Strategic MAnagement to Optimize Response To Cardiac Resynchronization Therapy Registry (SMART Registry)
Conditions: Heart Failure
Sponsor: Boston Scientific Corporation

 
 
 
 
Protocol & Statistical Analysis Plan  
Cover Page 
 
 
 
SMART Registry 
Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
 
 
 
CLINICAL INVESTIGATION PLAN 
ver. B, dated 06 Feb 2017  
 
 
 
ClinicalTrials.gov Registration: NCT03075215 
 
 
 
 
 
 
 
 

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Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
SMART Registry 
 
CLINICAL INVESTIGATION PLAN 
 
Study Reference Number: C1949 
 
Sponsored By 
Boston Scientific, CRM  
4100 Hamline Ave. N. 
St. Paul, MN 55112 
 
and 
 
Guidant Europe SA / NV, 
a Boston Scientific Company 
 CRM Clinical Department  
Green Square 
Lambroekstraat 5D  
1831 Diegem,  
Belgium 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contacts 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
Coordinating Principal 
Investigator 
Prof. Dr. Ignacio García Bolao 
Clínica Universitaria de Navarra 
Avda. de Pío XII, 36 
31008 Pamplona,  
Navarra, Spain 
 
Vendors/Labs 
A list of vendors/laboratories involved in the trial is maintained by 
the sponsor.  
 
 
 

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Original Release: January, 20, 2017 
Current Version: February, 06, 2017 
 
Revision History 
Revision Number 
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for Change 
AA 
20-JAN-2017 
90702637 
Rev./Ver. AH 
N/A 
Original Release 
 
B 
06-FEB-2017 
90702637 
Rev./Ver. AH 
Cover Page 
Header 
SMART CRT Registry 
Protocol by SMART 
Registry Protocol 
No CRT mention 
required 
B 
06-FEB-2017 
90702637 
Rev./Ver. AH 
Page 29 
Header 
SMART CRT Registry 
Protocol SMART 
Registry Protocol 
No CRT mention 
required 
 
 

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2. Protocol Synopsis 
Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
SMART Registry 
Study 
Objective(s) 
To learn in a general Cardiac Resynchronization Therapy Defibrillators 
(CRT-D) population, which optimization techniques are used and how 
effective they are. It will compare 12-month response rates among 
different optimization methods and characterize which selected subject 
subgroups achieve better response than others. 
 
A subset of SMART Registry subjects will contribute to the NG4 Post 
Market Clinical Follow Up (PMCF) Cohort whose objective is collecting 
data on the NG4 CRT-D features and device usage in a real world setting 
and monitor long term safety associated with these devices to support CE 
Mark. 
Planned 
Indication(s) for 
Use  
All implanted devices will be used within the current labeled indications 
for use. CRT-D devices are intended to provide cardiac resynchronization 
therapy and provide anti-tachycardia pacing and defibrillation therapy. 
Test Device 
The quadripolar BSC CRT-D models in the NG3 family (AUTOGEN, 
INOGEN and DYNAGEN families) used in the study are approved for 
commercial use. Future generation of quadripolar BSC CRT-D models in 
the NG4 family (RESONATE MOMENTUM, CHARISMA and 
VIGILANT) will be used in the study once approval by the local 
regulatory body will be obtained.  
Although the NG4 family of models (with the exception of CHARISMA) 
may become approved in the US during the study, the RESONATE, 
MOMENTUM, VIGILANT families of devices are not to be used in the 
SMART Registry in the US until device approval is received by FDA and 
the devices are available at the participating sites.  
All CRT-D devices utilized in the study include LV VectorGuide™ and 
SmartDelay™ features.  
The Left Ventricular MultiSite Pacing (LV MSP) feature is available in 
the NG4 family of CRT-D devices (RESONATE HF, RESONATE, 
CHARISMA VIGILANT, and MOMENTUM devices).  
These devices have quadripolar headers and accept LV quadripolar leads 
according to the corresponding Physician Technical Manual  

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Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
SMART Registry 
Planned 
Number of 
Participating 
Sites / Countries 
A maximum of 200 sites in Europe, United States, Canada and Asia-
Pacific region. 
Primary 
Endpoint(s) 
CRT Response rate at 12 months, defined by a Clinical Composite Score 
(Full Registry). 
 All-cause mortality  
 Heart failure events  
 NYHA Class  
 Quality of life (Patient Global Assessment instrument)  
NG4 PMCF 
Endpoint 
The Post Market Clinical Follow Up (PMCF) endpoint is NG4 PG 
Related Complication Free rate at 36 months (NG4 PMCF Cohort only). 
Additional 
Endpoints 
Multivariate analyses to determine which covariates and optimization 
methods are associated with response (Full Registry) 
Method of 
Assigning 
Patients to 
Treatment 
Subjects implanted with a qudripolar NG3 or NG4 CRT-D device in 
conjunction with a quadripolar lead from any manufacturer will be 
selected based on the inclusion/exclusion criteria and if deemed to be 
eligible for participation, will be asked to sign the informed consent form. 
Subjects who meet the eligibility criteria and have signed and dated the 
Informed Consent Form are considered enrolled in the study. 
Follow-up 
Schedule 
Each enrolled subject will be followed at the at the following visits: 
 Enrollment and consent at post implant visit 
 12 months Clinic Visit (per site Standard of Care) 
NG4 PMCF Cohort will be followed additionally at: 
 24 months Clinic Visit 
 36 months Clinic Visit 
 Annually until the last PMCF cohort subject has completed 36 
months visit. 
There are no other additional study-related visits required. Additional 
visits occurred per the site Standard of Care (SOC) in the first 12 months 
of follow up may be collected. 

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Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
SMART Registry 
Study Duration 
The study duration is estimated to be approximately 6 years from first 
enrollment to study closure. Each subject will be followed for a minimum 
of 12 months.  
 NG4 PMCF Cohort will be followed until the last actively 
followed PMCF subject achieves 36 months of follow-up.  
The study will be considered complete after the last actively followed 
subject from the NG4 PMCF Cohort of subjects achieves 36 months of 
follow up or the last actively followed subject from the full registry 
achieves 12 months of follow up, whichever happens later. 
Key Inclusion 
Criteria 
 Subject implanted or upgraded with a NG3 or NG4 CRT-D device 
connected with any manufacturer quadripolar LV lead based on 
BSC labeling for devices in specific geographies. 
 Subjects must be enrolled between 1 and 21 calendar days post 
CRT-D implantation procedure. 
 Subject is age 18 or above, or of legal age to give informed 
consent specific to each country and national laws  
 Subject is willing and capable of complying with follow-up visits 
and procedures as defined by this protocol 
Key Exclusion 
Criteria 
 Subject with documented life expectancy of less than 12 months  
 Subject currently on the active heart transplant list or has a current 
Left Ventricular Assist Device or other assist device (mechanical 
circulatory support device).  
 Subject who have had a pre-existing CRT device  
 Subject enrolled  in any other concurrent clinical trial without 
prior written approval from BSC Clinical Trial Manager 
 Women of childbearing potential who are or might be pregnant at 
time of study enrolment  
 Any contra-indication to receive a CRT-D device per local 
guidelines 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
The proposed observational study (Registry) does not have formal 
hypothesis testing and is exploratory in nature. 
Statistical Test 
The Clinical Composite Score allows for three levels of CRT Response: 
Improved, Unchanged or Worsened. The number and percent of SMART 

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Strategic MAnagement to Optimize Response To Cardiac 
Resynchronization Therapy Registry 
SMART Registry 
Method 
Registry subjects contributing to each level of CRT Response will be 
calculated. 
CRT Response rates will be compared between selected subgroups. Due 
to the ordinal nature of the three CRT response levels defined by the 
Clinical Composite Score, statistical tests accounting for ordinality of 
response will be used, when appropriate.  In analyses comparing two 
subgroups, a Cochran-Armitage test for trend will be employed.  If more 
than two subgroups will be compared, a cumulative logit model or some 
other appropriate test will be used.  
Sample Size 
Parameters 
Due to a lack of hypotheses for this objective, the sample size cannot be 
determined through traditional statistical powering techniques.  It is, 
however, desired to have a high degree of confidence in the CRT 
Response rates obtained in the study. In order to obtain a two-sided 95% 
confidence interval width of the overall SMART Registry CRT Response 
rate that does not exceed 5%, a total of 2000 subject enrollments are 
required.  Additionally, it is expected that with a total of 2000 
enrollments, each subgroup analysis will include a sufficient sample of 
approximately 50 subjects 

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3. Table of Contents 
1. 
TITLE PAGE  ........................................................................................................................ 1 
3.1. Table of Figures ...................................................................................................... 13 
3.2. Table of Tables ....................................................................................................... 13 
5.1. CRT-D Device ......................................................................................................... 17 
5.1.1. 
LV VectorGuide™ .................................................................................... 18 
5.1.2. 
SmartDelay™ ............................................................................................ 19 
5.1.3. 
LV MultiSite Pacing .................................................................................. 19 
5.1.4. 
HeartLogic™ Index ................................................................................... 20 
5.2. Other Devices .......................................................................................................... 21 
8.1. Scale and Duration ................................................................................................. 22 
8.2. Treatment Assignment .......................................................................................... 23 
8.2.1. 
Treatment and Control ............................................................................... 24 
8.3. Justification for the Study Design ......................................................................... 24 
9.1. Study Population and Eligibility ........................................................................... 24 
9.2. Inclusion Criteria ................................................................................................... 25 
9.3. Exclusion Criteria .................................................................................................. 25 
10.1. Point of Enrollment ................................................................................................ 26 
10.2. Withdrawal ............................................................................................................. 26 
10.3. Subject Status and Classification .......................................................................... 27 
10.4. Enrollment Controls .............................................................................................. 27 
11.1. Data Collection ....................................................................................................... 27 
11.2. Study Candidate Screening ................................................................................... 30 
11.3. Informed Consent .................................................................................................. 30 
11.4. Enrollment Visit - Index Visit (Day 0) ................................................................. 30 
11.4.1. Inclusion and Exclusion Criteria ............................................................... 31 
11.4.2. Subjects Demographics ............................................................................. 31 
11.4.3. Medical History ......................................................................................... 31 
11.4.4. Subject Physical Assessment ..................................................................... 31 
11.4.5. NYHA Class Assessment .......................................................................... 32 
11.4.6. Cardiac Medications .................................................................................. 32 
11.4.7. Implanted System Information .................................................................. 32 

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 LV Lead Location ..................................................................... 32 
11.4.7.1.
11.4.8. Current Device Setting and Status ............................................................. 33 
11.4.9. Battery Consumption ................................................................................. 33 
11.4.10. Lead Measurements ................................................................................... 33 
11.4.11. Optimization features information ............................................................. 34 
 SmartDelay Feature Data .......................................................... 34 
11.4.11.1.
 LV VectorGuide feature Data ................................................... 34 
11.4.11.2.
 LV MSP feature Data ................................................................ 35 
11.4.11.3.
 HeartLogic feature Data ............................................................ 36 
11.4.11.4.
 Other optimization methods information .................................. 36 
11.4.11.5.
11.4.12. Final Device Settings and Status ............................................................... 36 
11.4.13. Adverse Events Assessment ...................................................................... 36 
11.5. 12 months Clinic Visit ............................................................................................ 37 
11.5.1. Subject Physical assessment ...................................................................... 38 
11.5.2. Cardiac Medication Changes ..................................................................... 38 
11.5.3. NYHA Class Assessment .......................................................................... 38 
11.5.4. Physician Global Assessment .................................................................... 38 
11.5.5. Patient Global Assessment ........................................................................ 38 
11.5.6. Definition and Components of the Clinical Composite Score ................... 39 
 HF Hospitalization Definition................................................... 39 
11.5.6.1.
 PGA Classification.................................................................... 39 
11.5.6.2.
 CCS Status Classification ......................................................... 39 
11.5.6.3.
11.5.7. Current Device Settings and Status ........................................................... 40 
11.5.8. Changes in programming since the last Clinic Visit ................................. 40 
11.5.9. SmartDelay test and value ......................................................................... 40 
11.5.10. LV VectorGuide test and value ................................................................. 40 
11.5.11. SmartVector and SmartOffset value .......................................................... 40 
11.5.12. Current device setting and status ............................................................... 40 
11.5.13. Battery Consumption ................................................................................. 40 
11.5.14. Lead Measurements ................................................................................... 41 
11.5.15. Optimization information .......................................................................... 41 
11.5.16. Final Device Settings and Status ............................................................... 41 
11.5.17. Adverse Events Assessment ...................................................................... 41 
11.6. Additional SOC Clinic Visits ................................................................................ 41 
11.7. 24 months Clinic Visit, 36 months Clinic Visit and Annual Clinic Visits ......... 42 
11.7.1. NYHA Class Assessment .......................................................................... 43 
11.7.2. Cardiac Medication Changes ..................................................................... 43 
11.7.3. Current device setting and status ............................................................... 43 
11.7.4. Changes in programming since the last Study Clinic Visit ....................... 43 

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11.7.5. Battery Consumption ................................................................................. 44 
11.7.6. Lead Measurements ................................................................................... 44 
11.7.7. LV MSP feature Data ................................................................................ 44 
11.7.8. HeartLogic feature Data ............................................................................ 44 
11.7.9. Final Device Settings and Status ............................................................... 44 
11.7.10. Adverse Events Assessment ...................................................................... 44 
11.8. Study Completion ................................................................................................... 45 
12.1. Endpoints ................................................................................................................ 45 
12.1.1. Primary Endpoint ....................................................................................... 45 
12.1.2. SMART Registry Primary Endpoint ......................................................... 45 
 Hypotheses ................................................................................ 45 
12.1.2.1.
 Sample Size ............................................................................... 45 
12.1.2.2.
 Statistical Methods .................................................................... 45 
12.1.2.3.
12.1.3. NG4 PMCF Endpoint ................................................................................ 46 
 Hypotheses ................................................................................ 46 
12.1.3.1.
 Hypotheses ................................................................................ 46 
12.1.3.2.
 Sample Size ............................................................................... 47 
12.1.3.3.
 Statistical Methods .................................................................... 47 
12.1.3.4.
12.2. General Statistical Methods .................................................................................. 47 
12.2.1. Analysis Sets .............................................................................................. 47 
12.2.2. Control of Systematic Error/Bias ............................................................... 47 
12.2.3. Number of Subjects per Investigative Site ................................................ 47 
12.3. Data Analyses ......................................................................................................... 47 
12.3.1. Other Endpoints/Measurements ................................................................. 47 
12.3.2. Interim Analyses ........................................................................................ 48 
12.3.3. Subgroup Analyses .................................................................................... 49 
12.3.4. Justification of Pooling .............................................................................. 49 
12.3.5. Changes to Planned Analyses .................................................................... 49 
13.1. Data Collection, Processing, and Review ............................................................. 50 
13.2. Data Retention ........................................................................................................ 50 
16.1. Statement of Compliance ....................................................................................... 51 
16.2. Investigator Responsibilities ................................................................................. 51 
16.2.1. Delegation of Responsibility ..................................................................... 53 
16.3. Institutional Review Board/ Ethics Committee ................................................... 53 
16.4. Sponsor Responsibilities ........................................................................................ 53 
16.4.1. Role of Boston Scientific Representatives ................................................ 54 
16.5. Insurance ................................................................................................................. 55 

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18.1. Anticipated Adverse Events .................................................................................. 55 
18.2. Anticipated Adverse Device Effects ...................................................................... 57 
18.3. Risks Associated with the Study Device(s) ........................................................... 57 
18.4. Risks associated with Participation in the Clinical Study .................................. 57 
18.5. Risk Minimization Actions .................................................................................... 57 
18.6. Anticipated Benefits ............................................................................................... 57 
18.7. Risk to Benefit Rationale ....................................................................................... 57 
19.1. Reportable Events by investigational site to Boston Scientific .......................... 58 
19.2. Definitions and Classification ............................................................................... 59 
19.3. Relationship to Study Device(s) ............................................................................ 62 
19.4. Investigator Reporting Requirements .................................................................. 64 
19.5. Boston Scientific Device Deficiencies .................................................................... 65 
19.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................... 66 
19.7. Subject Death Reporting ....................................................................................... 66 
21.1. Safety Monitoring Process ..................................................................................... 68 
21.2. Steering  Committee ............................................................................................... 68 
22.1 Premature Termination of the Study ................................................................... 68 
22.1.1 
Criteria for Premature Termination of the Study ....................................... 68 
22.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC Approval .................................................................................................. 69 
22.3 Requirements for Documentation and Subject Follow-up ................................. 69 
22.4 Criteria for Suspending/Terminating a Study Site ............................................. 69 
24.1. Subject Reimbursement ........................................................................................ 70 
24.2. Compensation for Subject’s Health Injury ......................................................... 70 
26.1. Detailed steps on obtaining the data from the SmartDelay test ........................ 73 
26.2. Detailed steps on obtaining the data from the LV VectorGuide test ................ 74 
26.3. Detailed steps on running SmartVector test ........................................................ 75 
26.4. Detailed steps on running SmartOffset test ......................................................... 75 
27.1. Abbreviations ......................................................................................................... 76 
27.2. Definitions ............................................................................................................... 78 
 
 
 

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3.1. Table of Figures 
Figure 1: Clinical Composite Events results for clinical trials used to support regulatory 
approvals of CRT devices or expanded indications ............................................ 15 
Figure 2: LV VectorGuide Screen Example ........................................................................... 18 
Figure 3: SmartDelay Screen Example ................................................................................... 19 
Figure 4: LATITUDE NXT 5.0 System ................................................................................. 20 
Figure 5: SMART Registry Study Design .............................................................................. 23 
 
3.2. Table of Tables 
Table 5.1-1: Eligible CRT-D Device Model ........................................................................... 17 
Table 9.2-1: Inclusion Criteria ................................................................................................ 25 
Table 9.3-1: Exclusion Criteria ............................................................................................... 25 
Table 11.1-1: Data Collection Schedule ................................................................................. 29 
Table 11.4-1: NYHA Classifications ...................................................................................... 32 
Table 11.4-2: Source Documentation Required at Enrollment Visit ...................................... 36 
Table 11.5-1: Global Assessment Tool: Physician Global Assessment (PhGA) and Patient 
Global Assessment (PGA) ................................................................................... 38 
Table 11.5-2: Source Documentation required at 12 months Clinic Visit .............................. 41 
Table 11.6-1: Source Documentation Required at Additional SOC Clinic Visits .................. 42 
Table 11.7-1: Source Documentation Required at 24, 36 months and Annual Clinic Visit ... 44 
Table 18.1-1: Potential Adverse Events for Implantation of a Pulse Generator and/ or Lead 
System .................................................................................................................. 56 
Table 19.2-1: Safety Definitions ............................................................................................. 59 
Table 19.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 63 
Table 19.4-1: Investigator Reporting Requirements ............................................................... 64 
Table 26.1-1: Abbreviations ................................................................................................... 76 
Table 26.2-1: Definitions ........................................................................................................ 78 
 

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4. Introduction 
Heart failure may be exacerbated by the presence of an interventricular conduction delay. 
This delay in conduction, evidenced by a wide QRS pattern on an ECG, results in an 
inefficient asynchronous contraction pattern. Cardiac resynchronization therapy (CRT) is the 
application of electrical stimuli to both ventricles with an implanted device.   
Cardiac resynchronization therapy, when combined with defibrillation (CRT-D) was first 
demonstrated to be safe and effective in the CONTAK CD study1. This study showed that 
defibrillator subjects with NYHA Class III-IV heart failure, reduced ejection fraction, and 
wide QRS who randomized to CRT-D On had significantly improved exercise performance, 
reduction in symptoms, increased quality of life, and improved cardiac structure and function 
when compared to subjects randomized to CRT-D Off.   
The COMPANION study was a subsequent study of subjects NYHA Class III-IV heart 
failure, reduced ejection fraction, and wide QRS. Unlike the prior CONTAK CD study, 
subjects in COMPANION were not indicated for a defibrillator.  Subjects in this study were 
randomized on a 2:2:1 basis to CRT-D, CRT-P (CRT without a defibrillator), or optimal 
pharmacological therapy. COMPANION not only confirmed the results from the CONTAK 
CD study, but demonstrated additional benefits of CRT that included significant reduction in 
all-cause mortality, both alone and in combination with hospitalization due to all-causes, 
cardiovascular causes, or heart failure2.   
The study of CRT-D was extended in the MADIT CRT trial to defibrillator subjects with 
NYHA Class I-II, reduced ejection fraction, and wide QRS. Like the COMPANION study 
before it, MADIT CRT showed that CRT-D was associated with significant reduction in all-
cause mortality, alone and in combination with heart failure hospitalization when compared 
to subjects receiving a defibrillator alone3. MADIT CRT also demonstrated significant 
reduction in left ventricular volumes and improvement in left ventricular ejection fraction. 
The benefits of CRT-D are not conferred on every subject implanted with a device, 
however.  Subjects who fail to show improvement are typically referred to as “non-
responders”. There is no universally accepted metric for defining response. Commonly used 
outcome measures in clinical practice include symptomatic relief, quality of life, or exercise 
tolerance. Improvements in echocardiographic parameters (left ventricular 
dimensions/volumes and left ventricular ejection fraction) may also be used. Large scale 
clinical trials tend to use composite endpoints, of which the Clinical Composite Score (CCS) 
first described by Milton Packer is the most widely used4. This endpoint combines four 
metrics: all-cause mortality, heart failure hospitalization, NYHA Class, and quality of life as 
measured with the patient global assessment instrument. When clinical metrics are used, the 
typical non-response rate cited is one-third of patients are non-responders.  When echo-based 
measures are used, the non-response rate is somewhat higher. 
Figure 1 below summarizes the Clinical Composite Endpoint (CCE) results for clinical trials 
that were used to support regulatory approvals of CRT devices or expanded indications. 
Approximately two-third of Class III-IV patients are responders. Class I-II patients have not 
been studied as extensively and have response rates about 10 percentage points lower. This 
disparity is likely due to the less severe nature of heart failure in Class I-II patients. Since 

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they are less symptomatic than Class III-IV patients, demonstrating improvement is more 
difficult. For these patients, maintaining the status quo may be a more appropriate therapeutic 
goal. In these patients, approximately 80% either improve or maintain their heart failure 
status. 
 
Figure 1: Clinical Composite Events results for clinical trials used to support regulatory 
approvals of CRT devices or expanded indications 
 
The potential reasons for non-response are varied and include5: 
 Poor or wrong lead 
location 
 Improper 
programming 
 Myocardial scar 
 Lack of baseline 
dyssynchrony 
 Irreversibily 
advanced heart failure 
 Atrial fibrillation 
 
Several strategies have been tested in attempt to identify and reduce the number of non-
responders.  Such strategies include post hoc analyses of left ventricular (LV) lead 
placement, pacing at sites of maximal electrical or mechanical delay/dyssynchrony and the 
use of device-based optimization features. The results of these studies have identified several 
factors that may impact response. For instance, left ventricular pacing in apical regions is 
deleterious, whereas pacing at sites of late electrical or mechanical delay is associated with 
better outcomes.6-14 
Device-based features have been introduced that modify how CRT is delivered. These 
include: 

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 Interventricular timing (V-V timing) 
 AV Delay 
 Multi-site pacing 
 LV-only CRT 
To date, the randomized clinical studies conducted have shown equivalence with 
conventional CRT delivery without demonstrating superiority although subsequent subgroup 
analyses suggest that some patients may be helped. 
V-V Timing:  The InSync III Marquis Study15 using the CCE, DECREASE HF Study16 using 
a composite of peak VO2 and LVESD, and RHYTHM ICD V-V Optimization Study17 using 
peak VO2 all demonstrated the safety of this feature and non-inferiority to conventional 
sequential biventricular pacing, but none showed superiority. 
LV Only CRT:  The DECREASE HF Study16 using a composite of peak VO2 and LVESD 
and the B-LEFT HF Study18 using the CCE demonstrated safety of LV pacing but neither 
showed that LV Only CRT was superior to conventional biventricular CRT.  The 
AdaptivCRT study, using the CCE, evaluated an algorithm that provided either LV or 
biventricular pacing depending on AV conduction while also periodically adjusting AV delay 
and V-V timing.  This algorithm was found to be non-inferior to echocardiographic-guided 
optimization19. 
AV Delay: Randomized studies to determine the effectiveness of optimizing AV delay have 
been based on algorithms that use measurements of intrinsic conduction to establish an AV 
delay. These studies include FREEDOM20 (which also included a V-V timing optimization 
algorithm) and used the CCE and SMART-AV21 which used LVESV, which showed these 
methods were non-inferior to empiric programming. The RESPOND-CRT study, which 
evaluated a CRT system that employed a hemodynamic sensor to optimize both AV and VV 
timing, used a modified version of the CCE. This study as well found that the sensor was 
non-inferior to echocardiographic optimization22. 
Left Ventricular Multi-Site Pacing: Left ventricular Multi-Site Pacing (LV MSP) has 
emerged as an option for addressing the non-responder issue with conventional CRT by 
using a quadripolar lead to pace two sites within the same coronary vein. Studies have shown 
that LV MSP improved acute hemodynamics and ventricular synchrony, and resulted in 
faster activation of myocardium and improved clinical responses as measured by the 
ventricular reverse remodeling and LVEF value comparing to single site LV pacing23-31. 
Furthermore, acute studies on LV MSP have shown no ventricular arrhythmias or other 
adverse events during acute testing, implant and pre-discharge27. 
Among different LV MSP configurations discussed in the literature, pacing from two sites 
that are farthest apart (distal to proximal) was the most common optimal configuration as it 
may recruit a larger area of the myocardium with late activation to achieve better ventricular 
synchrony15, 19. Opting for the two pacing sites that are farthest apart may provide a simple 
means for pacing vector selection in MSP, in combination with the evaluation of pacing 
threshold and impedance, and the avoidance of the phrenic nerve stimulation (PNS).   
The Multi-Point Pacing (MPP) Trial32, using a modified version of the CCS, evaluated a 
CRT-D system that paced the left ventricle from two distinct sites using a quadripolar lead. 
The study had a 3 month run-in phase that identified non-responders who were then 
randomized to MPP or conventional CRT. The MPP Trial provided safety data of the MPP 

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5.1.2. SmartDelay™ 
The SmartDelay optimization feature quickly (<2.5 minutes) provides recommended settings 
for programming paced and sensed AV Delay based on the measurement of intrinsic AV 
intervals. The objective of the feature is to recommend AV Delays that provide optimally 
timed CRT, which maximizes contractile function.  
The SmartDelay optimization test evaluates right and left ventricular response to both atrial 
sensed and paced events to determine suggested settings for the following: Paced AV Delay 
(PAV), Sensed AV Delay (SAV), pacing chamber(s).  
 
Figure 3: SmartDelay Screen Example 
 
5.1.3. LV MultiSite Pacing 
Among new features available in the NG4 CRT-D devices is the Left Ventricular MultiSite 
Pacing (LV MSP). 
The LV MSP feature allows the clinician to program cardiac resynchronization therapy 
(CRT) to deliver two LV paces per cardiac cycle during Normal Brady operation which is 
different compared with traditional CRT with one LV pace per cardiac cycle. Each of the LV 
paces has its own independently programmable pacing vector and LV MSP provides the 
clinician the ability to control the timing between the ventricular paces.  
The clinician can program Pacing Chamber so that the system delivers CRT pacing therapy 
to both ventricular chambers (BiV Pacing) or to just the left ventricular chamber (LV Only).   
 

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5.1.4. HeartLogic™ Index 
Among new features available in some of the NG4 CRT-D devices is the HeartLogic™ Heart 
Failure Diagnostic Service (HeartLogic). HeartLogic is comprised of a composite trend 
called the HeartLogic Index, a configurable yellow Alert, and the device measured Heart 
Sounds trends. These alerts are all delivered via BSC LATITUDE™ NXT 5.0 System 
(LATITUDE) (or equivalent) remote monitoring system. The HeartLogic Index and Alert are 
a validated diagnostic tool to detect gradual worsening of heart failure (HF) over days or 
weeks using multiple physiologic measurements (accepted for publication).   
The HeartLogic Index aggregates measurements from multiple device-based sensors (Heart 
Sounds, Thoracic Impedance, Respiration, and Night Heart Rate) and reflects changes over 
time in the subject’s sensor trend data from their respective baseline values. HeartLogic 
provides additive information for clinicians to use in context with standard-of-care patient 
treatment and should not replace standard-of-care treatment. 
The CRT-D device, along with its associated leads, constitutes the implantable portion of the 
system. The external portion of the system includes the commercially available LATITUDE 
System (or equivalent) and the Model 3120 Programmer Recorder Monitor (or equivalent). 
The external portion of the system allows interrogation and programming of the PG, as well 
as access to the PG’s diagnostic features. Communication between the internal and external 
portions of the system is conducted through a handheld wand and/or wireless telemetry. Data 
are then transmitted to the clinician care team. The complete LATITUDE system is shown in 
Figure 4. When the subject is near the LATITUDE communicator, data will automatically be 
uploaded and transmitted to the clinician for review. When the HeartLogic index is met or 
exceeded, a yellow alert is generated which triggers health care professional to review the 
data and contact the subject.      
 
Figure 4: LATITUDE NXT 5.0 System 
 

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5.2. Other Devices 
Any commercially available Right Atrial (RA) lead, Right Ventricular (RV) lead and 
quadripolar LV lead from any manufacturer is eligible in the study.  
 
6. Study Objectives 
The primary objective in this study is to learn in a general CRT-D population, which 
optimization techniques are used and how effective they are. It will compare 12-month 
response rates among different optimization methods and characterize which selected patient 
subgroups achieve better response than others. 
A subset of SMART Registry subjects will contribute to the NG4 Post Market Clinical 
Follow-Up (PMCF) Cohort whose objective is collecting data on the NG4 CRT-D features 
and device usage in a real world setting and monitor long term safety associated with these 
devices to support CE Mark. 
7. Study Endpoints 
The primary endpoint will evaluate the CRT Response rate among Full Registry subjects at 
12 months, defined by a Clinical Composite Score (CCS) consisting of: 
 All-cause mortality  
 Heart failure events  
 NYHA Class  
 Quality of life (patient Global Assessment instrument)  
 
For the NG4 PMCF Cohort the primary endpoint will be NG4 PG related complication free 
rate at 36 months. 
 
SMART Registry Entire Cohort 
The Clinical Composite Score developed by Packer will be evaluated to determine CRT 
Response in the entire SMART Registry cohort and in selected subgroups4, 17. The CCS will 
be evaluated at 12 months and consists of all-cause mortality, heart failure events, NYHA 
class and quality of life as assessed by the patient Global Assessment instruction.  CRT 
response status for each subject will be determined by the CCS, with CRT response classified 
as improved, unchanged or worsened.   
 
NG4 PMCF Cohort 
In the subjects included in the NG4 PMCF Cohort, the NG4 PG-related complication free 
rate (CFR) at 36 months will be evaluated. The PMCF Primary Endpoint will evaluate the 
safety of the NG4 device when LV MSP is enabled. 

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8. Study Design 
This is a global, multicenter, prospective, observational, single-arm post market study 
(Registry), including the NG4 PMCF necessary to support NG4 CE Mark. 
8.1. Scale and Duration 
The study will be conducted at up to 200 sites globally. Approximately 2000 subjects will be 
enrolled in Europe, United States, Canada and Asia Pacific, and sites may continue to enroll 
subjects until notified of enrollment completion.   
SMART Registry Entire Cohort 
Enrollments are expected to occur over a period of approximately 28 months. Subjects 
enrolled in the SMART Registry will be followed for12 months.  
NG4 Post-Market Clinical Follow-up Cohort 
The NG4 PMCF subjects will be enrolling exclusively from European participating sites and 
will be followed for a minimum of 36 months.  
The SMART Registry and NG4 PMCF Cohort are expected to be completed in 
approximately 6 years.   
 
 
 

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eligible BSC CRT-D device and a compatible quadripolar LV lead according to their 
corresponding Physician Technical Manual  
 
8.2.1. Treatment and Control 
Subjects will not be randomized or blinded to treatment received. Any subject meeting all 
inclusion and no exclusion criteria is enrollment eligible for the SMART Registry. Subjects 
are considered enrolled in the study once the informed consent form (ICF) has been 
executed. 
8.3. Justification for the Study Design 
While a randomized study is considered the gold standard in many clinical research settings, 
considering the sample size and study objectives, a non-randomized, observational study 
with up to 2000 subjects is considered appropriate to meet the objectives of the study. In 
order to obtain a “real world” picture of the device use, inclusion and exclusion criteria and 
follow up schedule has been written generally enough to allow for study center specific 
standard of practice that should accurately capture the device use in a “standard” clinical 
setting.  
Additionally by requiring the study centers to follow their specific standard of practice, risk 
to the subject is minimized because the treatment received by the subject will be similar to 
the treatment the subject would receive if not participating in the study. 
The SMART Registry is a global, multicenter, prospective, observational, single-arm post 
market study (registry), including a European, multicenter, prospective, single-arm sub-study 
(NG4 PMCF). The objective of the SMART Registry is to characterize rates of CRT 
response in a general CRT-D population as well as in selected subgroups defined by device 
and subject characteristics.   
It is desired to have a high degree of confidence in the CRT response rates obtained in the 
study. To obtain a two-sided 95% confidence interval width of the CRT response rate that 
does not exceed 5%, a total of 2000 subject enrollments are required. Additionally, it is 
expected that with a total of 2000 enrollments, each subgroup analysis will include 
approximately 50 subjects. 
A minimum of 103 NG4 PMCF subjects are required to sufficiently power the PMCF 
endpoint. 
The primary objective of the NG4 PMCF sub-study is to gather data to establish the chronic 
safety, performance and effectiveness of NG4 CRT-D devices. 
9. Subject Selection  
9.1. Study Population and Eligibility  
Subjects included in the SMART Registry should be selected from the investigator’s general 
patient population of subjects who are indicated for CRT-D implantation per BSC labeled 

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indication provided in Section 9.2. Investigators are responsible for screening all potential 
subjects and selecting those who meet the eligibility criteria for the study as described in 
Sections 9.2 and Section 9.3 below. Investigators are encouraged to include consecutive 
subjects in order to minimize selection biases. 
 
9.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 9.2-1) may be given consideration 
for inclusion in this Registry, provided no exclusion criterion (see Section 9.3) is met.  
Table 9.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
 Subject implanted or upgraded with an NG3 or NG4 CRT-D device 
based on BSC labelling for devices in specific geographies in 
conjunction with a quadripolar LV lead from any manufacturer 
 Subjects must be enrolled between 1 and 21 calendar days post CRT-
D implantation procedure 
 Subject is age 18 or above, or of legal age and willing and capable to 
provide informed consent specific to each country and national laws  
 Subject is willing and capable of providing informed consent 
 
Subject is willing and capable of complying with follow-up visits and 
procedures as defined by this protocol 
 
 
9.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 9.3-1) will be excluded from this 
clinical study. 
Table 9.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
 Subject with documented life expectancy of less than 12 months  
 Subject currently on the active heart transplant list or has a current 
Left Ventricular Assist Device or other assist device.  
 Subject who have had a pre-existing CRT device  
 Subject Enrolled  in any other concurrent clinical trial without prior 
written approval from BSC Clinical Trial Manager 
 Women of childbearing potential who are or might be pregnant at 
time of study enrolment  
 Any contra-indication to receive a CRT-D device per local guidelines 
 

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10. Subject Accountability 
10.1. Point of Enrollment 
Investigators will select subjects who are appropriate for study inclusion as per eligibility 
criteria. Subjects who meet the eligibility criteria and agree to participate will be given 
written informed consent approved by the center’s Institutional Review Board (IRB) / Ethics 
Review Committee (ERC). 
All subjects who complete the informed consent process, sign and date the informed consent 
form (ICF) are considered enrolled in the SMART Registry. Subjects who have signed the 
informed consent but are found to not meet eligibility criteria at the time of enrollment are 
classified as consent ineligible. No study related procedures or data collection can take place 
until the ICF is executed. Screening tests that are part of Standard of Care (SOC) can be used 
to determine pre-eligibility. Subjects enrolled in this registry must be followed per this 
protocol.  
Subjects will be enrolled at post implant (between 1 and 21 calendar days post CRT-D 
implantation procedure). 
SMART Registry subject is considered as part of the NG4 PMCF Cohort when enrolled in a 
European site, has an NG4 device implanted and LV MSP feature is enabled.  
10.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) shall be accounted for and documented. If a subject withdraws from this 
registry, the reason(s) shall be reported. If such withdrawal is due to problems related to 
device safety or performance, the investigator shall ask for the subject’s permission to follow 
his/her status/condition outside of the clinical study.  
 
Reasons for withdrawal include, but are not limited to:  
o Subject found not to meet eligibility criteria 
o Subject choice to withdraw consent 
o PI decision to withdraw the subject 
o Device explanted and not replaced with an NG3/NG4 CRT-D system 
o Implanted system element not active (IPG, RA lead, RV lead and quadripolar LV 
lead) 
o Use of epicardial lead 
o Ventricular Assist Device insertion or heart transplant  
o Lost to follow-up, despite best efforts to locate the subject; 
 Three documented attempts to contact the subject are required to declare a 
subject lost to follow up. 
o Death (see Section 19.7 for reporting requirements) 
 
If a subject withdraws from the clinical investigation, the reason(s) shall be reported on the 
corresponding eCRF of the EDC system. Data up to the point of withdrawal will be collected 
and may be used. All open adverse events should be closed or documented as chronic.  

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10.3. Subject Status and Classification 
Enrolled Subjects will be classified in the study as follows: 
 Consented and ineligible - A study subject who has signed informed consent form 
(ICF) but is found to not meet eligibility criteria will be considered a consent 
ineligible subject and will not count towards the enrollment ceiling. There are no 
follow-up or adverse event reporting requirements for consent ineligible subjects. The 
original signed ICF must be maintained in the center’s administrative file. 
 Actively Enrolled (Consented and eligible) - subjects who have signed the ICF, meet 
all inclusion criteria and do not meet any of the exclusion criteria. These subjects will 
be followed in accordance with Clinical Investigational Plan (CIP) follow up 
schedule and included in the future study analysis. The original signed ICF must be 
maintained in the center’s administrative file. All applicable case report forms per the 
CIP must be completed.  
 NG4 PMCF Cohort - will be a minimum of the first 103 European subjects identified 
by the Sponsor enrolled in the SMART Registry, implanted with an NG4 device and 
that had LV MultiSite feature enabled at any time during the initial 12 months follow 
up.  
10.4. Enrollment Controls 
Approximately 2000 subjects will be enrolled in the SMART Registry. Study sites will be 
notified when the enrollment is complete. No single site shall enroll more than 20% subjects 
to mitigate any bias from a single center in final study analysis without the prior written 
approval from BSC Clinical Trial Manager. 
NG4 PMCF Cohort will be completed as soon as a minimum of the first 103 European 
subjects identified by the Sponsor enrolled in the SMART Registry, implanted with an NG4 
device and that had LV MultiSite feature enabled at any time during the initial 12 months 
follow up.  
Once the NG4 PMCF Cohort has been completed, a notification will be submitted to all 
European sites confirming that no additional subjects are required to be identified to be 
followed more than 12 months. 
 
11. Study Methods 
11.1. Data Collection 
The data collection schedule is shown in Table 11.1-1. 
SMART Registry subjects: 
 

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o Enrollment and consenting visit at Post-Implant (between 1 and 21 calendar days 
after CRT-D implantation procedure) (Required) 
o 12 months Clinic Visit (330-390 calendar days from enrollment date) (Required) 
o Additional Standard of Care (SOC) Visits 
 
NG4 PMCF Cohort: Only for the identified NG4 PMCF Cohort: 
 
In addition to complete all standard SMART Registry Clinic Visits stated above, NG4 PMCF 
subjects will have to complete the following Clinic Visits: 
 
o 24 months Clinic Visit (690-750 calendar days from enrollment date) (Required) 
o 36 months Clinic Visit (1050-1110 calendar days from enrollment date) 
(Required) 
o Annual Follow-Up Visit after 36 months and until last PMCF subject will 
complete the 36 months Clinic Visit (Required) 

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Table 11.1-1: Data Collection Schedule 
 
SMART Registry 
Only NG4 PMCF subjects 
(in addition to the standard SMART Registry) 
Procedure/Assessment 
Enrollment visit  
(Index Visit) 
(between 1 and 21 days 
post CRT-D 
implantation 
procedure) 
12 months 
Clinic Visit 
(330 days -
390 days 
post- 
enrollment) 
Additional SOC  
Clinic Visit 
(only if per site 
SOC) 
24 months 
Clinic Visit 
(690 days -
750 days post- 
enrollment) 
36 months 
Clinic Visit 
(1050 days -
1110 days post- 
enrollment) 
Annual  
Clinic Visit 
(until last PMCF 
subject will achieve 
36 months of follow 
up) 
Informed consent process, including 
informed consent signature date 
X 
 
-- 
 
-- 
 
-- 
 
-- 
 
-- 
Inclusion/Exclusion 
X 
-- 
-- 
-- 
-- 
-- 
Demographics 
X 
-- 
-- 
-- 
-- 
-- 
Physical assessment 
X 
X 
O 
-- 
-- 
-- 
Medical history 
X 
-- 
-- 
-- 
-- 
-- 
Echo data post implant (if available) 
X 
X 
O 
-- 
-- 
-- 
NYHA Class 
X 
X 
O 
X 
X 
X 
ECG Data (if available) 
X 
X 
O 
-- 
-- 
-- 
Patient & Physician Global Assessments  
(Global Assessment Tool)  
-- 
X 
-- 
-- 
-- 
-- 
Cardiac Medications 
X 
X* 
O* 
X* 
X* 
X* 
Implanted system information 
X 
X** 
X** 
X** 
X** 
X** 
Device Initial interrogation, settings and 
status and print of Combined Report and 
Settings Report  
X 
X 
X 
X 
X 
X 
Leads measurements  
X 
X 
O 
X 
X 
X 
Optimization information as per site SOC 
X 
X 
X 
X 
X 
X 
Device Final Combined Report and 
Setting Report  
 
 
 
 
 
 
Adverse Event Assessment  
X 
X 
X 
X 
X 
X 
X = required; O = optional; -- = not required, *= Need to document changes to cardiac meds only (new, increase, decrease), ** = Need to document only if there is changes from implanted system  
NYHA = New York Heart Association; ECG = Electrocardiogram; HF = Heart Failure, SOC – Standard of Care 

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11.2. Study Candidate Screening 
After approval by the investigator’s IRB/EC and the sponsor or delegated representative the 
investigator or designee is responsible for screening potential subjects and selecting those 
who meet all inclusion criteria and do not meet any of exclusion criteria. A formal screening 
log is not required to be maintained. 
 
11.3. Informed Consent 
Subjects who meet all of the inclusion criteria, none of the exclusion criteria, and undergo the 
informed consent process, sign, and date the informed consent form are considered enrolled 
in the study. No data collection, data entry, or study specific procedure shall be performed 
prior to having appropriately consented the subject.  
11.4. Enrollment Visit - Index Visit (Day 0) 
The Enrollment Visit may occur at pre-discharge of CRT-D implantation procedure but only 
between 1 and 21 calendar days post CRT-D implantation procedure. Enrollment cannot 
occur on the same day of the implantation procedure. 
 
An overview of data to be collected at the Enrollment Visit is provided below, with further 
details followed in the sections below.   
 
 Inclusion and Exclusion (including CRT-D indication verification according BSC 
labelling) 
 Subject demographics 
 Subject Physical Assessment 
 Medical history  
 NYHA Class Assessment 
 Cardiac medications 
 Implanted system information (CRT-D IPG, RA lead, RV lead and LV lead 
information including LV lead location)  
 Device Initial Interrogation to capture current settings, programming and status 
(including battery consumption) at the beginning of the Clinic Visit 
 Lead measurements 
 BSC Optimization features data: SmartDelay test and value (if done), LV Vector 
Guide test and value (if done), LV MSP (if enabled), SmartVector and SmartOffset 
value (if done), HeartLogic information (if applicable) and other optimization 
methods as per site SOC 

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 Device Final Report to capture programming, settings, programming and status 
(including battery consumption) at the end of the Clinic Visit before subject will 
leave the site. 
 Adverse event assessment 
11.4.1. Inclusion and Exclusion Criteria 
The following values from subject’s medical record are required to demonstrate that the 
subjects meet the BSC’s labeled indication for CRT-D implantation: 
 
BSC approved labeling verification in US 
 LVEF and date of measurement (It is required that the LVEF value be measured no 
more than 6 months prior to the CRT-D implantation). 
 QRS duration 
 Bundle Branch Block morphology (LBBB or non-LBBB) 
 Heart failure etiology (ischemic or non-ischemic) 
 NYHA class 
 Cardiovascular medications 
 
BSC approved labeling in Europe 
Subjects who are at risk for sudden cardiac death caused by ventricular arrhythmias and who 
have heart failure (including asymptomatic [NYHA Class I] ischemic heart failure) with 
ventricular dyssynchrony. 
11.4.2. Subjects Demographics 
Subject’s age and sex. Race/ethnicity are only required in US. 
11.4.3. Medical History 
Subject’s history of cardiovascular diseases is required to be collected. 
11.4.4. Subject Physical Assessment 
Physical presentation will be used to provide an assessment of the subject’s condition and 
changes in clinical symptoms. Evaluation includes: 
 
Resting heart rate 
 
Height/weight 
 
12-lead ECG (if available) 
 
Presenting symptoms 
 
Blood pressure 
 
Echo post-implant data (if 
available) 

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11.4.5. NYHA Class Assessment 
The subject’s current New York Heart Association (NYHA) Class must be determined based 
on Table 11.4-1. 
Table 11.4-1: NYHA Classifications 
 
 
11.4.6. Cardiac Medications 
Subject current cardiovascular medications uses are required. For study purposes, cardiac 
medications include: diuretics, ACE inhibitors/angiotensin receptor blockers, beta blockers, 
aldosterone antagonists, Neprilysin inhibitors, Class I/III antiarrhythmics, calcium channel 
blockers, anti-hypertensive drugs, and statins. 
 
11.4.7. Implanted System Information 
The following data are required to be collected from the implanted CRT-D device, RA lead, 
RV lead, and quadripolar LV lead: 
 Manufacturer 
 Model number 
 Serial number (optional for non-BSC leads) 
 Implant date 
 Report if it was a de novo implant or a device upgrade (from pacemaker or ICD) 
 Battery consumption data: Time to explant need to be collected 
 LV Lead Location 
11.4.7.1.
The coronary venous LV lead location data are required if such information is available from 
reviewing lead imaging documents including in-procedure fluoroscopy or pre-discharge 

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chest X-rays, or can be obtained from the implanter’s dictation in the subject’s medical 
record.  
The LV lead location will be classified and recorded in eCRF as follows: 
 Anterior, anterolateral, lateral, posterolateral, or posterior  
And 
 Basal, Middle, and Apical 
11.4.8. Current Device Setting and Status 
After initial device interrogation, print a copy of the Combined Report and Settings Report to 
document current device settings and status prior to conducting any test and changing the 
programming settings. 
 
11.4.9. Battery Consumption 
The following values are required to be collected: 
 Time to explant 
 
11.4.10. 
Lead Measurements 
The following lead measurements are required for RA lead, RV lead, and LV lead: 
 Intrinsic amplitude (mV) 
 Pacing capture threshold (PCT in V/ms; the recommended pulse width is 0.4ms) 
 Pacing lead impedance ()  
 Shocking lead impedance (, RV lead) 
 Phrenic Nerve Stimulation (PNS) Threshold (V LV lead) 
The following document is required for RA lead, RV lead, and LV lead measurements: 
 Device follow-up report 
Lead measurement testing is required unless a rationale is provided. For example, the 
measurement is prohibited by a subject’s condition.  
 The pacing configurations used in the LV lead measurement testing are per the 
investigator’s discretion. It is recommended that at least one configuration must be 
tested for the LV lead, and it is recommended that it be the configuration that is 
planned for the final programming.  
The threshold should be defined as one voltage level above the level where two non-captured 
beats are observed. If multiple PCT tests were performed, only the final measurement is 
required to be entered on the eCRF. 

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11.4.11. Optimization features information 
Each site should be using Optimization features or any other method as per their site SOC. 
 
 
SmartDelay Feature Data 
11.4.11.1.
If the SmartDelay test is done per site SOC to obtain programming recommendations for the 
AV Delay and Pacing Chamber. It is per the investigator’s discretion whether to follow the 
programming recommendations.  
If SmartDelay test is done, the following values are recommended to be obtained: 
 Sensed AV delay (SAV) and Paced AV delay (PAV), both recommended and final 
programmed value (Print a copy of Settings Changes Report. This report will display 
recommended SAV, PAV and Pacing Chamber). Keep this printed report at the 
Subject File. 
 Pacing Chamber (BiV or LV Only), both recommended and final programmed 
values. 
 Rationale if the SmartDelay recommendations are not followed. 
 A sense to RV sense interval,  A sense to LV sense interval, A pace to RV sense 
interval and A pace to LV sense interval 
If the SmartDelay test is done, the following document is required: 
 Print a copy of the Settings Changes Report immediately after running the 
SmartDelay test and before any other changes in settings are made and programmed. 
This report will display the recommended changes to the SAV, PAV, and Pacing 
Chamber at pending status. 
For a step-by-step guidance on performing the SmartDelay test, see Appendix 0. 
 
 
LV VectorGuide feature Data 
11.4.11.2.
If LV VectorGuide test is done per site SOC and completed, provide the number of viable 
pacing vectors. 
Subjects must have LV and RV sensed beats for test to be successful. If the subject does not 
tolerate low rate RV pacing, stop the test and provide the rationale of not completing the test. 
The following values are recommended to be obtained when VectorGuide is performed: 
 Number of viable pacing vectors. 
 RV-LV delay (Is RV-LV test run?  If Yes, capture the values) 
 Impedance (Is Impedance test run?  If Yes, out of bounds?  Yes or No) 
 PNS (Is PNS test run? If Yes, at which tested threshold and Is PNS present) 
 Pacing Capture Threshold (Is Quick Capture test run?    

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o if Yes, capture the tested threshold and whether it is captured or not;  
o If No, Is Auto or Manual threshold test run?  If yes, capture the pacing capture 
threshold) 
If the LV VectorGuide test is done, the following document is required: 
 Print a copy of the VectorGuide Report 
For a step-by-step guidance on performing the LV VectorGuide test, see Appendix 26.2. 
 
 
LV MSP feature Data 
11.4.11.3.
For subjects with LV MSP feature enabled, it is required to use VectorGuide to assess viable 
LV pacing vectors from all tested pacing vectors. It is recommended to use the pacing 
vectors recommended by SmartVector test; however, final selection of the pacing vectors is 
per investigator’s discretion.  
The following values are required for subjects with LV MSP enabled: 
o RV-LV delay value for all 4 electrodes as cathode: E1-Tip1, E2-Ring2, E3-
Ring3, E4-Ring4 
 LV pacing impedance for all tested vectors 
 Phrenic Nerve Stimulation (PNS) test results for all tested vectors 
 LV Quick Capture threshold test 
 Number of viable pacing vectors 
 
For subjects with LV MSP feature enabled, the LV pacing vectors will be recommended by 
the required SmartVector test; however, since it is not required to follow the recommendation 
from SmartVector, final pacing configurations for PCT measurement are per the 
investigator’s discretion. 
Investigator rationale is required commended if investigator not following LV MSP final 
pacing configuration feature recommendations. 
 
MSP SmartVector Test (only for subjects with MSP turned on) 
 LVa and LVb, both the recommended and final programmed values. 
 Rationale if the LVa and LVb recommendations are not followed. 
For a step-by-step guidance on performing SmartVector operation, see Appendix 26.3 
 
MSP SmartOffset Test (only for subjects with MSP turned on) 
 SmartOffset values, both the recommended and final programmed values. 
 Rationale if the SmartOffset recommendations are not followed. 
For a step-by-step guidance on performing SmartOffset operation, see Appendix 26.4 

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 
Device features used report (if applicable) 
 
Device Combined Report (at the beginning and at 
the end of the visit) 
 
11.5. 12 months Clinic Visit 
 
The 12 months Clinic Visit is must be performed at 330-390 calendar days post Enrollment 
Visit (Required)  
 
Subjects with LATITUDE remote monitoring system may have their device performance and 
diagnostic data downloaded remotely from the LATITUDE BSC team during these visits 
timeframe. The device data transmission via LATITUDE will not be replacing the Clinic 
Visit. 
An overview of data to be collected at 12 months Clinic Visit is provided below, with further 
details followed in the sections below:  
 
 Subject Physical Assessment 
 Cardiac Medication Changes 
 NYHA class assessment 
 Patient Global Assessment (PGA) 
 Physician Global Assessment (PhGA) 
 HF hospitalization information 
 Device Initial Interrogation to capture current settings, programming and status 
(including battery consumption) at the beginning of the Clinic Visit 
 Changes in programming or features since the last  Clinic Visit  
 Lead measurements 
 BSC Optimization features data: SmartDelay test and value (if done), LV Vector 
Guide test and value (if done), LV MSP (if enabled), SmartVector and SmartOffset 
value (if done), HeartLogic information (if applicable) and other optimization 
methods as per site SOC 
 Final device programming, settings and status (including battery consumption) at the 
end of the Clinic Visit before subject will leave the site. 
 Adverse Events Assessment 
 

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11.5.1. Subject Physical assessment 
Physical presentation will be used to provide an assessment of the subject’s condition and 
changes in clinical symptoms following instructions from Section 11.4.4. 
11.5.2. Cardiac Medication Changes 
Subject current cardiovascular medications changes only from their last study visit (increase, 
decrease, new or removed). Medications collected include: diuretics, ACE 
inhibitors/angiotensin receptor blockers, beta blockers, aldosterone antagonists, Neprilysin 
inhibitors, Class I/III antiarrhythmics, calcium channel blockers, anti-hypertensive drugs, and 
statins. 
11.5.3. NYHA Class Assessment 
The subject’s current NYHA Class must be determined based on Table 11.4-1. 
11.5.4. Physician Global Assessment 
The current Physician Global Assessment (PhGA) will be filled out by the 
investigator/delegated site staff based on the evaluation of the subject’s status from multiple 
clinical aspects. A comparison of the assessment tool for the PGA and PhGA is shown in 
Table 11.5-1: Global Assessment Tool: Physician Global Assessment (PhGA) and 
Patient Global Assessment (PGA)Table 11.5-1Error! Reference source not found.. 
11.5.5. Patient Global Assessment 
The current PGA must be filled out by the subject, as specified in the Assessment Tool in 
Table 11.5-1Error! Reference source not found.. 
 
Table 11.5-1: Global Assessment Tool: Physician Global Assessment (PhGA) and 
Patient Global Assessment (PGA) 
Physician Global Assessment (PhGA) 
Patient Global Assessment (PGA) 
How is the patient’s clinical status today 
compared to his or her status at the time of 
baseline? 
 
Markedly improved 
 
Moderately improved 
 
Mildly improved 
 
No change 
 
Mildly worse 
 
Moderately worse 
 
Markedly worse 
How do you feel today compared to how you felt 
when you started the study?                                      
 
Very much better 
 
Much better 
 
A little better 
 
No change 
 
A little worse 
 
Much worse 
 
Very much worse 

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11.5.6. Definition and Components of the Clinical Composite Score 
The Clinical Composite Score (CCS) will be calculated for all subjects at the 12 Month Visit. 
The CCS consists of the following components: 
 
 All-cause mortality 
 Heart Failure (HF) hospitalization 
 Patient Global Assessment (PGA) 
 NYHA class 
 
 HF Hospitalization Definition 
11.5.6.1.
For the purpose of the CCS calculation, HF hospitalization is defined as an HF event with a 
primary cause of HF and either of the conditions below is met: 
 
 Subject is admitted and discharged with a calendar date change. 
 Subject is not hospitalized but received one or more IV medications including 
diuretics, inotropes, vasodilators, other parenteral therapy, or aquapheresis 
 PGA Classification 
11.5.6.2.
Interpretation of no change status in PGA is defined as the following: 
 A little better, no change, and a little worse. 
A little better and a little worse are considered placebo effect and are treated as no change in 
PGA status. See for a detailed description of the PGA assessment tool Table 11.5-1 
 
 CCS Status Classification 
11.5.6.3.
Subjects will be classified as improved, unchanged, or worsened by comparing their clinical 
response in the current visit to their enrollment visit. At the 12 months Clinic Visit, subjects’ 
status will be compared to their status at enrollment. The following criteria will be used: 
 
 Improved: Subjects are considered improved if they experienced a favorable change 
in at least one NYHA functional class or in the PGA (or both) while remaining alive and free 
of HF hospitalization comparing to their status in the Enrollment Visit. See Table 11.5-1 on 
selecting improved PGA status. 
  
 Worsened: Subjects are considered worsened if any of the followings occurs: 
o died (from any cause) or 
o experienced an HF hospitalization or 
o reported worsening of at least one NYHA functional class or 
o reported worsening of the PGA comparing to their status immediately prior to 
receiving the CRT-D implantation. See Table 11.5-1 on selecting worsened 
PGA status. 

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 Unchanged: Subjects are considered unchanged if they are neither improved nor 
worsened. 
11.5.7. Current Device Settings and Status 
After initial device interrogation, print a copy of the Combined Report and Settings Report to 
document current device settings and status prior to conducting any test and changing the 
programming settings. 
 
11.5.8. Changes in programming since the last Clinic Visit 
 Collect changes done in programming since the last Clinic Visit: 
 Parameters modified and Features enabled/disabled  
 Who made the change (investigator, device check facility, emergency services, other) 
 Date of the change  
 Impact of the change.  
 
11.5.9. SmartDelay test and value 
If SmartDelay test done please follow instructions from Section 11.4.11.1 
11.5.10. LV VectorGuide test and value  
If LV Vector Guide test done, please follow instructions from Section 11.4.11.2 
11.5.11. SmartVector and SmartOffset value 
If SmartVector and Smart Offset tests done, please follow instructions from Section 
11.4.11.3 
11.5.12. Current device setting and status 
Print a copy of the Quick Notes Report to document current device settings and status prior 
to conducting any test and changing the programming settings. A list of settings and status, 
including but not limited to the SmartDelay, Vector Guide, LV MSP and HeartLogic  
settings, percent of pacing (% RV pacing, %LV pacing), and percent of AT/AF are 
recommended to be collected (if applicable). 
11.5.13. Battery Consumption 
The following values are required to be collected: 
 Time to explant 

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An overview of data to be collected at 24, 36 months Clinic Visit and Annual Visit is 
provided below, with further details followed in the sections below.   
 NYHA class assessment 
 Cardiac Medications Changes 
 Current device setting and status 
 Lead measurements 
 LV MSP feature use and programming (if applicable) 
 HeartLogic feature data (if applicable) 
 Battery consumption 
 Final device settings and status 
 Adverse Events Assessment 
 
11.7.1. NYHA Class Assessment 
The subject’s current NYHA Class must be determined based on Table 11.4-1. 
 
11.7.2. Cardiac Medication Changes 
Subject current cardiovascular medications changes from their last study visit (increase, 
decrease, new or removed). Medications collected include: diuretics, ACE 
inhibitors/angiotensin receptor blockers, beta blockers, aldosterone antagonists, Neprilysin 
inhibitors, Class I/III antiarrhythmics, calcium channel blockers, anti-hypertensive drugs, and 
statins. 
 
11.7.3. Current device setting and status 
After initial device interrogation, print a copy of the Combined Report and Settings Report to 
document current device settings and status prior to conducting any test and changing the 
programming settings. 
 
11.7.4. Changes in programming since the last Study Clinic Visit 
 Collect changes done in programming since the last Clinic Visit  
 Parameters modified and Features enabled/disabled  
 Who made the change (investigator, device check facility, emergency services, other) 
 Date of the change  
 Impact of the change 
 

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end of the visit) 
 
Device features used report (if applicable) 
 
Device Combined Report (at the beginning and at 
the end of the visit) 
 
11.8. Study Completion 
Subjects enrolled in SMART Registry only will conclude study participation once the 12 
months visit will be performed. However all subjects enrolled also in NG4 PMCF Cohort 
will complete study participation only when the last enrolled subject in the PMCF will have 
completed the 36 months Clinic Visit. Sites will continue to follow subjects until notified of 
follow-up completion. Sites will be notified when subject follow-up at their site is complete 
for the study.    
12. Statistical Considerations 
12.1. Endpoints 
12.1.1. Primary Endpoint 
CRT Response rates will be determined in the entire SMART Registry and in selected 
subgroups. No formal hypotheses will be evaluated for this analysis. To fulfill post-approval 
requirements related to the NG4 family of devices, the NG4 PG-related complication free 
rate (CFR) at 36 months will be evaluated in the subjects included in the NG4 PMCF Cohort.  
Details of the SMART Registry Primary Objective and the NG4 PMCF Cohort Primary 
Endpoint are provided in the following sections. 
12.1.2. SMART Registry Primary Endpoint 
 Hypotheses 
12.1.2.1.
There are no formal hypotheses to be tested for the SMART Registry Primary Objective. 
 Sample Size  
12.1.2.2.
Due to a lack of hypotheses for this objective, the sample size cannot be determined through 
traditional statistical powering techniques.  It is, however, desired to have a high degree of 
confidence in the CRT Response rates obtained in the study.  In order to obtain a two-sided 
95% confidence interval width of the overall SMART Registry CRT Response rate that does 
not exceed 5%, a total of 2000 subject enrollments are required.  Additionally, it is expected 
that with a total of 2000 enrollments, each subgroup analysis will include a sufficient sample 
of approximately 50 subjects. 
 Statistical Methods 
12.1.2.3.
The Clinical Composite Score allows for three levels of CRT Response: Improved, 
Unchanged or Worsened. The number and percent of SMART Registry subjects contributing 
to each level of CRT Response will be calculated. 

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CRT Response rates will be compared between selected subgroups. Due to the ordinal nature 
of the three CRT response levels defined by the Clinical Composite Score, statistical tests 
accounting for ordinality of response will be used, when appropriate.  In analyses comparing 
two subgroups, a Cochran-Armitage test for trend will be employed.  If more than two 
subgroups will be compared, a cumulative logit model or some other appropriate test will be 
used.  
12.1.3. NG4 PMCF Endpoint 
 Hypotheses 
12.1.3.1.
The NG4 PMCF Primary Endpoint was designed to evaluate the safety of the NG4 device 
when LV MSP is enabled.  In the subjects included in the NG4 PMCF Cohort, the NG4 PG-
related complication free rate (CFR) at 36 months will be used to evaluate the PMCF 
Primary Endpoint.   
A PG-related Complication will be defined as those detectable adverse events that resulted 
in:  
 Death 
 Serious injury 
 Correction of PG failure requiring invasive intervention 
 Permanent loss of PG device function. Permanent loss of device function is defined as 
any Pulse Generator (PG) that reverts to Safety Core or any PG rendered unable to 
deliver pacing or shocks 
Complications that are determined to be associated with the PG will be considered PG-
related complications (PG) and count against the PMCF endpoint.  Complications related to 
the LV, RV, RA leads will not be counted against the PMCF endpoint. 
 Hypotheses 
12.1.3.2.
The following hypotheses will be evaluated to evaluate the safety of the NG4 device: 
H0:  PG-related CFR at 36 months ≤ 88.5% 
HA:  PG-related CFR at 36 months > 88.5% 
To ensure that the safety of the NG4 devices with LV MSP enabled is acceptable, the 
performance goal for this endpoint was based on the observed safety of prior approved 
Boston Scientific devices in the following studies: CAPTIVATE, LSS of 4-SITE, MADIT 
CRT, MultiSENSE, NAVIGATE X4. Prior devices in these studies have shown a PG-related 
complication-free rate of 98.5% through 36 months of follow-up. The performance goal of 
88.5% was derived from the prior performance of 98.5% minus 10% to account for 
variability in the estimate. Expected performance of the NG4 device was based on the 
observed rate of prior devices. 

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 Sample Size  
12.1.3.3.
A minimum of 63 subjects are required to sufficiently power the NG4 PMCF Primary 
Endpoint. An additional requirement is follow-up of a minimum of 60 subjects with usage of 
the LV MSP feature. Therefore, follow-up of 63 subjects with LV MSP enabled will satisfy 
both requirements. To account for the expected 15% annual attrition, a minimum of 103 
subjects with LV MSP usage will be followed to achieve 63 subjects at 36 months. A 
minimum of the first 103 subjects identified with LV MSP usage will be included in the NG4 
PMCF Cohort.  
 Statistical Methods 
12.1.3.4.
The Primary Endpoint will be calculated using Kaplan-Meier methodology.  The 95% one-
sided pointwise log-log confidence limit of the PG-related complication-free rate at 36 
months will be compared to the performance goal of 88.5%.  If the lower confidence limit 
exceeds 88.5%, the null hypothesis will be rejected. 
 
12.2. General Statistical Methods 
12.2.1. Analysis Sets 
All subjects with complete Clinical Composite Score data at 12 months will contribute to the 
analyses evaluating CRT Response rates.  All subjects in the NG4 PMCF Cohort will 
contribute data to the PMCF Primary Endpoint. 
12.2.2. Control of Systematic Error/Bias 
Several subgroups, multivariate and other analyses are planned to evaluate the primary 
objective of the SMART Registry.  No adjustments to the significance level (i.e., alpha) due 
to these multiple tests will be made.  Rather, interpretation of all results will consider the 
biological plausibility of the findings as well as the consistency with other results obtained in 
this study and from other external sources.  
The type I error rate for the PMCF Primary Endpoint will be contained at 5% by use of a 
one-sided 5% alpha in the analysis.   
12.2.3. Number of Subjects per Investigative Site 
Sites will be allowed to enroll a maximum of 200 subjects, equal to 10% of the SMART 
Registry expected enrollment. 
12.3. Data Analyses 
12.3.1. Other Endpoints/Measurements  
Additional analyses may be performed to assist in the evaluation of the Primary Objective: 

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 CRT Response in the overall cohort and in subgroups using groupings of the three 
levels of the Clinical Composite Score:  
o Improved vs. Unchanged/Worsened 
o Improved/Unchanged vs. Worsened 
 Evaluation of the components of the Clinical Composite Score in the overall cohort 
and in subgroups: 
o All-cause mortality 
o Heart failure events 
o NYHA Class 
o Quality of life (patient Global Assessment instrument) 
Utilization patterns of device features and diagnostics will also be calculated, if available: 
 MultiSite Pacing (MSP) 
o Number and percent of subjects with MSP usage overall and throughout 
follow-up 
o Physician rationale for utilizing MSP 
o Programming parameters (i.e., vectors) associated with MSP usage 
 HeartLogic use (if available) 
o Number and percent of subjects with HeartLogic usage overall and throughout 
follow-up 
o Physician rationale for utilizing HeartLogic 
o Physician response to HeartLogic alerts 
 SmartDelay 
o Number and percent of subjects with SmartDelay usage  
 Vector Guide 
o Number and percent of subjects with Vector Guide usage  
 Programming of pacing vectors 
o Rationale for selection of pacing vector (e.g., lowest pacing capture threshold 
without extracardiac stimulation, longest RV-LV delay, etc.) 
12.3.2. Interim Analyses  
No formal interim analyses are planned for stopping for superiority or futility.  Interim 
analyses may be performed to support publications. Analysis of each endpoint will be 
performed when all applicable data for that endpoint has been collected. 

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12.3.3. Subgroup Analyses 
The list of baseline covariates (with applicable subgroups in parentheses) includes, but is not 
necessarily limited to: 
 
 Ischemic Etiology (Ischemic vs Non-Ischemic) 
 Bundle Branch Block morphology (LBBB vs Non-LBBB) 
 NYHA class (I/II vs III/IV) 
 Presence of atrial fibrillation (Yes or No ) 
 Diabetes (Yes vs. No) 
 Sex (Male vs. Female) 
 Age < 65 years vs. ≥ 65 years 
 RV-LV electrical delay (< 70 ms vs. ≥ 70 ms) 
 QRS-LV at the implantation site 
 QRS width (< 150 ms vs. ≥ 150 ms) 
 
CRT Response rates (Full Registry) and PG-related complication-free rates (NG PMCF 
Cohort) will be compared between the two subgroups for each covariate. A Cochran-
Armitage test for trend will be performed to compare CRT Response rates across subgroups. 
A log-rank test will be used to compare PG-related complication-free rates across subgroups. 
Additional cutpoints may be evaluated for continuous covariates, based on the data and/or 
clinical determination. 
12.3.4. Justification of Pooling 
The poolability of data by center will be tested among the NG4 PMCF Cohort. This analysis 
will be performed to determine whether there are NG4 PMCF endopoint differences from 
center-to-center. 
 
Center-to-center heterogeneity will be assessed by performing random effects logistic 
regression analysis. 
 
Participating center will be added into the model as a random effect. Centers will be 
deemed to be heterogeneous if the variance of the random center effect is found to 
significantly differ from zero. A significance level of 15% will be used for each test. 
12.3.5. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in a Statistical Analysis Plan approved prior to performing the analyses. 
 
Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason for the deviation. 

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13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by EDC System. All changes 
made to the clinical data will be captured in an electronic audit trail and available for review 
by the sponsor or its representative. The associated RAVE software and database have been 
designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system and will 
be issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database.  
13.2. Data Retention 
The Principal Investigator or his/her designee or participating site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study subjects in compliance with ICH/GCP guidelines.  Documents 
must be retained for at least 2 years after the last approval of a marketing application or until 
at least 2 years have elapsed since the formal discontinuation of the registry. These 
documents will be retained for a longer period of time by agreement with BSC or in 
compliance with other country/regional/local regulations.  
The Principal Investigator or his/her designee will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Principal Investigator or his/her designee withdraws responsibility for maintaining these 
essential documents, custody must be transferred to an individual who will assume 
responsibility and BSC must receive written notification of this custodial change. Sites are 
required to inform Boston Scientific in writing where paper or electronic files are maintained 
in case files are stored off site and are not readily available. 
14. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 

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15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC of any deviation from the protocol to protect the life or 
physical well-being of a subject in an emergency, and those deviations which affect the 
scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days.  
All deviations from the protocol, with the reason for the deviation and the date of occurrence, 
must be documented and reported to the sponsor using EDC. Sites may also be required to 
report deviations to the IRB/EC, per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
16. Compliance 
16.1. Statement of Compliance 
This study will be conducted in accordance post market clinical follow up guidelines and will 
follow the applicable sections of ISO 14155(Clinical Investigation of Medical Devices for 
Human Subjects – Good Clinical Practice), the relevant parts of the ICH Guidelines for Good 
Clinical Practices, ethical principles that have their origins in the Declaration of Helsinki, and 
pertinent individual country laws and regulations. The study shall not begin until the required 
approval/favorable opinion from the IRB/EC and/or regulatory authority has been obtained, 
if appropriate. Any additional requirements imposed by the IRB/EC or regulatory authority 
shall be followed, if appropriate.  
 
16.2. Investigator Responsibilities 
The Principal Investigator of an participating site is responsible for ensuring that the study is 
conducted in accordance with the Clinical Study Agreement, the clinical investigation plan/, 
ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
 Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
 Prior to beginning the study, sign the Protocol Signature page documenting his/her 
agreement to conduct the study in accordance with the protocol. 

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 Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
 Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
 Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
 Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
 Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
 Report to sponsor, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
 Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE, if required by the national 
regulations or this protocol or by the IRB/EC, and supply BSC with any additional 
requested information related to the safety reporting of a particular event. 
 Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
 Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
 Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC requirements. 
 Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
 Inform the subject of the nature and possible cause of any adverse events experienced. 
 As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
 Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
 Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 

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treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
 Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
 Ensure that, if appropriate, subjects enrolled in the registry are provided with some means 
of showing their participation in the clinical investigation, together with identification 
and compliance information for concomitant treatment measures (contact address and 
telephone numbers shall be provided). 
 Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
 Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from registry while fully respecting the subject’s rights. 
 Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the registry. 
 Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the registry is appropriately performed and documented, where applicable. 
16.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of the clinical study.  
16.3. Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the participating site will provide to the sponsor 
documentation verifying that their IRB/EC is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory 
requirements.   
A copy of the written IRB/EC and/or competent authority approval of the protocol (or 
permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the study. Prior approval must also be obtained 
for other materials related to subject recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by local/country or IRB/EC requirements. Copies of the Investigator’s reports 
and the IRB/EC continuance of approval must be provided to the sponsor.  
16.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 

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representative including, but not limited to Contract Research Organization (CRO) will have 
access to these confidential records. Authorized regulatory personnel have the right to inspect 
and copy all records pertinent to this study. Study data collected during this study may be 
used by BSC for the purposes of this study, publication, and to support future research and/or 
other business purposes. All data used in the analysis and reporting of this study will be 
without identifiable reference to specific subject name. 
Boston Scientific will keep subjects’ identifiable health information confidential in 
accordance with all applicable laws and regulations.  Boston Scientific may use subjects’ 
health information to conduct this research, as well as for additional purposes, such as 
overseeing and improving the performance of its device, new medical research and proposals 
for developing new medical products or procedures, and other business purposes. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1. Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol, 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices (including 
programmers, analyzers, and other support equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during implant or follow-up, assist with the conduct of testing 
specified in the protocol, and interact with the subject to accomplish requested activities. 
Typical tasks may include the following. 
 Interrogating the device or programming device parameters to investigator-requested 
settings as well as operating equipment 
 Performing lead diagnostic testing using a Pacing System Analyzer or programmer to 
obtain pacing and sensing thresholds and impedance measurements 
 Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
 Assisting with the collection of study data from Pacing System Analyzers, programmers, 
and other equipment 
 Entering technical data on technical source form as long as the responsible investigator 
verifies and signs the completed worksheet  
 Print out programming reports directly from the clinician programmer and provide 
original to clinical site as source documentation 
 Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the subject.  
 

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In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
 Observing testing or medical procedures to provide information relevant to protocol 
compliance 
 Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
 Practice medicine 
 Provide medical diagnosis or treatment to subjects 
 Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the investigator 
 Independently collect critical study data (defined as primary or secondary endpoint data) 
 Enter data in electronic data capture systems or on paper case report forms 
 
16.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
17. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
 
18. Potential Risks and Benefits 
18.1. Anticipated Adverse Events  
 
The following anticipated adverse events (AE) for the SMART Registry subjects are the 
same as any other subject implanted with a CRT-D system and not participating in any study. 

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Subjects may develop psychological intolerance to a pulse generator system and may 
experience the following: 
 Dependency 
 Depression 
 Fear of premature battery depletion  
 Fear of shocking while conscious 
 Fear that shocking capability may be lost 
 Imagined shocking  
 Fear of device malfunction  
18.2. Anticipated Adverse Device Effects  
Adverse Device Effects that are part of the listing in the previous18.1 section are to be 
considered Anticipated Device Effects. 
18.3. Risks Associated with the Study Device(s)  
There are no additional risks associated with the study devices that are above those of BSC 
commercially approved and market available CRT-D devices. 
18.4. Risks associated with Participation in the Clinical Study 
There are no additional risks that are associated with participation to the present study 
beyond those listed above, and all the visits associated to this protocol are performed as part 
of standard clinical practice. 
18.5. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
18.6. Anticipated Benefits 
There may be no benefit to the subject. However, medical science and future subjects may 
benefit from their participation in this registry. 
18.7. Risk to Benefit Rationale 
The implantable CRT-D systems and accessories used for this Registry will be commercially 
available and are considered to be SOC for subjects indicated for such implants. The risks 

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involved with subject participation in this study are essentially the same as those for subjects 
not participating in the study. 
19. Safety Reporting 
 
19.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
 All Serious Adverse Events 
 All Adverse Device Effects 
o Events listed in the arrhythmia logbook, should be reported only if determined 
to be clinically significant by the investigator and/or delegated site staff (i.e. 
ATR, PMT, etc.) 
o Any new onset/diagnosis of VT/VF requiring anti-arrhythmic therapy, or per 
the PI, clinically worsening VT/VF requiring Therapy. (Appropriate VT 
therapy that is not considered clinically worsening per the PI is not to be 
reported). 
 All Device Deficiencies  
 Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
 All Heart Failure (HF) and All Cardiac related adverse events requiring IV or 
invasive therapy, including new onset cardiac events, or worsening in severity or 
frequency of pre-existing conditions. 
An adverse event is deemed as a HF Event if the primary cause is HF and either of 
following conditions is met: 
o In-patient hospitalization ≥ 24 hours 
o No hospitalization but received one or more IV medications including 
diuretics, inotropes, vasodilators, other parenteral therapy, or aquapheresis. 
Adverse event collection begins after the subject signs the informed consent. Events which 
occur prior to the signing of the informed consent form, and per the investigator/delegated 
site staff are a result of the device implant procedure should not be reported. Even if such 
event requires a treatment that is executed after the informed consent is signed. (e.g. 
hematoma that requires intervention is not an adverse event as long as it does not worsen 
after consenting; infection at the incision site is not an adverse event as long as it does not 
worsen after consenting; planned medical procedure or lead revisions are not adverse events 
as long as the event is identified prior to the consent). These are considered preexisting 
conditions and are not reportable. If the event worsens after consenting and meets criteria for 
a reportable event then they must be reported (e.g. hematoma that is worsened and requires 
intervention; a new infection at the incision site or an infection that is worsened and requires 

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intervention). If the study subject is consented while still hospitalized from the initial device 
implant, and an event occurs which meets the definition of an SAE, the event must be 
reported. 
The medical diagnosis should be reported for reported events. In case the diagnosis is not 
available, individual symptoms can be reported to fulfill reporting timelines. If a diagnosis 
becomes available at a later date, it should be added to the reported event. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any AE required by the protocol, experienced by the study subject after informed consent 
and once considered enrolled in the study (as defined in study subject classification section), 
whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation. Death should not be reported as an SAE, but 
should be reported as an outcome of an SAE and only one SAE should have the outcome 
documented as fatal (see Table 19.2-1 for AE definitions). 
Refer to Section 18.3 for the known risks associated with the study device(s). 
 
19.2. Definitions and Classification 
Adverse event definitions are provided in Table 19.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155and MEDDEV 2.7/3 for clarification 
purposes. Reportable events are defined in Table 19.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155and MEDDEV 2.7/3 for clarification 
purposes. 
 
Table 19.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the investigational 
medical device.  
NOTE 1: This includes events related to the investigational medical device 
or comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of  
ISO 14155  and  MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to  serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare 
of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in the 
risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
A inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
NOTE: The following section is only applicable to RM. 
 
Clinical Observation 
Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
A clinical observation is a clinical event that did not result in invasive 
intervention, injury, or death, and is not an unanticipated adverse event.  
Corrective actions were simple adjustments such as reprogramming of the 
pulse generator or antibiotic treatment of a pocket infection 
Clinical Complication 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
A clinical complication is a clinical event that required an invasive 
intervention, injury, or death (e.g., surgical evacuation of a hematoma, lead 
dislodgment requiring lead repositioning, generator replacement, loss or 
abandonment of therapy). 
Type I 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
Related to the investigational device or therapies.  
 
Type II 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
Related to protocol or procedures.  Specifically related to protocol testing 
that is not patient standard of care.     
Type III 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
Not related to the investigational device(s), system component(s), or 
labeling, but would not have occurred in the absence of the investigational 
device(s) and/or system component(s).  This includes clinical events related 
to commercially released devices that are used in conjunction with 
investigational device(s) or protocol procedures. 
Type IV 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Related to a change in patient’s condition. 

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Table 19.2-1: Safety Definitions 
Term 
Definition 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
Type V 
 Ref: FDA Guidance for the 
Submission of 
Research and Marketing 
Applications for Permanent 
Pacemaker Leads and for 
Pacemaker Lead Adaptor 
510(k) Submissions 
Comments Only.  On occasion, comments were inadvertently entered in the 
adverse event text field of the case report form (CRF). Comments identified 
by the CRF reviewer were assigned a Type V code and not included in this 
report. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
 
19.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device or procedure. See 
criteria in Table 19.3-1:  
 

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Table 19.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or 
the procedures; 
- the serious event does not follow a known response pattern to the medical device (if 
the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the device 
or procedure; the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment or 
other risk factors); 
- the event does not depend on a false result given by the investigational device used 
for diagnosis, when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
The relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained. 
Possibly Related 
The relationship with the use of the investigational device is weak but cannot be ruled 
out completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases 
were relatedness cannot be assessed or no information has been obtained should also 
be classified as possible. 
Probably Related 
The relationship with the use of the investigational device seems relevant and/or the 
event cannot reasonably explained by another cause, but additional information may 
be obtained. 
Causal Relationship 
The serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
- the event has a temporal relationship with investigational device use/application or 
procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled out; 

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Table 19.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational device used for 
diagnosis, when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious event. 
 
19.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 19.4-1. 
Adverse events must always be reported through the EDC system for SMART Registry. 
However, in the case of any issues where alternative method of reporting is necessary (i.e. 
the EDC system is not available), please report the adverse event to Boston Scientific by 
sending the Event Notification Form via email to the following email address: 
SmartRegistry.Safety@bsci.com 
 
Table 19.4-1: Investigator Reporting Requirements  
Event Classification 
Communication Method  
Communication Timeline post-market 
studies**  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE eCRF page with 
all available new and updated 
information.  
 
d) Within 1 business day of first becoming 
aware of the event. 
e) Terminating at the end of the study 
Serious Adverse Event  
Complete AE eCRF page with 
all available new and updated 
information. 
f) Within 10 business days after becoming 
aware of the event or as per 
local/regional regulations.  
g) Reporting required through the end of 
study 
Provide all relevant source 
documentation (unidentified) 
for reported event upon 
request of the sponsor 
h) When documentation is available 
Serious Adverse Device 
Effects 
Complete AE eCRF page with 
all available new and updated 
information. 
i) Within 2 business days of first 
becoming aware of the event or as per 
local/regional regulations. 
j) Reporting required through the end of 

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Table 19.4-1: Investigator Reporting Requirements  
Event Classification 
Communication Method  
Communication Timeline post-market 
studies**  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
the study 
Provide all relevant source 
documentation (unidentified) 
for reported event 
k) When documentation is available 
Device Deficiencies 
(including but not limited to 
failures, malfunctions, and 
product nonconformities) 
Note:  Any Investigational 
Device Deficiency that might 
have led to a serious adverse 
event if a) suitable action had 
not been taken or b) 
intervention had not been 
made or c) if circumstances 
had been less fortunate is 
considered a reportable event. 
 
Complete Device Deficiency 
eCRF with all available new 
and updated information.  
l) Within 2 business days of first 
becoming aware of the event. Reporting 
required through the end of the study 
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness and 
relationship to the device.  
m) 
In a timely manner  (e.g. 
recommend within 30 business days) after 
becoming aware of the information 
n) Reporting required through the end of 
study 
Abbreviations: AE=adverse event; CRF=case report form; IDE=Investigational Device Exemption; 
UADE=unanticipated adverse device effect 
 
19.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer) 
will be documented and reported to BSC. If possible, the device(s) should be returned to 
BSC for analysis. Device failures and malfunctions should also be documented in the 
subject’s medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, an adverse event that results from a 
device failure or malfunction would be recorded as an adverse event on the appropriate 
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Any Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
19.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators and regulatory authorities, as applicable. The Principal Investigator is 
responsible for informing the IRB/EC, and regulatory authorities of UADE and SAE as 
required by local/regional regulations.. 
19.7. Subject Death Reporting 
A subject death during the study must be reported to Boston Scientific as soon as possible 
and, in any event, within three (3) calendar days of center. The center’s IRB/EC must be 
notified of any deaths in accordance with that center’s IRB/EC policies and procedures. 
Whenever possible, the device should be interrogated and BSC system components (e.g., the 
device) should be removed intact and returned promptly to BSC RM for analysis.  
A detailed narrative (death letter) that provides detailed information describing the 
circumstances surrounding the death is required. A death narrative in the local language is 
acceptable, if accompanied by a translation in English. The details listed below should be 
addressed in the death narrative, in order for BSC to understand the circumstance 
surrounding the death:   
 Date and time of death; 
 Place death occurred; 
 Immediate cause of death; 
 Rhythm at the time of death, if known (include any available documentation); 
 Whether or not the death was witnessed; 
 Whether the subject had worsening heart failure; 
 Any other circumstances surrounding the death; 
 Approximate time interval from the initiating event to death (temporal course) – items 
to consider include, but are not limited to: information regarding last time subject was 
seen by investigator, last office visit, etc. 
 Investigator or co-Investigator signature and date. 
Whenever possible, the CRT-D device is recommended be interrogated. Other Source 
documents maybe requested at BSC. BSC Medical Safety representatives must review 
information regarding subject deaths.  
20. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to any study-required procedures and/or 
testing, or data collection.  

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The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority body, as applicable. The ICF must be 
accepted by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC, or central 
IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC.  Any modification requires acceptance from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the site in obtaining a written consent translation. Translated consent forms must 
also have IRB/EC approval prior to their use.  Privacy language shall be included in the body 
of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
 be conducted by the Principal Investigator or designee authorized to conduct the process,  
 include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
 avoid any coercion of or undue influence of subjects to participate, 
 not waive or appear to waive subject’s legal rights, 
 use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
 provide ample time for the subject to consider participation and ask questions if 
necessary, 
 ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning 
of such an event). Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 

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study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be re-
consented. 
21. Committees 
21.1. Safety Monitoring Process 
To promote early detection of safety issues, the BSC Safety Trials Operations group will 
provide the initial evaluations of safety events to the BSC Medical Safety group. The BSC 
Medical Safety Group includes physicians with knowledge in the necessary therapeutic and 
subject matter expertise to evaluate and classify the events into the categories outlined above. 
During regularly scheduled monitoring activities, clinical research monitors will support the 
dynamic reporting process through their review of source document and other data 
information.  
 
21.2. Steering  Committee 
The Steering Committee is independent of Boston Scientific and is responsible for the overall 
conduct of the study with regard to protocol development, study progress, subject safety, and 
overall data quality and integrity.  
 
22. Suspension or Termination 
22.1 Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or administrative reasons and reasons 
related to protection of subjects.  Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of study termination. 
22.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
 The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
 An enrollment rate far below expectation that prejudices the conclusion of the study.  

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 A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 
22.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval 
Any investigator, or IRB/ EC in the SMART Registry may discontinue participation in the 
study or withdrawal approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
22.3 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and to 
Boston Scientific, unless this action would jeopardize the rights, safety, or welfare of the 
subjects. 
22.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific Corporation reserves the right to stop the inclusion of subjects at a study 
site at any time after the study initiation visit if no subjects have been enrolled  for a period 
beyond 6 months after site initiation, or if the site has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of site participation, the IRB/EC and regulatory authorities, as 
applicable, will be notified. All subjects enrolled in the study at the site will continue to be 
followed as per standard of care. The Principal Investigator at the site must make provision 
for these follow-up visits unless BSC notifies the participating site otherwise. 
23. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 

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of the study. Boston Scientific Corporation adheres to the Contributorship Criteria set forth in 
the Uniform Requirements of the International Committee of Medical Journal Editors 
(ICMJE; http://www.icmje.org). In order to ensure the public disclosure of study results in a 
timely manner, while maintaining an unbiased presentation of study outcomes, BSC 
personnel may assist authors and investigators in publication preparation provided the 
following guidelines are followed. 
 All authorship and contributorship requirements as described above must be followed. 
 BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
 The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission. 
24. Reimbursement and Compensation for Subjects 
24.1. Subject Reimbursement 
Travel and other expenses incurred by subjects as a result of participation in the study will be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations.   
 
24.2. Compensation for Subject’s Health Injury 
Boston Scientific Corporation will purchase an insurance policy to cover the cost of potential 
health injury for study subjects, and if required by applicable law.  
25. Bibliography 
1. Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization therapy for the 
treatment of heart failure in patients with intraventricular conduction delay and 
malignant ventricular tachyarrhythmias. J Am Coll Cardiol 2003; 42(8):1454-9. 
2. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or 
without an implantable defibrillator in advanced chronic heart failure.  New Engl J 
Med 2004; 350(21):2140-50. 
3. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the 
prevention of heart-failure events. N Engl J Med 2009;361(14):1329-38. 
4. Packer M: Proposal for a new clinical end point to evaluate the efficacy of drugs and 
devices in the treatment of chronic heart failure. J Card Fail 2001;7(2):176-82. 
5. Delgado V, van Bommel RJ, Bertini M, et al. Relative merits of left ventricular 
dyssynchrony, left ventricular lead position, and myocardial scar to predict long-term 
survival of ischemic heart failure patients undergoing cardiac resynchronization 
therapy. Circulation 2011;123:70-8. 

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6. Singh JP, Klein HU, Huang DT, et al.  Left ventricular lead position and clinical 
outcome in the multicenter automatic defibrillator implantation trial-cardiac 
resynchronization therapy (MADIT-CRT) trial.  Circulation 2011;123(11):1159-
1166.  
7. Donal E, Meunier C, et al. for the REVERSE study group. Sites of left and right 
ventricular lead implantation and response to cardiac resynchronization therapy 
observations from the REVERSE trial.  European Heart Journal 2012, 33: 2662-2671 
8. Singh JP, Fan D, Heist KE, et al. Left ventricular lead electrical delay predicts 
response to cardiac resynchronization therapy.  Heart Rhythm 2006;3:1285–1292. 
9. Gold MR, Birgersdotter-Green U, Singh JP, et al. The relationship between 
ventricular electrical delay and left ventricular remodelling with cardiac 
resynchronization therapy.  Eur Heart J 2011;32(20):2516-2524.  
10. Khan FZ, Virdee MS, Palmer CR, et al. Targeted left ventricular lead placement to 
guide cardiac resynchronization therapy: the TARGET study: a randomized, 
controlled trial.  J Am Coll Cardiol 2012;59:1509-1518.  
11. Saba S1, Marek J, Schwartzman D, Jain S, Adelstein E, White P, Oyenuga OA, 
Onishi T, Soman P, Gorcsan J 3rd.  Echocardiography-guided left ventricular lead 
placement for cardiac resynchronization therapy: results of the Speckle Tracking 
Assisted Resynchronization Therapy for Electrode Region trial.  Circ Heart Fail. 
2013;6(3):427-434.  
12. D'Onofrio A, Botto GL, Mantica M, et al. The interventricular conduction time is 
associated with response to cardiac resynchronization therapy, Int. J. Cardiol. 
2013;168  5067–5068.  
13. D'Onofrio A, Botto G, Mantica M, et al. Incremental value of larger interventricular 
conduction time in improving cardiac resynchronization therapy outcome in patients 
with different QRS duration, J. Cardiovasc. Electrophysiol. 2014;25:500–506.  
14. Gold MR, Singh JP, Ellenbogen KA, Yu Y, Wold N, Meyer TE, Birgersdotter-
Green.  Interventricular Electrical Delay Is  Predictive of Response to 
Cardiac Resynchronization Therapy.  J Am Coll Cardiol EP 2016;2:438-447. 
15. Abraham WT, Leon AR, Hannon C, Prather W, Fieberg A. Results of the InSync III 
Marquis Clinical Trial (abstract). Heart Rhythm 2005;2(5):S65. 
16. Rao RK, Kumar UM, Schafer J, Viloria E, De Lurgio D, Foster E. Reduced 
ventricular volumes and improved systolic function with cardiac resynchronization 
therapy: a randomized trial comparing simultaneous biventricular pacing, sequential 
biventricular pacing, and left ventricular pacing. Circulation 2007;115(16):2136-44. 
17. Baker JH, Turk K, Pires LA, et al. Optimization of interventricular delay in 
biventricular pacing: Results from the RHYTHM ICD V-V Optimization Phase 
Study. Heart Rhythm 2005; P3-96. 
18. Boriani G, Kranig W, Donal E, et al. A randomized double-blind comparison of 
biventricular versus left ventricular stimulation for cardiac resynchronization therapy: 

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the Biventricular versus Left Univentricular Pacing with ICD Back-up in Heart 
Failure Patients (B-LEFT HF) trial. Am Heart J 2010;159(6):1052-8. 
19. Martin DO, Lemke B, Birnie D, et al. Investigation of a novel algorithm for 
synchronized left-ventricular pacing and ambulatory optimization of cardiac 
resynchronization therapy: results of the adaptive CRT trial. Heart Rhythm 
2012;9(11):1807-14. 
20. Abraham WT, Gras D, Yu CM, et al. Results from the FREEDOM Trial 
(abstract).  Heart Rhythm 2010;7(5):2-3. 
21. Ellenbogen KA, Gold MR, Meyer TE, et al. Primary results from the SmartDelay 
determined AV optimization:  a comparison to other AV delay methods used in 
cardiac resynchronization therapy (SMART-AV) trial: a randomized trial comparing 
empirical, echocardiography guided, and algorithmic atrioventricular delay 
programming in cardiac resynchronization therapy. Circulation 2010;122:2660-8. 
22. Brugada Terradellas J, Delnoy PP, Brachmann J, et al.  Clinical response to CRT with 
the SonR contractility sensor: The RESPOND-CRT Study.  Oral presentation at Heart 
Rhythm Society, May 4-7, 2016, San Francisco CA. 
23. Menardi E BG, Goletto C, Rossetti G, Vado A. Characterization of ventricular 
activation pattern and acute hemodynamics during multipoint left ventricular pacing. 
Heart Rhythm. 2015;12:1762-1769. 
24. Pappone C ĆŽ, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Saviano 
M, Baldi M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, 
Fundaliotis A, Tavazzi L, Santinelli V. Multipoint left ventricular pacing improves 
acute hemodynamic response assessed with pressure-volume loops in cardiac 
resynchronization therapy patients. Heart Rhythm. 2014;11:394-401. 
25. Pappone C ĆŽ, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Jordan CD, Romano 
E4, Baldi M, Saviano M, Pappone A, Vitale R, Catalano C, Ciaccio C, Ciannelli L, 
Ionescu B, Petretta A, Fragakis N, Fundaliotis A, Tavazzi L, Santinelli V. Improving 
cardiac resynchronization therapy response with multipoint left ventricular 
pacing:  Twelve-month follow-up study. Heart Rhythm. 2015;12:1250-1258. 
26. Rinaldi CA KW, Leclercq C, et al. Acute effects of multisite left ventricular pacing 
on mechanical dyssynchrony in patients receiving cardiac resynchronization therapy. 
Journal of Cardiac Failure 2013;19:731-8. 
27. Rinaldi CA LC, Kranig W, Kacet S, Betts T, Bordachar P, Gutleben KJ, Shetty A, 
Donal E, Keel A, Ryu K, Farazi TG, Simon M, Naqvi TZ. Improvement in acute 
contractility and hemodynamics with multipoint pacing via a left ventricular 
quadripolar pacing lead. J Interv Card Electrophysiol. 2014;40:75-80. 
28. Thibault B DM, Khairy P, Guerra PG, Macle L, Rivard L, Roy D, Talajic M, Karst E, 
Ryu K, Paiement P, Farazi TG. Acute haemodynamic comparison of multisite and 
biventricular pacing with a quadripolar left ventricular lead. Europace. 2013;15:984-
991. 

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29. Zanon F BE, Pastore G, Marcantoni L, Fraccaro C, Lanza D, Picariello C, Aggio S, 
Roncon L, Dell'Avvocata F, Rigatelli G, Pacetta D, Noventa F, Prinzen FW. 
Multipoint pacing by a left ventricular quadripolar lead improves the acute 
hemodynamic response to CRT compared with conventional biventricular pacing at 
any site. Heart Rhythm. 2015;12:975-981. 
30. Zanon F ML, Baracca E, Pastore G, Lanza D, Fraccaro C, Picariello C, Conte L, 
Aggio S, Roncon L, Pacetta D, Badie N, Noventa F, Prinzen FW. Optimization of left 
ventricular pacing site plus multipoint pacing improves remodeling and clinical 
response to cardiac resynchronization therapy at 1 year. Heart Rhythm. 
2016;13:1644-1651. 
31. Forleo GB SL, Giammaria M, Potenza D, Curnis A, Calabrese V, Ricciardi D, 
D'agostino C, Notarstefano P, Ribatti V, Morani G, Mantica M, Di Biase L, Bertaglia 
E, Calò L, Zanon F. Multipoint pacing via a quadripolar left-ventricular lead: 
preliminary results from the Italian registry on multipoint left-ventricular pacing in 
cardiac resynchronization therapy (IRON-MPP). Europace. 2016;Epub ahead of print. 
32. Tomassoni G, Baker J, Corbisiero R, et al.  Safety and efficacy of multipoint pacing 
in cardiac resynchronization therapy: The MultiPoint Pacing IDE Trial.  Oral 
presentation at Heart Rhythm Society, May 4-7, 2016, San Francisco CA. 
 
26. Appendix Detailed Information on Running Features Testing 
 
Only as guidance, if needed below details on the different features. 
26.1. Detailed steps on obtaining the data from the SmartDelay test 
Step 1. Navigate to the SmartDelay Optimization screen  
 From the programmer (PRM) main screen, choose the Settings tab. 
 From the Settings tab, choose Settings – Normal Brady/CRT,  
 From the Settings – Normal Brady/CRT screen, choose SmartDelay Optimization. 
Step 2. Run the SmartDelay test 
 From the SmartDelay Optimization screen, choose Start Test. The test typically lasts 
up to 2.5 minutes. 
 Set the LRL at 10 to 15 beats above the subject’s intrinsic heart rate.  
 Set EGM channels to RA, RV, and LV. Obtain ECG/EGM strips at the paper speed of 
100 mm/s for approximately 5-10 representative beats in both the Atrial Sense test 
and Atrial Pace test. Measure values for Asense-RVsense, Asense-LVsense, Apace-
RVsense, and Apace-LVsense intervals from the ECG/EGM strips 

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 SmartDelay will recommend AV delay and Pacing Chamber (BiV or LV Only).  
 If the SmartDelay test fails, the nominal value will be displayed. 
Step 3. Program AV Delays and Pacing Chambers 
 If following the recommended AV Delay and Pacing Chamber value determined by 
the SmartDelay, choose Copy Suggested Settings and select the Program button to 
program the device. 
 If not following the recommended AV Delay and Pacing Chamber value determined 
by SmartDelay,  
o Manually record the SmartDelay recommendation before exiting the test 
screen. Print a copy of the Settings Changes Report before any changes are 
made and programmed to document the recommended values from the 
SmartDelay test 
o Manually enter the desired values in the Settings – Normal Brady/CRT screen, 
and select the Program button to program the device. 
Step 4. Record the recommended and programmed value  
 Record in the corresponding Clinic Visit eCRFs both the SmartDelay 
recommendation and final programmed value for AV Delay and Pacing Chamber. 
26.2. Detailed steps on obtaining the data from the LV VectorGuide test 
Step 1. Navigate to the LV VectorGuide Screen 
 From the programmer (PRM) summary tab: choose TESTs. 
 From the TESTs screen: choose Lead Tests.  
 From the Lead Tests screen: choose LV VectorGuide.  
Or (for MSP) 
 From the programmer (PRM) summary tab: choose Settings Summary. 
 From the Settings Summary screen: choose Normal Brady/CRT screen.  
 From the Normal Brady/CRT screen: choose LV MultiSite Pacing.  
 From the LV MultiSite Pacing screen: choose Run LV VectorGuide. 
Step 2. Select the vectors to be tested with LV VectorGuide 
Step 3. Run the RVS-LVS delay test for the selected vectors.   
 Subjects must have LV and RV sensed beats for test to be successful. If the subject 
does not tolerate a low intrinsic heart rate, stop the test. 
Step 4. Run the lead impedance test for the selected vectors.  
 The range of out-of-range pacing impedance value is programmable. 

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Step 5. Run the PNS test for the selected vectors (the pacing voltage and pulse width 
are at physician’s discretion).   
Step 6. Run the LV Threshold Test for the selected vectors 
 There are 3 methods available to test the LV Threshold – Quick Capture, Auto 
Amplitude, or Amplitude Test.   
 The nominal setting to test the LV threshold is 2.5V @ 0.4 ms; however, it can be 
reprogrammed at physician’s discretion. 
Step 7. Print LV VectorGuide Report to record test results. 
 Navigate to the Report screen by choosing Report button at the bottom of the LV 
VectorGuide screen. 
 Select LV VectorGuide Report. 
 Select both Print Selected Report and Save Report for later retrieval of the report.  
 Record test results in the Post Implant and follow-up eCRFs. 
 
26.3. Detailed steps on running SmartVector test 
Step 1. After running LV VectorGuide, navigate back to Settings – LV Multisite 
Pacing Configuration screen 
Step 2. Run the SmartVector function: 
 Under Set LV Multisite Pacing Value, select Pacing Order button and choose either 
LVa to LVb to RV for LV MSP BiV pacing or LVa to LVb for LV MSP LV Only 
Pacing. 
 Under Set LV Multisite Pacing Value, choose the SmartVector button. 
 The SmartVector function will recommend LVa and LVb pacing vectors.   
 Print a copy of the Setting Changes Report before setting changes are made and 
programmed to show the recommended LVa and LVb vectors. 
 If not following SmartVector recommendation, investigator may enter LVa and LVb 
vectors manually. 
Step 3. Record both SmartVector recommended vectors and final programmed 
vectors.   
 Record the values in the follow-up eCRFs. If not following SmartVector 
recommendation, record the rationale. 
26.4. Detailed steps on running SmartOffset test 
Step 1. Run the SmartOffset function: 
 From the Settings – LV MultiSite Pacing screen, select the SmartOffset button.