Vest Prevention of Early Sudden Death Trial: Prevention of Sudden Death After Myocardial Infarction Using a LifeVest Wearable Cardioverter-defibrillator (Formerly VEST/PREDICTS)
Phase: NA
Conditions: Myocardial Infarction, Ventricular Dysfunction, Sudden Death, Ventricular Tachycardia, Ventricular Fibrillation
Sponsor: University of California, San Francisco

Vest Prevention of Early Sudden Death Trial: Prevention of Sudden Death After Myocardial 
Infarction Using a LifeVest Wearable Cardioverter-defibrillator (Formerly VEST/PREDICTS) 
NCT01446965 
Document Date: March 2, 2017 

VEST & VEST Registry – Summary of 
Revisions up to V3.2 
January 2018 Page 1 
 
VEST & VEST REGISTRY PROTOCOL 
SUMMARY OF REVISIONS up to V3.2 
 
Version 1.0 to Version 1.1 (12/10/08) 
 
1. Exclusion criterion for chest circumference changed from specific measurement to “Chest circumference too 
small or too large for LifeVest garment. 
 
Version 1.1 to Version 1.2 (2/2/2009) 
 
1. In the previous modification we changed the wording of the chest dimension exclusion criterion to “too small to 
too large for LifeVest garment” and added a footnote that included chest size up to 66 inches based on a 
recommendation of a representative of the manufacturer. The manufacturer now advises us that the footnote 
should be changed back to the ‘official’ upper limit of 56-inchesas changed in Table 1-1 on page 7. 
2. We have changed the wording to be consistent with the enrollment window of 7-days post-discharge so that 
enrollment activities are not all said to occur in the hospital: 
a. Top of Page 7 first paragraph, deleted ‘prior to discharge’. 
b. Middle of page 8, ‘Occurs’ replaced with ‘Begins’, ‘will’ replaced with ‘may’. 
3. Table 1-2 we changed wording to clarify that 
a. baseline testing may occur in hospital or clinic, 
b. ECG and EF (ejection fraction measurement are abstracted from admission records, and 
c. ECG and SAECG are measurements comprise one testing procedure , 
4. On page 15, Section 1.5.7, bottom of 2nd paragraph we clarify that the compliance reports are not printed and 
sent, but accessed via the VP study website. 
 
Version 1.2 to Version 1.3 (4/22/2009) 
1. Page 1-7: Table 1-1 
a. Inclusion criteria #2 , measurement interval for ejection fraction changed to 8 hours after MI and 8 
hours after a PCI. 
b. Exclusion criteria removed: Patients who have undergone CABG or other surgery within 30 days of 
screening 
2. Page 1-9 : Table 1-2 
a. Correction of typographical error to insert V7 (previously skipped in error) and subsequent visit 
numbers. 
b. Elimination of risk stratification testing at Visit 6 (Year2) including ECG/SAECG, Exercise Testing 
(TWA), 24° Holter and 6MW, BRS, and Local Labs 
3. Page 1-10: 
a. Narrative changed to remove all references to risk stratification testing during Year 2. 
b. All pages footnote: Version change from 1.2 to 1.3; and footnote date change to 4-22-09 
 
Version 1.3 to Version 1.3a (4/22/2009-same date as above) 
In April 2009, the CHR approved a minor modification that included the elimination of the third round of risk 
stratification testing at the 2-year visit (as had been suggested by the VEST/PREDICTS Executive Committee). 
However, during the May 12th meeting of the VEST/PREDICTS Steering Committee, the members voted to 
reinstate the third round of risk stratification testing. 
1. Page 1.7: Table 1-1 
2. Reinstatement of risk stratification testing at Visit 6 (Year2) including ECG/SAECG, Exercise Testing (TWA), 
24° Holter and 6MW, BRS, and Local Labs 
3. Page 1.10: Narrative changed to reinstate all references to risk stratification testing during Year 2. 
4. All pages footnote: Version change from 1.3 to 1.3a; and date change to 5-22-09. 

VEST & VEST Registry – Summary of 
Revisions up to V3.2 
January 2018 Page 2 
 
Version 1.3 and 1.3a to Version 2.0 (6/24/2009) 
 
Enrollment into the VEST/PREDICTS study was significantly lower than expected. Consequently, during meetings 
in May/June of 2009, the VEST/PREDICTS NIH-appointed Data Safety and Monitoring Board, Steering Committee, 
and Executive Committee members voted to approve three study modifications that include, 1) allowing separate 
entry into the VEST only or PREDICTS only components of the study while retaining participation into the combined 
VEST/PREDICTS study, 2) a reduction in the sample size for PREDICTS to 2400, and 3) an increase in the number 
of clinical sites implementing our protocol from 60 to 90. 
 
1. 
Relevant changes to the Protocol can be found on pages 1-7 to pages 1-10 where we present two tables and 
accompanying narrative summarizing different inclusion and exclusion criteria for the three entry options. The 
inclusion and exclusion criteria for ‘VEST/PREDICTS combined’ and ‘VEST only’ participation are the same, 
and have not changed from the most recent approved protocol version 1.3a. (as displayed in Table 1-1a on 
page 1-7). 
2. The modified inclusion and exclusion criteria for ‘PREDICTS only’ are displayed in Table 1-1b on page 1-8. For 
participants enrolling in PREDICTS only, we broadened the inclusion criteria to include patients ≤6 months from 
an MI (#1, Table 1-1b). Therefore the qualifying ejection fraction (EF) is either measured during the MI 
hospitalization, or if the patient presents outside of the 7-day post discharge window, the “most recent EF” 
before enrollment is the qualifying EF (#2, Table 1-1b). This change allows for a larger pool of patients and 
parallels what is done in practice through application of current ICD implantation guidelines. 
3. The modified exclusion criteria for ‘PREDICTS only’ excludes patients with an existing ICD, with a previous 
cardiac arrest, and with sustained ventricular tachycardia or ventricular fibrillation. However, patients are not 
excluded who have had prior CABG (after qualifying MI), paralleling current guidelines (3 months after CABG). 
4. Page 10:Table 1-2 has been modified to reflect different tests, visits, and data collected based on the three 
enrollment options. 
5. Page 14: The ICD or Reveal Implantation section was changed to allow for enrollment timing options in 
PREDICTS only. 
6. Page 21-22: The bottom paragraph on page 21 and top paragraph on page 22 were modified to reflect the 
reduction in sample size for PREDICTS and the concurrent changes in the analysis plan. 
 
Version 2.0 to Version 2.1 (1/29/2010) 
 
On December 3, 2009, VEST/PREDICTS (VP) Executive and Steering Committees and the NIH appointed DSMB 
approved a plan to 1) change the primary outcome in VEST from all-cause mortality to sudden death and, 2) 
extend the follow-up time in VEST to 3 months. These changes will allow VEST to be completed with a sample 
size of 1900 instead of the original target of 4506, and still provide valuable information on the effectiveness of a 
wearable defibrillator on reducing sudden death in the post MI period. 
Because this change in endpoint constitutes a departure from that which was originally reviewed, the NHLBI 
decided to discontinue support for VEST (they will continue support for PREDICTS) and ZOLL has agreed to 
provide sole support for the continuation of VEST with the above changes. The Protocol has been modified as 
follows: 
1. Protocol Version change from 2.0 to 2.1 
2. VEST Primary outcome changed from all-cause mortality to sudden death mortality 
3. VEST follow-up changed from 2 months to 3 months 
4. VEST sample size changed from 4506 to 1890 (1900) 
5. Changes in sample size calculations methodology for VEST 
6. Changes in Organization and Administration (reflecting NHLBI decision) 
7. DSMB membership list removed 
 
Version 2.1 to Version 3.0 (9/27/2011) 
 
As of March 1, 2010 enrollment in the PREDICTS arm of the study was stopped due to the withdrawal of funding 
from the NHLBI followed by the withdrawal of funding from Medtronic. After these decisions, ZOLL Lifecor 
Corporation decided to increase the amount of funding originally proposed to allow the Coordinating Centers to 
complete the VEST arm of the study and add a VEST Registry. Subsequently, the protocol was revised to reflect 
the needs of the VEST and VEST Registry. The changes were reviewed and accepted by the DSMB on September 
27, 2011 and on November 11, 2011, UCSF’s Committee on Human Research also approved the changes to the 
protocol as well as the consent forms 
 
The two major changes are as follows: 1) As of July 2011, the PREDICTS study follow-up is completed. Therefore, 
all PREDICTS-related text has been removed from the proposed new version of the protocol and 2) As suggested 

VEST & VEST Registry – Summary of 
Revisions up to V3.2 
January 2018 Page 3 
 
by the DSMB, the primary outcome was changed from sudden death mortality to sudden death and death due to 
ventricular arrhythmia. All references to the primary outcome have been revised, including Specific Aim 1. 
The protocol has been revised with the following changes: 
 
1. Protocol Version change from 2.1 to 3.0 
2. Page 3: Addition of VEST Registry 
3. Page 4: Addition of Aim 2: “To create a registry of VEST eligible patients for long-term follow-up to determine 
health and utilization outcomes. All VEST eligible patients will be offered participation in the VEST registry 
including those who previously participated in VEST.” 
4. Page 4: Stephen B. Hulley, MD, MPH has retired and the new DCC PI is Mark J. Pletcher MD MPH 
5. Page 5: Table 1 revised inclusion criteria to allow for patients with planned CABG and exclusions related to 
PREDICTS removed. 
6. Page 6: Visits related to PREDICTS were removed (e.g., 2-6 month testing, post-implantation visits. A 1-year 
visit was added to collect VEST registry data. 
7. Pages 8-9: Previously, stratification was conducted by revascularization status (PCI/No PCI). With the change 
in inclusion criteria for CABG, stratification will now be by “revascularization status (i.e., None/PCI/CABG)”. 
8. Page 11: Table 3, outcomes related to PREDICTS were removed 
9. Page 12: Additional detail was added to the VEST analysis plan. 
10. Page 13: Revisions were made to the plan for “Updating Sample Size”: 
11. Page 14: Biological specimens will no longer be collected, as this was PREDICTS-related. 
12. Page 14: Addition of VEST Registry in order to determine long-term outcomes in patients who are eligible for 
VEST, including those who enroll and complete the trial and those have previously participated in VEST. All 
patients in the VEST Registry will have yearly follow-ups to determine their vital status, their most recent EF, 
whether an ICD has been implanted and whether they have had any cardiovascular hospitalizations/events. 
These will be obtained by searching medical records and death indexes, and by interviewing participants by 
phone. 
13. Page 15: DCC now led by Mark Pletcher. 
14. Page 15: Reference to all previous industry partners except ZOLL removed 
15. Page 16: Reference to all previous industry partners except ZOLL removed 
16. Page 17: References to Medtronic removed 
Version 3.0 to Version 3.1 (12/20/2011) 
Administrative revisions: 
 
1. Protocol Version change from 3.0 to 3.1 
2. Page 3: Changes to Objective #2: To create a registry of VEST eligible patients for long-term follow-up to 
determine health and utilization outcomes. All VEST eligible patients study participants will be offered 
participation in the VEST registry including those who previously participated in VEST. 
3. Page 4 Changes to Specific AIM # 2: To create a registry of VEST eligible patients for long-term follow-up to 
determine health and utilization outcomes. All VEST study participants will be offered participation in the VEST 
registry including those who previously participated in VEST. 
4. Page 4: Removal of Jeff Olgin’s title “and Chief of the Cardiac Electrophysiology and Arrhythmia Service” 
5. Page 5, Table 1: Exclusion Criteria #5: “institution setting” changed to “skilled nursing facility” 
6. Page 6, Table 2: Test Reports, 12 Lead ECG and Local Labs: changed to V0 Enrollment only 
7. Page 6 Table 2: Test Reports, Echocardiography: changed to V0, V2 and Registry 
8. Page 7, Revisions made: VEST Registry Follow-up Telephone Call: Participants will be contacted by phone at 
least yearly to gather follow-up data. Participants will be asked about changes in medication, intervening 
hospitalizations, and simple follow-up questions regarding ICD/pacemaker device implantation. 
9. Page 7, Section 1.5.5 Interventions in VEST, Revisions made: Participants randomized to the LifeVest will be fit 
with the LifeVest ideally before they are discharged from the hospital or clinic, but the fitting may occur at the 
participant’s home within 7 days post discharge from the index MI. 
10. Page 9, Section 1.5.6 Randomization, Revisions made: Dr. Eric Vittinghoff replaced with “the Senior 
Statistician” 
11. Page 10, Outcome Adjudication: Dr. Joel Simon removed 
12. Page 13, Removal of: “These rules are in accord with guidelines suggested by Gould.” 
13. Page 13, Section 1.7 VEST REGISTRY, Revisions made: In order to determine long-term outcomes in patients 
who are eligible and enroll to participate in VEST, all patients in the VEST Registry will have at least yearly 
follow-up to determine vital status, most recent EF, whether an ICD has been implanted and whether they have 
had any cardiovascular hospitalizations/events. 
14. Page 15, Data Transmissions from Reading Centers, Laboratories, Removal of: “or ICD, or from a test 
producing digital data such as an echocardiogram, ECG, or Holter monitor” 

VEST & VEST Registry – Summary of 
Revisions up to V3.2 
January 2018 Page 4 
 
15. Appendix 1.B Steering Committee: Removal of old members and additions of new members including changes 
to titles 
16. Appendix 1.C Predictor Measures (selected): Removal of this appendix 
 
Version 3.1 to Version 3.2 (June 8, 2016) 
 
In October 2015, the VEST Data and Safety Monitoring Board (DSMB) reviewed the sample size re-estimation 
calculations after 1500 participants completed their Month 3 follow-up. The blinded interim analysis revealed that 
average LifeVest wear time was below target (i.e., below the estimated avg. of 17 hours per day, which was used 
for the original sample size calculations), but the composite event rate had been on target throughout the 
study. Due to the lower LifeVest average wear-time, which decreased the study’s current estimated power, the 
DSMB was concerned about a substantial likelihood of type II error. 
 
In March 2016, the DSMB recommended that the VEST sample size be increased by at least an additional 400 
participants, in order to maintain adequate study power. The DSMB also recommended that VEST study 
investigators and staff continue intense efforts to maintain or increase the recent improvement in wear-time rates, 
which is also essential to achieve adequate power. 
 
In April 2016, ZOLL agreed to provide support for the recommended increase of 400 participants and the VEST 
Steering Committee approved this amendment to the protocol on April 25, 2016. 
 
At the end of the trial, we will perform a National Death Index search for U.S. participants with unknown vital status 
to obtain data on the primary (Sudden death) and secondary (all cause mortality) study outcomes. Confirmation of 
VEST participant deaths is of vital importance, in order to reduce the risk of missing data bias which may impact the 
robustness of the final trial results. 
 
The Protocol has been modified with the following changes: 
 
1. Cover Page: Protocol Version Change to 3.2, Date change to June 8, 2016 
2. Cover Page: More Steering Committee Dates, DSMB Meeting Dates, and UCSF CHR approval dates added 
3. Page 6, Section 1.5.3 Recruitment Plan: The original sample size calculation estimated that 1900 participants 
would be enrolled in VEST (see Sample Size Calculations, below). Per protocol, an interim blinded sample size 
analysis was performed when 1,000 and 1,500 participants were enrolled, respectively. Per protocol, these 
analyses demonstrated the need to increase the sample size (see Appendix A). Therefore, approximately 2300 
participants will be enrolled in VEST (see Sample Size Calculations, below). 
4. Page 13, Section 1.5.12 Sample Size Calculations: Added text regarding Final sample size, DSMB 
recommendations, and Steering Committee approval. 
5. Page 13, Section 1.7.1 National Death Index Search at End of Trial: added aforementioned text 
6. Page 22, Reference: International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. 
Statistical Principles for Clinical Trials [E9]. 5 February 1998. 
7. Page 24, Appendix 1.b Steering Committee – removal of one Site PI 

VEST 
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6 
 
 
 
 
 
 
 
Vest prevention of Early Sudden death Trial (VEST) 
and 
VEST Registry 
 
PROTOCOL 
 
 
 
 
 
 
Version 3.2 
 
June 8, 2016 
 
 
Clinical Coordinating Center (CCC) 
Department of Medicine, University of California, San Francisco 
 
Data Coordinating Center (DCC) 
Department of Epidemiology and Biostatistics, University of California, San Francisco 
 
 
 
FUNDERS 
ZOLL, A108523 (VEST) 
 
 
 
Approvals 
Executive Committee (Date 10/15/07, 4/7/09, 5/12/09, 11/19/09, 8/31/11) 
Steering Committee (Date 11/12/07, 5/12/09, 11/20/09, 5/13/10, 10/29/10, 4/25/2016) 
DSMB (Date 1/3/08, 9/8/2008, 2/2/09, 3/16/09, 12/3/09, 6/1/10, 11/29/10, 9/27/11, 5/14/2012, 10/30/2013, 3/14/2014 
2/6/2015) 
 UCSF CHR/IRB (Initial Approval 6/28/07; Amendments approved 1/24/08, 2/24/08, 12/24/2008, 2/2/09, 4/22/09, 6/26/09, 
8/10/09, 2/10/2010; 3/3/2011; 3/6/2011; 3/21/2011; 7/14/2011, 11/11/2011, 11/29/2011, 7/12/2012, 7/11/2013, 7/23/2014, 
7/2/2015) 

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Table of Contents 
Page 
Protocol Summary 
3 
Part 1. Design 
1.1 
Specific Aims 
4 
1.2 
Background 
4 
1.3 
Protocol Principals 
4 
1.4 
Ethical Considerations 
4 
1.5 
Design and Methods 
1.5.1 
Overview 
5 
1.5.2 
Study Participants 
5 
1.5.3 
Recruitment Plan 
5 
1.5.4 
Schedule and Description of Visits 
6 
1.5.5 
Interventions in VEST 
7 
1.5.6 
Randomization 
8 
1.5.7 
Participant Retention 
9 
1.5.8 
Predictor Variables 
9 
1.5.9 
Outcome Variables 
9 
1.5.10 Adverse/Outcome Events 
11 
1.5.11 Analysis Plan for VEST 
12 
1.5.12 Sample Size Calculations 
12 
1.6 
Data Repository 
13 
1.7 
VEST Registry 
14 
1.7.1 
U.S. National Death Index Search at End of the Trial 
14 
 
Part 2. Coordinating Centers’ Plan 
2.1 
Organization and Administration 
2.1.1 
Coordinating Centers 
15 
2.1.2 
Committees and Governance 
15 
2.2 
Operations Manual, Forms 
16 
2.3 
Data Management System 
16 
2.4 
Computer and Data Security 
17 
2.5 
Training, Site Visits, and Quality Control 
17 
2.6 
Statistical Analysis and Dissemination 
18 
2.7 
Close Out 
18 
References 
19 
Appendices 
A. Table of Abbreviations 
21 
B. Steering Committee 
22 

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Protocol Summary 
 
Objective 
To conduct a multicenter, randomized controlled trial to test the hypothesis that a non-invasive wearable 
cardioverter defibrillator (WCD) will reduce sudden death and death due to ventricular arrhythmia in the first 90 
days following an MI in participants with left ventricular dysfunction (EF≤35%). 
To create a registry of VEST eligible patients for long-term follow-up to determine health and utilization 
outcomes. All VEST eligible patients study participants will be offered participation in the VEST registry 
including those who previously participated in VEST. 
 
Study Population 
Participants hospitalized with an MI with left ventricular ejection fraction (LVEF) of <35% who are at least 18 
years old. 
 
Study Design 
Randomized clinical trial 
 
Interventions 
LifeVest + Optimal post-MI/CHF treatment vs. Optimal post-MI/CHF treatment only 
(2/3 of participants will be randomized to receive the LifeVest) 
 
Primary Outcomes 
Sudden death and death due to ventricular arrhythmia 
 
Secondary Outcomes 
Non-sudden death mortality 
Cardiovascular mortality 
Total mortality 
Arrhythmic Death 
Non-Sudden Fatal MI 
Congestive Heart Failure Death 
Other Cardiac Death 
Stroke Death 
Other Non-Cardiac Death 
Indeterminate Cause of Death 
Non-Fatal MI 
Non-Fatal Congestive heart failure 
Non-Fatal Stroke/Transient Ischemic Attack 
Non-Fatal Atrial Fibrillation 
Inappropriate Shock – SVT 
Inappropriate Shock-malfunction 
Inappropriate Shock-oversensing 
Adverse Events 
Vest Compliance 
Quality of Life 
Resource Utilization/Cost 
Eventual ICD implantation (VEST registry) 
Change in EF (VEST registry) 
Mortality (VEST registry) 
CV hospitalizations (VEST registry) 
 
Study Duration 
90 days for the intervention trial (VEST) 
Long-term post-intervention follow-up (VEST registry) 

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PART 1. DESIGN 
 
1.1 SPECIFIC AIMS 
1. To conduct a multicenter, randomized controlled trial to test the hypothesis that a non-invasive 
wearable automatic defibrillator vest will reduce sudden death and death due to ventricular 
arrhythmia without a concomitant increase in non-sudden death mortality in the first 90 days 
following an MI in participants with left ventricular dysfunction (EF≤35%). This is the Vest prevention 
of Early Sudden death Trial (VEST). Participants will be randomized in a 2:1 fashion to receive optimal post- 
MI and CHF medical therapy plus a wearable defibrillator vest, or optimal post-MI and CHF medical therapy 
alone at the time of hospital discharge. 
2. To create a registry of VEST eligible patients for long-term follow-up to determine health and 
utilization outcomes. All VEST eligible patients will be offered participation in the VEST registry 
including those who previously participated in VEST. 
 
1.2 BACKGROUND 
While implantable cardioverter-defibrillators (ICDs) have had some impact in reducing the nearly 
500,000 annual sudden cardiac deaths (SCD) in the US2, our current treatment strategy is still limited. 
Recent studies have demonstrated a very high rate of sudden cardiac death in the first several months 
following a myocardial infarction (MI), particularly in participants with depressed left ventricular 
function. One study (DINAMIT) showed that implanting an ICD during this period reduced arrhythmic 
mortality, but did not reduce overall mortality.3 There are several potential reasons this study was 
negative including the possibility that the actual implant, anesthesia and DFT testing in the early post-MI 
period could adversely affect remodeling. Another possibility is that this was a select population of 
patients with low heart rate variability and thus more prone to a non-arrhythmic death. Nonetheless, 
because no study to date has demonstrated a mortality benefit of implanting an ICD within 40 days 
immediately after MI, the current practice is to wait at least 40 days after an MI. This leaves an 
unprotected, vulnerable period of increased sudden death risk prior to ICD implantation. VEST is 
designed to assess a potential strategy aimed at decreasing the high sudden death rate in this early post-MI 
period. 
 
1.3 PROTOCOL PRINCIPALS 
Jeffrey Olgin MD, Principal Investigator, Clinical Coordinating Center (CCC), Professor of Medicine and 
Chief of the Division of Cardiology, University of California, San Francisco (UCSF) 
 
Byron Lee MD, MAS, Co-Investigator, CCC, Associate Professor of Medicine in the Division of 
Cardiology and Attending Physician in the Cardiac Electrophysiology and Arrhythmia Service, UCSF 
 
Mark J. Pletcher, MD, MPH, Principal Investigator, Data Coordinating Center (DCC), Associate Professor of 
Epidemiology and Biostatistics, UCSF 
 
1.4 ETHICAL CONSIDERATIONS 
The study was peer-reviewed by the NIH and a grant was awarded that funded the first 3 years of the study. 
NIH funding ended in 2010. The UCSF Committee on Human Research has approved the study protocol and model 
consent form (Approval Number H43109-30941-01). The protocol has also been approved by the Steering 
Committee and the DSMB. Prior to initiation of recruitment of study participants, the study protocol and consent 
form as well as other important study documents will be reviewed and approved by the Institutional Review Boards 
of all participating clinical sites. Sites will be encouraged to use the study consent template unchanged, but we 
recognize that some IRBs may have varying requirements and the CCC will work with sites to ensure IRB approval 
of the study protocol and consent form. The CCC will ensure that all sites have up-to-date IRB approval, will track 
when sites are due for renewal and ensure that no enrollment occurs during any lapses in IRB approvals. 

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1.5 DESIGN AND METHODS 
1.5.1 
Overview 
VEST is a randomized, controlled trial to determine whether a wearable defibrillator vest (LifeVest, 
ZOLL, Pittsburgh, PA) reduces sudden death and death due to ventricular arrhythmia in the first 90 days 
following an MI. We hypothesize that a completely non-invasive, wearable defibrillator will decrease 
sudden death and death due to ventricular arrhythmia by decreasing arrhythmic mortality without an 
increase in non-arrhythmic mortality. 
The study timelines are shown in 
Figure 1. Participants hospitalized for an 
acute MI who meet the inclusion and 
exclusion criteria will be enrolled. They 
will then be randomized either to vest or 
no vest in a 2:1 fashion. Both groups will 
receive optimal post-MI and CHF 
medical therapy for their condition. 
 
1.5.2 Study Participants 
Participants hospitalized with an MI 
(or discharged after a recent MI) will be 
approached and evaluated for enrollment 
in the study. A standard definition of 
acute MI based on recently published 
criteria will be used:1 
• Detection of rise and/or fall of 
cardiac biomarkers (preferably 
troponin) with at least one value 
Table 1. VEST inclusion and exclusion criteria. 
INCLUSION CRITERIA 
EXCLUSION CRITERIA 
1. Patients identified in the hospital 
or within 7 days after discharge 
with a diagnosis of an acute MI 
(STEMI or Non-STEMI)1 
2. LV ejection fraction ≤35%, 
determined at the following time 
point: 
a) if no PCI within the first 8 
hours following the MI: 
≥8° after MI 
b) if acute PCI occurs within 8° 
of MI: ≥8° after PCI 
c) if CABG is planned (before 
or within 7 days of 
discharge), wait to enroll 
and then use the most 
recent assessment at 
least 48° post CABG. 
3. Age >18 years 
1. Existing ICD or indication for an 
ICD at the time of screening 
2. Existing unipolar 
pacemakers/leads 
3. Chronic renal failure requiring 
hemodialysis after hospital 
discharge 
4. Chest circumference too small or 
too large for LifeVest garment* 
5. Participants discharged to a 
skilled nursing facility with an 
anticipated stay > 7 days 
6. Pregnancy 
7. Inability to consent 
8. Any other condition or 
circumstance that in the 
judgment of the clinician makes 
the participant unsuitable for the 
study 
*as of this writing, garments are available for chest circumference of 26-56 
inches. 
above the upper limit of normal (ULN) for the particular lab, together with evidence of 
myocardial ischemia with at least one of the following: 
o Symptoms of ischemia 
o ECG changes indicative of new ischemia (new ST-T changes) or 
new left bundle branch block (LBBB); 
o Development of pathological Q waves in the ECG 
o Imaging evidence of new loss of viable myocardium or new 
regional wall motion abnormality. 
• Detection of rise and/or fall of 
cardiac biomarkers (preferably 
troponin) with at least one value 
above 3 x ULN for your lab in the 
setting of a percutaneous coronary 
intervention (PCI). 
Those who meet the inclusion criteria 
and do not meet any of the exclusion 
criteria will be eligible for randomization in 
VEST. Table 1 lists the specific inclusion 
and exclusion criteria for VEST. 
Figure 1. Overview of study timeline 

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1.5.3 Recruitment Plan 
The original sample size calculation estimated that 1900 participants would be enrolled in VEST (see 
Sample Size Calculations, below). Per protocol, an interim blinded sample size analysis was performed 
when 1,000 and 1,500 participants were enrolled, respectively. Per protocol, these analyses demonstrated 
the need to increase the sample size (see Appendix A). Therefore, approximately 2300 participants will be 
enrolled in VEST (see Sample Size Calculations, below). Sites will be chosen based on their success in 
other similar trials and access to adequate MI patient volumes. 
The CCC will oversee the recruitment effort and ensure that clinical sites actively recruit as many 
participants as possible. The CCC Project Director will act as a recruitment liaison with the sites, 
monitoring recruitment goals at each site and facilitating information sharing about successful recruitment 
strategies. If a center is found to be recruiting below goals, the CCC will arrange for those sites to 
exchange ideas and recruitment strategies with successful clinics, followed if appropriate by a site visit to 
assist the clinic in correcting any problems. Sites with continued recruitment difficulties may be closed 
before study termination. 
 
1.5.4 Schedule and Description of Participant Visits 
Each of the study 
participants will be first seen 
in the hospital during their 
admission for MI or after 
discharge in the clinic within 
the window of enrollment. 
They will then be followed 
with one phone call and one 
clinic visit. The schedule for 
testing and data collection is 
outlined in Table 2. The visit 
timeline and windows for 
visits are provided in Chapter 
3 of the Operations Manual. 
 
• Enrollment Visit (V0): 
Begins during the 
participant’s 
hospitalization for MI 
Table 2: Scheduled visits and data collection 
or within the window of enrollment after discharge. Participants who meet enrollment criteria will 
be asked to participate in the study after they are medically stable. After consent for VEST, they will 
be enrolled and randomized to vest or no vest. If randomized to vest, they may leave the hospital 
with the vest. The enrollment visit will involve collection of information and data abstracted from 
the hospital chart. 
• 1 Month Follow-up Telephone Call (V1): All participants will be contacted by phone to gather 
follow-up data. Participants will be asked about changes in medication, intervening hospitalization 
or visits to the emergency department, any problems with the vest (if randomized to the LifeVest) 
and a simple symptom checklist. 
• 3 Month Visit (V2): All participants will be seen for clinical data collection/final visit. Participants 
will be asked about changes in medication, intervening hospitalization or visits to the emergency 
department, any problems with the vest (if randomized to the LifeVest), and a simple symptom 
checklist. The patient’s most recent EF will be extracted from his/her medical record and assessment 
of qualification for primary prevention ICD will also be recorded. A Quality of Life survey will be 
DATA COLLECTED AND 
TESTING PERFORMED 
VISITS 
V0 
Post-discharge 
V1 
V2 
Registry 
Enrollment 
1 Month 
Phone 
3 Month 
Visit 
Screening and Medical History 
X 
Vital signs, discharge meds & 
diagnoses (from chart) 
X 
Symptom Checklist 
X 
X 
Medication Review 
X 
X 
X 
Medical Care Utilization 
X 
X 
X 
Vital Status 
X 
X 
QOL Survey 
X 
Test Reports 
• 12 lead ECG 
• Local Labs 
From Medical 
Record 
• Echocardiography 
From Medical 
Record 
From Medical 
Record 
From Medical 
Record 
Home Monitoring 
 LifeVest 
upload baseline at 
fitting 
3 times in 1st week, 
then weekly 

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mailed to the participant prior to this visit for self-administration and returned to the clinical site 
during this visit. 
• VEST Registry Follow-up Telephone Call: Participants will be contacted by phone at least yearly to 
gather follow-up data. Participants will be asked about changes in medication, intervening 
hospitalizations, and simple follow-up questions regarding ICD/pacemaker device implantation. 
Continuous Participant Monitoring (during the study period: V0-V2) 
In addition to the visits described above, participants randomized to LifeVest will have continuous 
remote monitoring via the LifeVest. 
 
Monitoring Capabilities and Data Collection from LifeVest: The LifeVest performs constant ECG 
monitoring while it is worn. It records all ventricular tachyarrhythmias that last more than 15 seconds and 
asystolic events (<20 beats per minute). Bradyarrhythmias (<40 bpm) are logged but no ECG is recorded. 
It also compiles compliance data by recording the amount of the time the LifeVest is worn each day. This 
data will be uploaded via modem and phone line. After initial setup, the coordinator or fitter (from ZOLL 
Lifecor) will upload the participant’s baseline data, then the participant will upload (from home) every 
other day for a total of 3 times during the first week and then subsequently on a weekly basis. The DCC 
will notify enrolling sites if participants are not sending scheduled transmissions. The enrolling sites can 
then contact participants to discover problems and encourage compliance. Sites with persistent or 
numerous poorly compliant participants will be visited and their staff re-trained. 
 
The participant’s compliance to the visit schedule will be continuously monitored on the study 
website by clinical site. The CCC will review visit compliance reports with the clinical sites on the 
Quality Control Committee conference calls/meetings to identify problems and recommend corrective 
action. If a participant misses a scheduled visit, clinic staff will contact him/her immediately to review the 
reasons for the missed visit, to identify any barriers that can be corrected, and to reschedule the visit. 
 
1.5.5 Interventions in VEST 
Participants will be randomized in a 2:1 fashion to either receive optimal post-MI and CHF medical 
therapy plus a wearable defibrillator (LifeVest) or optimal post-MI and CHF medical therapy alone for 90 
days. Participants randomized to the LifeVest will be fit with the LifeVest ideally before they are 
discharged from the hospital or clinic, but the fitting may occur at the participant’s home within 7 days 
post discharge from index MI. 
 
Compliance: Prior to consent to participate in the study, potential participants may be shown the 
LifeVest and given an opportunity to try it on. Participants will be told that they will be expected to wear 
the LifeVest for at least 23 hours a day for 3 months. Site coordinators will be trained on how to use the 
LifeVest and will help teach participants how to use the LifeVest properly to enhance compliance. 
Participants will be fully trained on how to put the LifeVest on and off, and how to temporarily disable 
the LifeVest by pushing a button to prevent inappropriate or premature shock. Additionally, participants 
will be trained how to maintain the LifeVest and determine if it is functioning normally as well as how to 
transmit data from the LifeVest monitor via the integrated modem over a phone line. Participants, 
regardless of group assignment, will receive optimal medical therapy based on current AHA/ACC 
Guidelines unless there is a contraindication7, 8. 
Participants will be urged to wear the LifeVest continuously after hospital discharge for at least 3 
months (or until ICD implantation). They will be instructed to take the LifeVest off only for bathing or 
showering. Participants will send data from the LifeVest monitor via modem 3 times a week for the first 
week and on a weekly basis thereafter. These data will include the compliance of wearing the LifeVest, 
Holter data, arrhythmia occurrence and shocks (delivered and aborted). Site coordinators will contact 
participants who don’t transmit on schedule or who wear the LifeVest <20 hours per day for 2 

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consecutive days by phone to discuss any problems participants might be experiencing with the purpose 
of obtaining excellent overall compliance rates. For sites with poor compliance rates, the following 
remedial actions will be taken: 1) discussions with site coordinator; 2) engagement of ZOLL Lifecor staff 
and site visit for coordinator training, if needed; 3) engagement of ZOLL Lifecor staff for fitting of 
participants. 
Blinding to treatment assignment: Participants and clinicians will not be blinded to treatment 
assignment (LifeVest versus no LifeVest). Since the primary outcome in VEST is sudden death and death 
due to ventricular arrhythmia, it is unlikely that this outcome would be significantly affected by either 
participant or clinician knowledge of treatment assignment. 
Blinding to arrhythmias: Clinicians will be blinded to most arrhythmia recordings from the LifeVest 
in the group assigned to wear the LifeVest. This is necessary to prevent co-interventions with 
inappropriate anti-arrhythmic drugs or early implantation of an ICD. There are provisions for unblinding 
when clinically indicated, as detailed in Chapter 6 of the Operations Manual. Two types of unblinding 
will occur: 
 
1) Automatic unblinding, generated by the DCC or ZOLL, which will result in electronic notification to 
the site and sending of LifeVest monitoring strips. Automatic unblinding will be initiated if any of the 
following events occurs: 
• 
Participant receives a shock 
• 
LifeVest alarms, but participant averts a shock or the rhythm spontaneously terminates 
if the rhythm lasts > 30 seconds 
• 
Asystole or Bradycardia less than 20 bpm 
2) Clinical sites can request unblinding and receive LifeVest strips under the following circumstances: 
• 
Participant suffers a cardiac arrest, or reports receiving a shock or LifeVest alarm 
• 
Participant complains of syncope or pre-syncope 
• 
Participant complains of palpitations 
• 
Physician deems it to be medically necessary (a protocol deviation may be reported) 
The procedure for requesting these strips will require a case report form (completed by ZOLL personnel) 
with a diagnosis or rationale (as outlined above), the date range of strips requested and a follow-up form 
that documents any treatment changes resulting from viewing these strips. 
 
Crossovers 
Participants randomized to the control arm of VEST should not wear a LifeVest during the 3 month 
VEST follow-up period; use of a LifeVest by a control participant will be recorded as a protocol 
deviation. 
Treatment of Participants Who Receive a LifeVest Shock 
Evaluation and treatment of participants who receive a shock while wearing the LifeVest will be 
determined by the treating physicians. Recommendations for possible evaluation strategies and treatment 
will be included in the Operations Manual (Chapter Guidelines for Care of the Medical Treatment). This 
may include the possibility of assessing for recurrent ischemia, treatment of arrhythmias such as atrial 
fibrillation or titration of medication. 
Early ICD Implantation 
It is recognized that some participants will develop indications for ICD implantation during the 3 
month VEST portion of the study. Given the short follow-up of only 3 months, we anticipate that this 
will be a rare event. The protocol provides for participants in the control (non-LifeVest group) and the 
intervention group (LifeVest group) who suffer an aborted cardiac arrest subsequent to the qualifying 

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MI/hospitalization to be implanted with an ICD. Participants with syncope and >30 seconds of VT may 
also have an ICD implant. 
The following are NOT considered appropriate reasons for early ICD implantation and if elected by 
the treating physician will be considered protocol deviations: 
• 
Malfunction of the LifeVest (Poor sensing or inappropriate detection/shock delivery) 
• 
Poor participant compliance 
• 
Non-sustained ventricular arrhythmias (<30 seconds) 
• 
Asymptomatic ventricular arrhythmias 
In addition, a detailed algorithm for initiation of anti-arrhythmic drugs for ventricular arrhythmias and 
atrial fibrillation based on ACC/AHA Guidelines will be provided in the operations manual.6, 9 
Deviations from these algorithms that are elected by the attending physician will be considered a protocol 
deviation. 
 
1.5.6 
Randomization 
Participants will be randomized in a 2:1 ratio to either receive the LifeVest or not, respectively. Randomization 
will be stratified and blocked to protect against chance maldistribution of important predictors. Stratification will 
be by ejection fraction (<25% vs. >25%) and by revascularization status (i.e., None/PCI/CABG), both known 
strong predictors of mortality, and by clinical site to protect against maldistribution of other unmeasured potential 
confounders that might be unequally distributed at different clinical sites.  Randomization blocks will vary in size 
to protect against predictability of randomization assignment within clinical site/EF/revascularization strata. Block 
size will vary from 3 to 6, allowing for a maximum absolute deviation of 4 participants from the exact 2:1 ratio in 
any given site/EF/revascularization stratum. Separate tables for each stratum will be pre-generated (by existing 
routines developed by the Senior Statistician for the study), encrypted, and accessible only to the Senior Statistician 
and the DCC Data Analyst. 
The DCC will implement a web-based interface that clinical sites will use to obtain randomization assignments 
for each enrolled participant after completion of the Enrollment Visit. Clinical sites will access the randomization 
website using a secure password, and will be prompted to attest that all entrance criteria are met and that informed 
consent has been obtained. Each inclusion and exclusion criterion will require active attestation to minimize errors 
of omission. Once entry criteria are verified electronically, the recruiter will be shown a “randomize” button, and 
will receive the assignment (“Wear LifeVest” or “Do Not Wear LifeVest”) upon activating the button since 
participants and clinical site clinicians are not blinded to treatment assignment. After randomization, the group 
assignment may be printed by the clinical sites from the website along with group-specific study instructions for 
physicians and participants. 
If there is any question regarding eligibility for randomization, the clinical site personnel will contact the CCC 
for adjudication prior to seeking randomization. Every effort will be made to minimize protocol deviations 
regarding participant eligibility for the study, including quality control procedures to assure that the ejection 
fraction (EF) entry criterion is accurate. 
 
1.5.7 
Participant Retention 
We will make every effort to ensure that participants are not lost to follow-up nor drop out of the study. At the 
initial screening and enrollment visit, the clinical site will record identifying information including address, phone 
number, social security number and the name, address and phone number of one family member and two close 
friends able to locate the participant. 
We do not expect many participants to be lost to follow-up given the short 3 month time frame. All the 
participants will be recovering from a recent MI; therefore, they are less likely to travel far or be non-compliant. 
Two thirds of the participants will also be wearing a LifeVest during these 3 months. The LifeVest will be a 
reminder to participants that they are in the study and need to maintain close follow-up with the study coordinators. 
In addition, participants wearing the LifeVest will be required to send data via a modem (integrated into the 
LifeVest monitor) on a weekly basis. This will allow clinical sites to track participants on a weekly basis. The Data 
Management System will identify participants who have missed transmissions and post reports on the study website 
accessed by site coordinators. These will be followed up by e-mail alerts. 

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1.5.8 
Predictor Variables 
The primary predictor variable will simply be randomization to LifeVest or no LifeVest. 
 
1.5.9 
Outcome Variables 
The outcome measures are outlined in Table 3. The primary outcome is sudden death and death due to 
ventricular arrhythmia at 3 months (90 days) after randomization. We will use the following definition of Sudden 
Death: 
 
For witnessed deaths, sudden cardiac death will be defined as an unexpected, non-traumatic, non- 
self-inflicted fatality in otherwise stable participants who die within one hour of the onset of the 
terminal symptoms. For persons dying more than one hour after a cardiac arrest from a 
ventricular arrhythmia, the Non-Sudden Death due to Ventricular Arrhythmia category should be 
used. 
 
For unwitnessed deaths, participants will meet the definition of sudden death if they are found 
dead within 24 hours of being well, assuming there is no evidence of another cause of death 
during that time period. Device arrhythmia and autopsy results may be used when available. For 
unwitnessed deaths when the participant was found dead more than 24 hours after last being 
seen, no device arrhythmia data are available, no autopsy results are available and no other 
information is available regarding the cause of death, the Indeterminate category should be used. 
 
We also include non-sudden deaths due to ventricular arrhythmia in the primary outcome definition. Deaths are 
categorized as such when a person suffers a cardiac arrest from an acute ventricular arrhythmia, is resuscitated and 
admitted to the intensive care unit, and then dies several days after the arrest from complications (e.g., neurological 
damage). Secondary outcomes for VEST are total mortality, non-sudden death and other cause-specific mortality 
(non-sudden fatal MI, other cardiac death, non-cardiac death, and indeterminate cause of death), hospitalization for 
MI, congestive heart failure, stroke/transient ischemic attack, ventricular arrhythmias, adverse events, LifeVest 
compliance, eventual ICD implantation, quality of life, and resource utilization/cost. The wearable defibrillator can 
do continuous ECG recording and monitor time worn. Therefore, data for several of the secondary outcomes that 
are analyzed within the intervention group will come from the LifeVest transmissions. 
 
Outcome Adjudication: The DCC will direct the adjudication of study outcomes. Assigning cause-specific 
mortality, as is required for the primary VEST outcome and a number of important secondary endpoints for VEST, 
can be difficult. Cardiac electrophysiologists actively engaged in clinically relevant patient care will be employed 
to provide expert opinions regarding these endpoints. The Endpoints Director will manage the adjudication process 
designed to categorize arrhythmias and deaths appropriately, minimize bias by blinding adjudicators to treatment 
assignment, and protect against unnecessary disclosure of protected health information. Table 3 lists the primary 
and secondary outcomes, the data source, and whether or not each endpoint requires adjudication. Definitions for 
each endpoint are provided below. 
 
Cause-specific Mortality and Non-Fatal Cardiovascular Events: Deaths will be reported by family members or 
clinicians, or detected by clinical sites when study participants fail to show up for scheduled examinations or miss 
scheduled data transmissions. Social security death index searches will be performed for all participants lost to 
follow-up for whom vital status is unknown in the U.S.. Hospitalizations will be reported by participants at or 
between scheduled examinations or phone calls. Sites will notify the DCC within 48 hours of learning about a 
death or cardiovascular hospitalization, and will then have eight weeks to obtain a death certificate; all discharge 
summaries for any hospitalizations occurring within 1 month of the index death/hospitalization, and narratives from 
personal contacts of deceased participants (listed at recruitment) regarding manner and circumstances of death. All 
personal identifiers and mention of treatment assignment (for the VEST arm) will be carefully stripped by clinical 
site staff to the extent possible. For all deaths, the DCC will redact any mention of the LifeVest in participants 
assigned to VEST, and add fake redaction in participants assigned to NO VEST so that adjudication of cause of 
death will be blinded. ECG data from the LifeVest will NOT be used to adjudicate fatal outcomes for VEST, 

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because this information will not be available on participants without a LifeVest, and use might induce bias from 
differential measurement error. Complete packets will be assembled by the DCC and read independently by two 
adjudicators. Every death will be categorized according to the cause-specific mortality and non-fatal cardiovascular 
event categories described in Table 3. Disagreements will be resolved by consensus, involving a third adjudicator 
when required. 
 
Ventricular Arrhythmias: Electronic rhythm strips recorded by the LifeVest will be uploaded to the study database 
via electronic data transfer from ZOLL. Strips will be presented to adjudicators in batches, with study ID numbers 
and adjudication forms and read independently by two cardiac electrophysiologists. Adjudicators will determine 
whether the LifeVest therapy was “appropriate” or “inappropriate” based primarily on the presence or absence of a 
true ventricular arrhythmia. Discordances will be resolved by consensus, involving a third adjudicator when 
required. 
 
Quality of Life: Quality of life outcomes will be measured using self-administered questionnaires mailed to 
participants 1-2 weeks prior to the 3 month visit. QOL will be assessed using the SF-36 for health related quality of 
life, the CES-D to measure depression, the Spielberger STAI to measure anxiety, and the MOS sleep scale to 
measure sleep patterns. The EQ-5D will be administered to measure subjective health status, and the International 
Physical Activity Questionnaire (IPAQ) short format for physical activity. The Florida Patient Acceptance Scale 
(FPAS) will be included to measure device acceptance in those randomized to the LifeVest. 
 
Economic Outcomes: Cardiovascular hospitalizations, visits to emergency rooms, unscheduled cardiovascular 
outpatient visits and adverse events will be collected at the follow-up visits by self-report, including the reasons for 
admission and length of stay. All admissions will be assigned to a DRG based on participant report and review of 
medical records obtained to document clinical outcomes. The number of physician visits, major tests, and 
medications will be collected using a brief survey. For VEST, we will compare costs over follow-up between 
participants assigned to the LifeVest and those assigned to usual care. We will analyze whether the costs of 
management, apart from the cost of the LifeVest itself, are lower in the vest assigned participants. This approach 
will allow us to determine if there are any cost savings in the VEST arm participants that will offset the expected, 
planned costs of the intervention. In a secondary analysis, we will compare total cost (i.e., costs including the cost 
of the LifeVest) between the two randomized groups, and calculate confidence limits on the cost difference 
between the two groups using a bootstrap resampling approach. 
 
 
1.5.10 Adverse/Outcome Events 
Most symptoms, signs and clinical events will be captured by questionnaire during routine scheduled clinic and 
telephone visits.  Data collection forms are specifically designed to capture known adverse events from the 
LifeVest including physical discomfort (rash, etc.). Inappropriate shock events will be adjudicated, as above. Site 
investigators will make a determination for all deaths and hospitalizations about whether the event was related to 
participation in the study; all such events will be adjudicated and summarized for the Data Safety Monitoring Board 
(DSMB). 
 
 
1.5.11 Analysis Plan for VEST 
Treatment effects on the primary outcome, sudden death and death due to ventricular arrhythmia, will be 
assessed using stratified exact methods to compare cumulative incidence in the VEST and control groups at 60/90 
days. An exact test of the primary null hypothesis of no treatment effect will be conducted using a two-sided alpha 
of 5%. This analysis will be by intention to treat (ITT), without regard to adherence to the assigned study 
intervention or other aspects of care. The analysis will be jointly 
 
Table 3. Outcome measures for VEST. 
OUTCOMES 
PRIMARY/S 
ECONDARY 
DATA SOURCE 
ADJUDICATED 
Sudden death mortality 
Primary 
Records/interviews† 
Yes 
All-cause (total) mortality 
Secondary 
Records/interviews† 
Yes 

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Cause-specific mortality 
Non-sudden death 
Secondary 
Records/interviews† 
Yes 
Ventricular Arrhythmia Death 
Primary 
Records/interviews† 
Yes 
Other Fatal Arrhythmia 
Secondary 
Records/interviews† 
Non-Sudden Fatal MI 
Secondary 
Records/interviews† 
Yes 
Fatal Congestive Heart Failure 
Secondary 
Records/interviews† 
Yes 
Other Cardiac Death 
Secondary 
Records/interviews† 
Yes 
Fatal Stroke 
Secondary 
Records/interviews† 
Yes 
Other Non-cardiac Death 
Secondary 
Records/interviews† 
Yes 
Indeterminate Cause of Death 
Secondary 
Records/interviews† 
Yes 
Time to death after 1st VT/VF episode 
Secondary 
Records/ICD/Reveal 
Yes 
Non-Fatal Cardiovascular Events 
MI 
Secondary 
Records/interviews† 
Yes 
Atrial fibrillation 
Secondary 
Records/interviews†/ 
ICD/Reveal 
Yes 
Congestive heart failure 
Secondary 
Records/interviews† 
Yes 
Stroke 
Secondary 
Records/interviews† 
Yes 
LifeVest Events 
Ventricular Tachyarrhythmia 
Secondary 
LifeVest 
Yes 
LifeVest Shocks delivered 
Secondary 
LifeVest 
Yes 
30 Beats of VT (CL 330-370 msec) 
Secondary 
LifeVest 
Yes 
Inappropriate Shock - SVT 
Secondary 
LifeVest 
Yes 
Inappropriate Shock - Malfunction 
Secondary 
LifeVest 
Yes 
Time to 1st episode of VT/VF 
Secondary 
LifeVest 
Yes 
Adverse Events 
Device-attributable Death or Hospitalization 
Secondary 
Records/interviews† 
Yes 
Device-related Symptom or Sign 
Secondary 
Data Form 
No 
Device Change-out 
NA 
Data Form 
No 
Other Adverse Event 
Secondary 
Data Form 
No 
Vest Compliance 
Secondary 
LifeVest 
ICD Implantation 
Secondary 
Data Form 
No 
Quality of Life 
Secondary 
QOL Instruments 
No 
Resource Utilization/Cost 
Secondary 
Data form 
No 
 
† - Includes information from medical records, death certificates, interviews of next-of-kin or personal physicians, and National Death Index 
searches 
VF – Ventricular fibrillation; VT – Ventricular tachycardia; SVT – Supraventricular tachycardia; ICD – Implantable cardioverter defibrillator 
 
stratified by length of follow-up period (to account for the higher expected rate in patients with 90 day follow-up), 
and randomization stratum, as jointly defined by EF and receipt of PCI and/or CABG during the hospitalization for 
the index MI. 
We will also conduct a secondary “modified intention-to-treat” analysis of sudden death and death due to 
ventricular arrhythmia, total mortality, and other secondary outcomes. For this analysis, follow-up time will start at 
the time of discharge instead of randomization, and end 60/90 days after discharge, and participants who are 
randomized but die before discharge from the index hospitalization will be excluded. For death outcomes, this 
analysis will use the stratified exact methods specified for the primary analysis; for more common secondary 
outcomes, asymptotic methods will be considered. 
We will also analyze treatment effects on overall mortality and non-sudden death, non-fatal cardiovascular 
events, ventricular arrhythmias, adverse events, LifeVest compliance, ICD implantation, quality of life and resource 
utilization/cost. For rare outcomes, exact methods will be used, as for the primary endpoint. For VEST therapies 
and hospitalizations, we will use the Anderson-Gill extension of the Cox model for repeated events, with robust 
standard errors, to better capture information from high-risk participants with repeated VEST therapies or 
hospitalizations. 
We will also conduct a secondary, “as treated” analysis of sudden death and death due to ventricular 
arrhythmia, total mortality, and other secondary outcomes. The primary ITT analysis will estimate effectiveness of 
the vest, averaged over variations in compliance. We will attempt to estimate the efficacy of the vest for prevention 
of sudden death and death due to ventricular arrhythmia as well as total mortality using survival models treating 
observed vest use as a time-dependent covariate. For sudden death and death due to ventricular arrhythmia, we will 

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use a Fine-Gray model treating other deaths as competing risks; a standard Cox model will be used for total 
mortality. 
 
1.5.12 Sample Size Calculations 
When the trial was originally designed, the sample size for the VEST study was estimated to be 1,890. This 
assumed a power of 80%, with a 2-sided alpha of 0.05 and a 2:1 randomization scheme. The VEST sample size was 
carefully computed using data-based estimates of the following factors: 
 
1. Mortality due to sudden death in the first 2 months following an MI in patients with EF≤35% is 2.4%.The 
VALIANT Study, the EPHESUS Study, and the DINAMIT Study are three recent studies reporting on 
mortality and sudden death rates in the early period following an MI in populations similar to our study 
population. A meta-analysis of these three studies populations gives a summary estimate for sudden death 
rate of 2.4%. 
 
2. Mortality due to sudden death in the first 3 months following an MI in patients with EF≤35% is 3.0%. 
Using month-by-month data on sudden death in VALIANT, we estimate that extending follow-up from 2 to 3 
months will increase the sudden death rate by 25%, from 2.4% to 3.0%. This accounts for declines in the 
sudden death rate in the weeks following MI. 
 
3. Mortality due to ventricular arrhythmias in the first 3 months following an MI in patients with EF≤35% is 
2.73%.The wearable defibrillator vest will be effective at reducing only sudden death due to a ventricular 
arrhythmia. The preliminary data from the wearable defibrillation vest shows that 91% of all sudden cardiac 
arrests are due to ventricular arrhythmias. This is consistent with estimates in the literature. Therefore, 91% 
of 3.0% would give us an expected mortality of 2.73% due to ventricular arrhythmia. 
 
4. The effectiveness of the wearable defibrillator to reduce sudden death due to ventricular arrhythmias will 
be 71.9%. Previous analyses show that the LifeVest conversion success rate is 98% for syncopal VT/VF. 
Based on early experience in VEST and planned changes in randomization procedures, we have targeted an 
intention-to-treat compliance rate with the LifeVest of 70%. This means that participants assigned to the 
LifeVest will wear it for 70% of all hours in the 3 months following randomization, including days when the 
LifeVest is not worn at all. However, since compliance and event rates are both anticipated to be highest in 
the earliest weeks of the trial we anticipate the LifeVest will be used during more than 70% of sudden death 
events. Thus, we estimate that the LifeVest will reduce sudden death due to syncopal VT/VF by 71.9%. 
 
5. Given the above assumptions, we estimate an overall sudden death rate of 3.0% in the control group and 
1.02% in the wearable defibrillator group (67% reduction in sudden death). The absolute reduction in 
mortality is the mortality from ventricular arrhythmia (2.73%) times the effectiveness of the LifeVest 
(71.9%) = 1.98%. Thus, the sudden death rate in the defibrillator LifeVest group is expected to be the 
mortality in the control group minus the absolute reduction or 3.00%-1.98% = 1.02%. 
 
6. Given the short follow-up period (3 months) and strong efforts to collect complete data, we anticipate 
minimal loss to follow-up and minimal crossover. Crossover in the treatment group (LifeVest group) is 
accounted for in #4 above (some patients will not tolerate the LifeVest). Given that the LifeVest is only 
available by prescription, we expect that crossover from the control group to the treatment group will be 
exceedingly rare. 
 
7. A power of 80%, with a 2-sided alpha of 0.05 and a 2:1 randomization scheme. Using these estimated 
event rates, a 2:1 randomization scheme and the standard formula for two-group comparisons of proportions, 
we will need a sample of 1260 in the wearable defibrillator group and 630 in the control group, or 1890 total 
participants. 
 
Updating the Sample Size for VEST: We recognized that this sample size calculation is sensitive to the values of 
the inputs noted above. This raises the concern that the VEST trial might fail to reach firm conclusions despite the 

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anticipated efficacy. Rates of total mortality, sudden death and death due to ventricular arrhythmia, and LifeVest 
compliance are especially important drivers of sample size, and these are easily monitored during follow-up. We 
therefore plan to update our sample size after 1000 participants have completed their VEST follow-up and then 
again after 1500 participants have completed follow-up. We will use interim overall rates of total mortality and 
sudden death and death due to ventricular arrhythmia, as well as LifeVest compliance and crossover rates (off- 
protocol use of the LifeVest in the NO VEST arm), in conjunction with our original assumptions about the 
proportion of all sudden deaths that are due to ventricular arrhythmias and the efficacy of the LifeVest  in 
preventing these potential events. We will also account for time in the hospital after randomization but before 
discharge (using real estimates of time-to-discharge from the study), during which the LifeVest is typically not 
worn and when we expect no differential effect on mortality to be induced by assignment to VEST. Because this 
procedure is blinded to treatment assignment, no meaningful inflation of the type-I error rate is expected.11, 12 
The following limits will be adhered to when updating the sample size: 
• The sample size will be updated only if the revised sample size is more than 10% larger than the planned 
value of 1900, i.e., greater than 2100. 
• The updated sample size will not exceed 4,000 (twice the current planned sample size). 
• No decrease in the planned sample size will be allowed (outside of the direction of the DSMB). 
 
FINAL SAMPLE SIZE: In October 2015, after 1500 participants completed follow-up, the VEST Data and Safety 
Monitoring Board (DSMB) reviewed the blinded sample size re-estimation calculations and was concerned that 
with the estimated power at the current sample size (n=1890) there is a substantial likelihood of type II error. 
Therefore, the DSMB recommended that the VEST sample size be increased in order to achieve an estimated 
power of at least 70%, with a composite sudden death rate in the trial of 1.66%. 
 
On April 25, 2016, the VEST Steering Committee approved the increase in sample size to a total of 2300 
participants. 
 
1.6 DATA REPOSITORY 
All primary data (including that collected via questionnaire, testing, LifeVest interrogation) will be stored in a 
study-wide database. 
 
1.7 VEST REGISTRY 
In order to determine long-term outcomes in patients who are eligible and enroll to participate in VEST, all 
patients in the VEST Registry will have at least yearly follow-up to determine vital status, most recent EF, whether 
an ICD has been implanted and whether they have had any cardiovascular hospitalizations/events. These will be 
obtained by searching medical records and death indexes, and by interviewing participants by phone. 
 
1.7.1 
U.S. National Death Index Search at End of the Trial 
 
At the end of the trial, we will perform a National Death Index search for U.S. participants with unknown vital 
status to obtain data on the primary (sudden death) and secondary (all cause mortality) study outcomes. 
Confirmation of VEST participant deaths is of vital importance, in order to reduce the risk of missing data bias 
which may impact the robustness of the final trial results. The International Conference on Harmonization (ICH) 
guidelines on Statistical Principles for Clinical Trials14, which has been adopted by the U.S. FDA, state “Missing 
values represent a potential source of bias in a clinical trial. Hence, every effort should be undertaken to fulfill all 
the requirements of the protocol concerning the collection and management of data.” 
 
The proposed NDI search qualifies for a waiver of consent. Federal regulation 45 CFR 46.116(d) establishes four 
criteria for waiving consent or altering the elements of consent in minimal risk studies. 
 
1. The research involves no more than minimal risk; 

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• 
The NDI search involves no more than minimal risk, since the only potential risk of the NDI search is a 
possible loss of confidentiality for VEST participants that have unknown vital status at the end of the 
study period. Based on the current rate of unknown vital status in VEST to date (as of June 2016), it is 
estimated that only 6% of all randomized participants (6% of 2300 = 138 participants) will have 
unknown vital status at the end of the trial. The UCSF Data Coordinating Center will do the 
following to minimize the risk of a loss of confidentiality: (1) access to NDI search data that 
includes possible identifiers will be limited to the unblinded statistician and the unblinded 
DSMB project director; (2) NDI search data with identifiers will be temporarily stored on a 
restricted access server that is encrypted and password protected. This is necessary for the 
data to be reviewed for accuracy during the matching process; (3) After completion of the 
matching process and vital status for the approx. n=138 participants has been determined, all 
electronic (and hardcopy data, if any) NDI data containing identifiers will be destroyed. 
 
2. The waiver or alteration will not adversely affect the rights and welfare of the subjects; 
• 
The NDI search will not adversely affect the rights and welfare of the VEST participants, since the only 
potential risk of the NDI search is a possible loss of confidentiality for VEST participants that have 
unknown vital status (approx.. n=138). 
 
3. The research could not practicably be carried out without the waiver or alteration; and 
• 
There is no other option for obtaining the data necessary to answer this trial’s key research objective 
regarding the primary study outcome (death) without the NDI search for the participants with unknown 
vital status at the end of the study period. Prior to classifying a participant as having “unknown vital 
status”, the clinical sites will attempt to obtain vital status using all available options, as possible (e.g., 
contacting the participant using all available contact information (i.e., U.S. mail, email, phone), 
contacting family/friends, search of available medical records, search of public records, including 
obituaries and genealogy websites). Only after these options have been exhausted will the participant 
be included in the list of individuals to be submitted to the NDI. It would not be possible to obtain 
consent to do the NDI search for these participants with “unknown vital status” at the end of the trial. 
 
4. Whenever appropriate, the subjects will be provided with additional pertinent information after 
participation. 
• 
The NDI search will only provide results for the potential confirmation of death outcomes in VEST 
participants. Therefore, this criteria does not apply. 

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PART 2. COORDINATING CENTERS’ PLAN 
 
2.1 ORGANIZATION AND ADMINISTRATION 
The study-wide organization chart is shown in Figure 1-2. 
 
2.1.1 
Coordinating Centers 
There are two separate and 
independent coordinating centers for 
VEST. A Clinical Coordinating Center 
(CCC), led by Jeffrey Olgin, MD, 
responsible for day-to-day operations of 
the study as it relates to participant 
enrollment and clinical site 
administration, and a Data Coordinating 
Center (DCC), led by Mark Pletcher, 
MD, MPH responsible for assuring 
excellence of all aspects of data 
acquisition and analysis for the study. 
The PIs and staff of the coordinating 
centers will work cooperatively to assure 
the successful achievement of the studies’ 
specific aims. One of the reasons for 
separate coordinating centers is to assure 
that the PI and staff members of the CCC 
do not have access to the study database, 
 
Figure 1-2 Study-wide organization and governance. 
 
which resides with the DCC, and remain blinded to study outcomes until all participants have completed the 
clinical trial. 
The CCC manages the clinical sites, which includes overseeing the quality of clinical measurements obtained in 
the study and ensures adherence to the study protocol. The CCC is responsible for all aspects of participant 
recruitment. This includes development of the operations manual, training activities, getting sites up and running, 
facilitating recruitment strategies and monitoring recruitment progress. The CCC will adjudicate decisions 
regarding participant eligibility. The CCC is also responsible for managing and oversight of clinical site 
monitoring. Finally, the CCC is responsible for preparing the agenda and materials for Steering Committee 
meetings. 
The primary functions of the DCC include creation of tamper-proof systems for randomization and analysis of 
blinded data analysis, development of the data forms, training and certification of clinical site staff in the data 
management system, randomization of participants for the intervention phase of the study, acquisition of data from 
the clinical sites and monitoring devices, data quality control, event adjudication, and data analysis. The DCC is 
also responsible for coordinating and supporting the activities of the DSMB. 
 
2.1.2 
Committees and Governance 
Steering Committee. The Steering Committee will be responsible for general scientific oversight and progress 
of the study. The Steering Committee will be responsible for overseeing study progress including ancillary studies, 
and for scientific policies, integrity and direction. It will appoint the analysis and publications committee and 
writing groups, ensuring that information from the study is disseminated in the scientific literature and at scientific 
meetings. The committee will be chaired by Dr. Olgin and will be comprised of the CC co-investigators (Drs. 
Pletcher and Lee), statistician (Dr. Vittinghoff), representatives from ZOLL, select consultants and site PIs. 
Industry representatives will be non-voting members on the committee. A list of Steering Committee Members is 
attached. The Steering Committee will meet at least twice in the 1st year and then at least once yearly in person, 
videoconference or teleconference. 
 
Executive Committee. An executive subgroup of the Steering Committee will be responsible for decisions that 
require attention between Steering Committee meetings, and for major financial, administrative, and operational 

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decisions. The Executive Committee will consist of Dr. Olgin (chair), Dr. Lee, Dr. Pletcher, Dr. Vittinghoff, and 
one representative from ZOLL. Industry representatives will be non-voting members on the committee. 
 
Quality Control (QC) Committee. The QC Committee will be responsible for assuring that the methods and 
procedures of the study are carried out uniformly and with a high level of quality. It will be co-chaired by Dr. 
Pletcher (DCC) and Dr. Lee (CCC), with Dr. Pletcher leading the portion of the meeting devoted to data quality, 
and Dr. Lee leading the portion devoted to clinical procedures. Members of the committee will include the project 
directors of the DCC and CCC, representatives from all clinical sites (study coordinators), and ad hoc participation 
by representatives from ZOLL and study-wide consultants when needed. 
 
Data Safety Monitoring Board (DSMB).An independent DSMB will be responsible for reviewing the outcome 
data obtained at regular intervals to recommend decisions designed to assure the safety of the participants, the 
integrity of the scientific effort, and the optimal timing for ending VEST recruitment. 
 
2.2 OPERATIONS MANUAL, FORMS 
In consultation with the Steering Committee and Investigators in the CCC, the DCC will design and produce 
the data collection forms for the study during the planning phase. The DCC and CCC will jointly develop a 
comprehensive Operations Manual, updating it as needed with careful version control. The Operations Manual will 
serve as a guide for training clinical site personnel, as well as for standardizing procedures for data acquisition and 
editing during the study. 
 
2.3 DATA MANAGEMENT SYSTEM 
The DCC has a customized hybrid of off-the-shelf software combining decentralized data submission, 
centralized and remote data editing, and a centralized database structure designed to collect, transfer and store data. 
In this system, data are collected on Teleform forms and transmitted electronically (via fax) to the DCC by remote 
clinical sites. Electronic data are received at the DCC and assessed by both automated and manual processes before 
being entered into the study-wide database. Every 24 hours, data discrepancies (queries) are automatically 
generated identifying potential errors in the data. Clinical site staff members access their own data queries via the 
secure web site and resolve them in a timely manner. An audit trail of changes to the data is automatically 
produced. Data from outside sources, such as central reading centers or core laboratories, is integrated into the 
study-wide database. 
 
Study-wide Communications/Website: Most communication and problem-solving regarding data management 
issues will occur through a central website provided by our data management system. The private, secure website 
provides access to a study-wide directory with phone numbers, fax numbers and e-mail addresses of all clinical 
sites and core labs. It serves as a central repository for study documents including the operations manual, meeting 
and conference call minutes, all-site emails, and all required data forms, which can be directly downloaded from the 
website. 
 
Data Collection and Editing at the Clinical sites: Our data system uses machine readable forms and Internet 
technology to provide rapid and timely access to accurate and high quality data. The clinical sites complete the 
machine-readable data forms and transmit them to the DCC using standard fax machines. All that is required at the 
participating sites is a fax machine and a high-speed Internet connection. When the data arrives at the DCC, the 
data forms are received as an electronic image and are automatically evaluated using Teleform software. As each 
form is verified by a DCC staff member, the data is automatically written to the study’s Microsoft SQL Server 
database. 
Each hour, all of the study data is subjected to error-checking programs that check for completeness, 
consistency and validity. The results of the error-checking procedures are posted to the study web site where 
clinical site personnel check it daily to both confirm that the DCC has successfully received all of the faxed forms 
and to address the errors that have been detected. In all such procedures, site personnel will have access only to 
their own site’s data. 

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Data Transmission from Reading Centers, Laboratories: For data that is electronic in nature, such as from the 
LifeVest, the DCC will establish a system for efficient transfer of this data directly to the DCC database andwill 
monitor it for completeness and quality. 
 
 
2.4 COMPUTER AND DATA SECURITY 
The DCC follows standard operating procedures (SOPs) for computer system security to ensure the 
confidentiality and validity of study data. The SOPs are designed to prevent unauthorized access and limit 
authorized access to our computer systems and are in compliance with established standards for Information 
Technology Security. Our network is privately maintained, hardware fire-walled and none of the workstations or 
database servers can be directly addressed from outside the Local Area Network. Study website and database access 
requires a network domain account with appropriate account-specific permission on the database. All requests for 
new accounts and access to the database must be documented by a System Access Request Form signed by the 
project director. 
All study data will be stored on SQL servers at the DCC at 185 Berry St., San Francisco. Each server is 
backed-up nightly to disk and mirrored to a “failover” site at our co-location facility at 650 Townsend St., San 
Francisco. These two sites have copies of the study database and all associated systems required to carry on the 
study in the event of a disaster in one of the locations. In addition, backup copies of the entire enterprise 
(databases, user workstations, file servers, etc) are archived in Sacramento, California by Recall, Inc. This will 
protect the study data in case of a natural disaster affecting the San Francisco Bay Area. All servers are housed in 
a new (2005) state-of the-art secure server room. Access to the server room is via a limited access suite occupied 
by our Information Technology (IT) staff. Both the suite and server room doors are fitted with an Access Control 
System. Only critical IT staff members are allowed to enter the room. All others who enter the server room (e.g., 
air conditioning repairman) must be accompanied by a member of the IT staff and their visit is logged. 
Website communications are encrypted at the 128-bit level using an SSL certificate issued by Verisign 
(Verisign, Inc, Mountain View, CA). All servers are protected from viruses by Network Associates Netshield 4.x, 
Groupshield, and VirusScan Enterprise 7.x (McAfee, Santa Clara, CA). This software automatically checks for 
virus signature file updates from Network Associates’ FTP and HTTP sites once an hour. All anti-virus software is 
monitored and IT personnel are notified in the event that the software stops functioning on a particular server. 
 
2.5 TRAINING, SITE VISITS AND QUALITY CONTROL 
Central Training Session: A central training session for clinical site personnel will be held prior to 
the start of participant enrollment in the study. All staff will be trained on use of the LifeVest, study 
protocols, and the data system. At the initial training session, the clinical site coordinators will receive the 
Operations Manual, which will serve as a guide to the training session. The subsequent expectation is that 
if a trained staff member leaves during the study, he or she would train his/her replacement. Since that is 
not always possible, we have found that new staff members are fairly readily able to learn the procedures 
of the study and the data system by reading the Operations Manual, either a site visit to a nearby site or 
from the CCC, and frequent telephone and email contact with the CCC and DCC. 
 
Site Visits to Clinical Sites: Every clinic will be site visited soon after starting recruitment by a 
representative of the CCC, DCC or industry partner, and a structured review of facilities and equipment, 
procedures, files, systems and data will be carried out. In addition there may be early visits by 
representatives of ZOLL to help maximize LifeVest adherence as discussed above. Subsequent site visits 
will be scheduled as needed, and to address quality control issues that come to light in the clinical and 
data monitoring procedures described below. In addition, routine site monitoring by CCC, DCC or ZOLL 
will occur throughout the study duration and at close-out. 
 
Data Quality Control and Verification at the DCC: The distributed nature of the data system 
emphasizes error identification and resolution at the clinical site soon after entry via the data query system 
described above. The primary advantage of this system is to concentrate data editing closer to the data 
collection process, which will result in the following benefits: (1) site personnel will have better 

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recollection of the data making resolution easier and more efficient, (2) data errors will not build up over 
time and remain manageable, (3) early recognition of errors by site personnel can prevent them from 
making the same errors again, and (4) data will be cleaner for interim reports and presentations to the 
DSMB. Once the data arrive at the DCC, there is a multi-step approach for data verification and quality 
control, including: 
• 
100% visual verification of all data values as interpreted by Teleform Reader optical 
character recognition (OCR) against scanned images of the completed source data collection 
forms 
• 
Data form specific insertion criteria (via SQL triggers) to prevent duplicate or incorrectly 
identified form entry 
• 
Missing forms reports based on temporal or logical relationships, generated by a batch 
Visual Basic application. These reports will be made available on the study web site. 
• 
Comprehensive univariate and multivariate field discrepancy identification by a Visual 
Basic query generation application. These queries will involve within-form and cross-form 
comparisons and will appear on the study web site for real-time resolution by the clinical 
sites. 
• 
Complex and resource-intensive second-tier data cleaning in SAS. 
 
The data management system provides an audit trail that tracks what variables have been changed, the 
date they were changed, and which staff member made the changes. In addition, site PIs or Co-PIs will be 
required to review and approve each participant dataset to ensure data integrity. 
 
Data Monitoring: The DCC will design reports that will be accessible to all sites from the study 
website. Most reports will display data stratified by clinical site, introducing a healthy competition 
between centers.  Examples of such monitoring reports include: recruitment reports comparing goal 
versus actual recruitment rates by center; visit compliance reports comparing the number of expected 
visits to actual visits for each protocol-required visit; participant retention reports indicating the number of 
participants active, completed, lost, etc; missing forms reports; missing data reports (for specific critical 
data fields or variables), etc. These reports will be reviewed every month on Quality Control Committee 
conference calls and periodically brought to the attention of the Steering Committee. These types of 
monitoring reports will also be presented to the DSMB along with outcomes data.  Such reports are 
critical to identify study-wide problems as well as problems specific to particular clinical sites, and since 
the reports are available “real-time”, problems can be addressed before they become entrenched. 
 
2.6 STATISTICAL ANALYSIS AND DISSEMINATION 
The DCC will be primarily responsible for statistical analysis of the research questions posed by 
VEST. The data will reside with the DCC and will be analyzed by DCC personnel for interim DSMB 
reports and for publications, presentations and other dissemination activities according to the plan 
described in section 1.5.11 and with scientific oversight by the Steering Committee. 
 
2.7 CLOSE OUT 
During the final 6 months of the study, data quality control checks will be completed and a final 
version of the database files created. In cooperation with the Steering Committee, DCC and CCC staff 
will participate in preparation of the main report and other analyses and writing tasks. The DCC and CCC 
will coordinate the analysis, presentation and publication of study findings upon study completion. The 
Steering Committee will act as a Publications Subcommittee charged with developing a list of publication 
topics together with authorship lists. 

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A set of study documents (protocol, forms, questionnaires and operations manual) will be archived. 
Database files, as well as statistical analysis files, will be documented and archived. 

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Appendix 1.A Abbreviations 
 
 
ACC 
American College of Cardiology 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AHA 
American Heart Association 
CABG 
Coronary Artery Bypass Grafting surgery 
CCC 
Clinical Coordinating Center 
CCU 
Coronary Care Unit 
CHF 
Congestive Heart Failure 
CMS 
Centers for Medicare Services 
CRF 
Case Report/Record Form 
CRT 
Cardiac Resynchronization Therapy 
DCC 
Data Coordinating Center 
DI 
Detection Interval 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
EF 
Ejection Fraction 
FVT 
Fast VT 
HRV 
Heart Rate Variability 
ICD 
Implantable Cardioverter Defibrillator 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
MI 
Myocardial Infarction 
MVP 
Minimal Ventricular Pacing 
NIH 
National Institutes of Health 
NHLBI 
National Heart, Lung and Blood Institute 
NID 
Number of Intervals to Detect 
NIPS 
Non-invasive Programmed Stimulation 
NSVT 
Non Sustained Ventricular Tachycardia 
QOL 
Quality of Life 
RNID 
Number of Intervals to Redetect 
PCI 
Percutaneous Coronary Intervention 
SVT 
Supraventricular Tachycardia 
VF 
Ventricular Fibrillation 
VT 
Ventricular Tachycardia 

VEST 
Statistical Analysis Plan 
Version 1.0 to Version 1.1 (5/12/2012) 
1. Primary endpoint revised from sudden cardiac death to sudden cardiac death or non- 
sudden death to ventricular arrhythmia (Section A, page 1). 
Version 1.1 to Version 1.2 (12/5/2016) 
1. Analysis of primary endpoint revised to use a simple chi-square test rather than exact 
stratified methods (Section A, page 1). 
2. Section on Exploratory Analysis of Compliance added (Section B.4, page 2). 
 
Version 1.2 to Version 1.3 (3/2/2017) 
1. Plan is added for weighted sensitivity analysis of primary outcome omitting patients with 
indeterminate cause of death or unknown vital status (Section B.1.3) 

Version 1.3, 02Mar2017_DSMB approved 
1 
 
VEST 
Statistical Analysis Plan 
 
A. Primary Analysis 
 
Treatment effects on the primary outcome, sudden death or non-sudden death due to ventricular 
arrhythmia, will be assessed using a chi-square test to compare incidence proportions in the 
VEST and control groups at 60/90 days after randomization. The test of the primary null 
hypothesis of no treatment effect will be conducted using a two-sided alpha of 5%. This analysis 
will be by intention to treat (ITT), according to treatment assignment, without regard to adherence 
to the assigned study intervention or other aspects of care. 
 
B. Secondary Analyses 
 
B.1. Sensitivity Analyses 
Results will be checked for robustness in three planned sensitivity analyses. 
 
1. Modified intention to treat. We will omit from this analysis, patients who do not survive until 
discharge from the index hospitalization, and the 60/90 day follow-up will begin at the later event 
of randomization or discharge. The rationale is that the vest is essentially never worn in hospital, 
and so can provide no protection until after discharge. Although mortality is highest soon after a 
serious MI, close in-hospital monitoring is expected to keep the in- hospital death rate low. As 
part of this analysis, we will characterize times from randomization to discharge using histograms, 
stratified by group. 
 
2. Adjustment for baseline imbalances. If we find substantial imbalances in powerful baseline 
prognostic variables with the potential to confound treatment assignment meaningfully, we will 
perform a sensitivity analysis using a logistic regression model to adjust for these factors. If more 
than two factors need to be adjusted for, we will summarize them using propensity scores 
[Rosenbaum 1983], then use a logistic model to adjust for the scores as a three-knot cubic spline, 
requiring two basis functions, so that the conservative rule of thumb of approximately 10 events 
per variable is observed [Vittinghoff 2006]. 
 
3. Inverse weighting to deal with indeterminate cause of death and missing vital status. In the 
primary analysis, participants with indeterminate cause of death or missing vital status will be 
assumed not to have had a primary study event. In two secondary analyses, we will restrict the 
analysis to deceased participants with determinate cause of death and those known to be alive, 
weighting these observations so that their baseline correlates of the primary outcome are 
representative of the entire randomized cohort. To do this, we will develop two logistic models: 
the first for having determinate cause of death among all patients known to have died, and the 
second for having known vital status among all participants. Weights will be calculated as the 
inverse of the product of the fitted probabilities from these two models, after assigning a fitted 
probability of 1 from the first model for patients known to be alive. Variables in each model will be 
selected, without regard to the primary outcome, from a list of known correlates of the primary 
study outcome, as specified by Drs. Olgin, Lee, and Pletcher. To deal with missing values of the 
candidate variables in the a priori list, multiple imputation will be used, followed by averaging of 
the weights obtained from each of ten completed datasets. Two versions of this sensitivity 
analysis will be conducted, the first excluding and the second using information from the vest in 

Version 1.3, 02Mar2017_DSMB approved 
2 
 
determining vital status. The weighted analyses will use procedures properly accounting for the 
slightly smaller sample size available for analysis. 
 
B.2. Heterogeneity of treatment effects 
o By randomization stratum. We will use a logistic model to assess heterogeneity of the 
treatment effect across the 6 randomization strata jointly defined by EF, PCI, and CABG, as well 
as across the 2 strata defined by EF and the 3 strata defined by PCI and CABG. Nominal 
differences across strata will be conservatively interpreted in the light of tests for interaction 
between treatment and stratum, using a Bonferroni-corrected two-sided alpha of 0.05/3=0.0167. 
In additional exploratory analysis, we will assess modification of the ITT treatment effect by drugs, 
NYHA class, BMI, gender, and compliance 
 
B.3. Treatment effects on secondary endpoints 
o Total mortality, revascularization, ICD implantation. Treatment effects on these binary 
secondary endpoints will be analyzed using chi-square tests, as proposed for the primary 
analysis. Logistic regression will be used to adjust for baseline imbalances as needed. 
 
o Re-infarctions and hospitalizations.Treatment effects on these potentially recurring outcomes 
will be analyzed using the Anderson-Gill extension of the Cox model for recurrent events, with 
robust standard errors [Therneau 2000], to account for potential clustering of recurrent outcomes 
within participants. 
o Vest-related symptoms. Fisher’s exact tests will be used to compare frequency of potentially 
vest-related symptoms currently tabulated in the DSMB report, including fatigue, back pain, 
trouble sleeping, and upper body rash and itching. 
 
B.4. Exploratory analysis of compliance 
Factors associated with compliance with the VEST will be examined in an exploratory, 
hypothesis- generating analysis focusing on seasonality, site, geographic region, body mass 
index (BMI), time on study, baseline EF, as well as age, gender, race/ethnicity, education, marital 
and employment status, NYHA Class, and length of hospital stay. The analysis will use two-part 
models for repeated daily compliance measures, the first a GEE logistic model for any use of the 
VEST, and the second a GEE linear model for hours of use, transformed as necessary to meet 
normality assumptions, for patient-days where any use is detected. Inference for the combined 
effects of each proposed covariate on both elements of compliance (any use and hours of use 
among users) will be implemented using the seemingly unrelated estimation strategy. [Weesie, 
1999] 
 
C. References 
• 
Rosenbaum P, Rubin D. The central role of the propensity score in observational studies 
for causal effects Biometrika. 1983;70:41-50. 
• 
Therneau T, Grambsch P. Modeling survival data: extending the Cox model. New York: 
Springer; 2000. 
• 
Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and 
Cox regression. Am J Epidemiol. 2006:165(6):710-8. 
• 
Weesie, J. 1999. sg121: Seemingly unrelated estimation and the cluster-adjusted 
sandwich estimator. Stata Technical Bulletin 52: 34–47. Reprinted in Stata Technical 
Bulletin Reprints, vol. 9, pp. 231–248. College Station, TX: Stata Press.