation 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking a flight of stairs 
 No difficulty 
 Difficulty, no help 
 Need help 
Walking half a mile 
 No difficulty 
 Difficulty, no help 
 Need help 
Pushing a large object 
 No difficulty 
 Difficulty, no help 
 Need help 
Lifting 10 lbs 
 No difficulty 
 Difficulty, no help 
 Need help 
Crouching or kneeling 
 No difficulty 
 Difficulty, no help 
 Need help 
Reaching above shoulder  No difficulty 
 Difficulty, no help 
 Need help 
Handling small objects 
 No difficulty 
 Difficulty, no help 
 Need help 
IV. SELF-EFFICACY SCALE FOR EXERCISE  
How confident are you right now that you could exercise three times per week for 
20 minutes if: 
Not confident 
Confident 
1. The weather was bothering you 
0 1 2 3 4 5 6 7 8 9 10 
2. You were bored by the program or activity 
0 1 2 3 4 5 6 7 8 9 10 

OUTCOME ASSESSMENT (updated: 06/08/2017) 
ID: ______________ 
 
3
3. You felt pain when exercising 
0 1 2 3 4 5 6 7 8 9 10 
4. You had to exercise alone 
0 1 2 3 4 5 6 7 8 9 10 
5. You did not enjoy it 
0 1 2 3 4 5 6 7 8 9 10 
6. You were too busy with other activities 
0 1 2 3 4 5 6 7 8 9 10 
7. You felt tired 
0 1 2 3 4 5 6 7 8 9 10 
8. You felt stressed 
0 1 2 3 4 5 6 7 8 9 10 
9. You felt depressed 
0 1 2 3 4 5 6 7 8 9 10 
V. OUTCOME EXPECTATION SCALE FOR EXERCISE 
Do you agree or disagree that exercise: 
Strongly 
agree 
Agree 
Neither 
Disagree 
Strongly 
disagree 
1. Makes me feel better physically 
1 
2 
3 
4 
5 
2. Makes my mood better in general 
1 
2 
3 
4 
5 
3. Helps me feel less tired 
1 
2 
3 
4 
5 
4. Makes my muscles stronger 
1 
2 
3 
4 
5 
5. Is an activity I enjoy doing 
1 
2 
3 
4 
5 
6. Gives me a sense of personal accomplishment 
1 
2 
3 
4 
5 
7. Makes me more alert mentally 
1 
2 
3 
4 
5 
8. Improves my endurance with my daily activities 
1 
2 
3 
4 
5 
9. Helps to strengthen my bones 
1 
2 
3 
4 
5 
VI. PSYCHOLOGICAL 
Over the past 2 weeks, how often have you been 
bothered by little interest or pleasure in doing things? 
 Not at all 
 Several days 
 More than half the days 
 Nearly every day 
 Unknown 
Over the past 2 weeks, how often have you been 
bothered by feeling down, depressed or hopeless? 
 Not at all 
 Several days 
 More than half the days 
 Nearly every day 
 Unknown 
MMSE score 
 Not performed 

OUTCOME ASSESSMENT (updated: 06/08/2017) 
ID: ______________ 
 
4
 Patient refused 
 Patient unable 
 Other: 
 Performed 
Score: 
Total score (if <30): 
VII. PHYSICAL 
Dominant handgrip strength:  Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
 Left hand 
 Right hand 
1st: __ __ . __ kg 
2nd: __ __ . __ kg 
Chair stands 5 times 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
__ __ . __ sec 
Standing balance 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
side-by-side: __ __ . __ sec 
semi tandem: __ __ . __ sec 
full tandem: __ __ . __ sec 
4-meter walk speed 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
1st: __ __ . __ sec 
2nd: __ __ . __ sec 
2-min walk distance (feet) 
 Not performed 
 Patient refused 
 Patient unable 
 Other: 
 Performed 
__ __ __ feet 

 
32 
Appendix 2. Diary

Your Goals
Short-term
What will you do over the next week or two that will help you 
make physical activity a regular part of your life?
1
2
3
ID:
Name:
Long-term
Write down at least two long-term goals.  
Focus on where you want to be in a year.
1
2
3

Your Weekly Plan
Week 1
Mon
Tue
Wed
Thur
Fri
Sat
Sun
Endurance
(where:                         )
Upper body strength
(where:                         )
Lower body strength
(where:                         )
Balance
(where:                         )
Flexibility
(where:                         )
ID:
Name:

Your Progress
Week 1
Week 2
Week 3
Week 4
Week 6
Week 8
Upper Body Strength
Count number of arm curls you can do 
in 1 minute
Lower Body Strength
Count number of chair stands you can 
do in 1 minute
Balance
Time you can stand on one foot 
without support for as long as possible
Flexibility
Note how far you can reach toward 
your toes until you feel a stretch
Endurance
Pick a ﬁxed course and see how long 
it takes you to walk that far
ID:
Name:

Track Your Activities
Week 1
Mon
Tue
Wed
Thur
Fri
Sat
Sun
What activity did you do?
How long did you do it?
Report in minutes
What activity did you do?
How long did you do it?
Report in minutes
Did you have a fall?
Answer yes or no
ID:
Name:

 
33 
Appendix 3. Adverse Events Checklist 

 
1 
Participant ID: 
Interview Date: 
MM/DD/YY 
Participant Name: 
Interviewer Name: 
Fall 
[  ] No 
[  ] Yes (provide the details below) 
Was there an injury? 
[  ] No 
[  ] Yes (provide the details below) 
Was medical attention (e.g. ED or office visit) sought? 
[  ] No 
[  ] Yes (provide the details below) 
Musculoskeletal pain 
(new or worsening) 
[  ] No 
[  ] Yes 
Location(s): 
Intensity (0 to 10): 
Was medical attention (e.g. ED or office visit) sought? 
[  ] No 
[  ] Yes (provide the details below) 
Cardiovascular 
events 
(new or worsening 
existing condition) 
[  ] No 
[  ] Yes (provide the details below) 
What was the diagnosis made by your doctor? 
[  ] Angina 
[  ] Arrhythmia (e.g., atrial fibrillation) 
[  ] Myocardial infarction 
[  ] Heart failure 
[  ] Stroke 
Other symptoms 
(new or worsening 
symptoms – without 
physician diagnosis) 
[  ] No other symptoms 
[  ] Chest pain 
[  ] Dizziness/lightheadedness 
[  ] Dyspnea – [  ] at rest or [  ] on exertion 
[  ] Palpitation 
[  ] Syncope (loss of consciousness) 
[  ] Other: _____________________ 
Details of the event 
Event date: MM/DD/YY 
Describe the event (e.g., location, duration, intensity, outcome). 
Action taken 
[  ] N/A – No adverse events 
[  ] PI notified – Date & time: MM/DD/YY HH:MM (Initial:       ) 
[  ] Clinical team notified – Date & time: MM/DD/YY HH:MM (Initial:       ) 

 
2 
ADJUDICATION OF ADVERSE EVENTS 
 
Date and time 
MM/DD/YY HH:MM 
Adjudication team 
Study physician: 
Independent non-study physician: 
Adjudication 
Is this event serious?  
(Adverse events that lead to death, life-threatening experience, hospitalization or 
prolonged hospitalization, persistent disability or incapacity, or receipt of medical or 
surgical treatment to prevent any of the listed outcomes) 
[  ] No 
[  ] Yes 
Is this event unexpected? 
(Adverse events that are not consistent with the risk information described in the 
investigational plan, in terms of nature, severity, or frequency) 
[  ] No 
[  ] Yes 
Is this event related to participation in the research? 
(Adverse events that are consequences of a) the intervention or interactions used in the 
research or b) the collection of identifiable private information in the research) 
[  ] No 
[  ] Unlikely 
[  ] Possibly 
[  ] Probably 
[  ] Yes 
Study participation 
Was the participant suspended from participation in the study? 
[  ] No 
[  ] Yes – Date: MM/DD/YY (provide the details below) 
Was the participant medically cleared to resume the study? 
[  ] No 
[  ] Yes – Date: MM/DD/YY (provide the details below) 
IRB notified 
[  ] Not immediately (reported in progress report) 
[  ] Immediately – Date & time: MM/DD/YY HH:MM (Initial:       ) 
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