Tragus Stimulation to Prevent Atrial Fibrillation After Cardiac Surgery: The TraP-AF Study
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: University of Chicago

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Version:  2019Mar11 
PROTOCOL TITLE:  
TRAGUS STIMULATION TO PREVENT ATRIAL FIBRILLATION AFTER CARDIAC SURGERY: THE 
TRAP-AF STUDY 
 
 
PI: GAURAV A. UPADHYAY, MD 
 
 
CO-I(S): RODERICK TUNG, MD, HEMAL NAYAK, MD; ZAID AZIZ MD, ANDREW BEASER MD; 
MICHAEL BROMAN, MD PHD; CEVHER OZCAN, MD, VALLUVAN JEEVANANDAM, MD, HUSAM 
BALKHY, MD, TAKEYOSHI OTA, MD, TAE SONG, MD, DAVID ONSAGER, MD, SUNNY PO, MD 
 
 
FUNDING: INTERNAL 
 
 
SPONSOR: NONE 
 
 
TYPE OF RESEARCH: CLINICAL TRIAL 
 
 
INTERVENTION: TRANSCUTANEOUS LOW-LEVEL TRAGUS STIMULATION (LLTS) 
 
 
MANUFACTURER OF INTERVENTION: NOT APPLICABLE 
 
 
IND OR IDE # NOT APPLICABLE 

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Version:  2019Mar11 
STUDY SUMMARY 
TITLE 
Tragus Stimulation to Prevent Atrial Fibrillation after 
Cardiac Surgery 
SHORT TITLE 
The TraP-AF Study 
PROTOCOL NUMBER 
IRB17-1365 
METHODOLOGY 
Single-blind clinical trial 
STUDY DURATION 
1 year 
STUDY CENTER(S) 
Single-center 
OBJECTIVES 
To compare the effectiveness of transcutaneous low-level 
tragus stimulation (LLTS) of the auricular branch of the 
vagus nerve versus sham in the prevention of postoperative 
atrial fibrillation (POAF) after cardiac surgery. 
NUMBER OF SUBJECTS 
80 patients 
DIAGNOSIS AND MAIN INCLUSION 
CRITERIA 
Patients undergoing coronary artery bypass graft (CABG) 
surgery and/or valve surgery who are 18 years of age or 
older at the University of Chicago will be eligible for 
evaluation for inclusion into this study. Exclusion criteria 
include:  
1) Prior history of persistent or permanent atrial 
fibrillation (AF) as determined by detailed chart review 
2) Emergency cases 
3) Pregnant patients 
4) Patients undergoing the following procedures: heart 
transplant, pulmonary thromboendarterctomy, isolated 
aortic arch procedures, ventricular assist device 
insertion, extracorporeal membrane oxygenation 
insertion, and surgical AF ablation 
STUDY PRODUCT 
Transcutaneous low-level tragus stimulation (LLTS) is a 
completely noninvasive technique which utilizes an FDA 
approved transcutaneous electrical nerve stimulation 
(TENS) device (Parasym, Parasym Health). This device 
consists of a battery-powered, programmable 
transcutaneous electrical nerve stimulation (TENS) unit and 
a pair of stimulation electrodes that can be clipped to the 
tragus of the externl ear in order to stimulate the auricular 
branch of the vagus nerve. 
DURATION OF ADMINISTRATION  
LLTS will be administered continuously for 48 hours, 
beginning immediately after surgery. The stimulator will be 
shifted from one ear to the other every 4 hours. 

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Version:  2019Mar11 
REFERENCE THERAPY  
The reference therapy will be a sham control group; i.e., 
patients on whom an LLTS device with a non-functioning 
electrode will be applied and in whom therapy will not be 
delivered. 
STATISTICAL METHODOLOGY  
Traditional statistical methods will be employed. The 
student’s T-test will be used for continuous comparisons. 
Fisher’s exact or the Chi-square test will be applied for 
dichotomous variables. Time to endpoint analysis will be 
performed using the Kaplan-Meier method. 
 

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Version:  2019Mar11 
LIST OF ABBREVIATIONS 
 
AAD  
 
ANTIARRHYTHMIC DRUG THERAPY 
ACE-I  
 
ANGIOTENSIN-CONVERTING ENZYME INHIBITOR 
AF 
 
 
ATRIAL FIBRILLATION 
ARB  
 
ANGIOTENSIN RECEPTOR BLOCKER 
BB 
 
 
BETA-BLOCKER 
CABG  
 
CORONARY ARTERY BYPASS GRAFT 
CRT 
 
 
CARDIAC RESYNCHRONIZATION THERAPY 
FDA  
 
FOOD AND DRUG ADMINISTRATION 
GDMT 
 
GOAL-DIRECTED MEDICAL THERAPY 
HF 
 
 
HEART FAILURE 
ICD 
 
 
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR 
IRB 
 
 
INSTITUTIONAL REVIEW BOARD 
LBBB  
 
LEFT BUNDLE-BRANCH BLOCK 
LV 
 
 
LEFT VENTRICULAR 
LLTS  
 
LOW-LEVEL TRAGUS STIMULATION 
LVEF  
 
LEFT VENTRICULAR EJECTION FRACTION 
NYHA  
 
NEW YORK HEART ASSOCIATION 
POAF  
 
POSTOPERATIVE ATRIAL FIBRILLATION 
POD  
 
POSTOPERATIVE DAY 
RA 
 
 
RIGHT ATRIUM 
RV 
 
 
RIGHT VENTRICLE 
SR 
 
 
SINUS RHYTHM 
TTE 
 
 
TRANSTHORACIC ECHOCARDIOGRAM 
UCMC 
 
UNIVERSITY OF CHICAGO MEDICAL CENTER 
UOFC  
 
UNIVERSITY OF CHICAGO 
 
VT 
 
 
VENTRICULAR TACHYCARDIA 
 
VF 
 
 
VENTRICULAR FIBRILLATION 

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Version:  2019Mar11 
1.  INTRODUCTION  
 
A. BACKGROUND AND RATIONALE 
 
New-onset postoperative atrial fibrillation (POAF) commonly complicates cardiac surgery, 
affecting between 20 and 50% of patients,1 with an even higher risk for patients undergoing 
combined coronary artery bypass graft (CABG) and/or valve replacement procedures.2,3 The 
spectrum of POAF varies from self-limited episodes to persistent AF requiring antiarrhythmic 
drug therapy (AAD) and cardioversion.  
Overall, POAF portends significantly worse clinical outcomes, including an up to four-fold 
increased risk of stroke and doubling of both all-cause 30-day and 6 month mortality.4 In 
addition, POAF is independently associated with prolonged intensive care unit (ICU) stays, 
longer overall duration of hospitalization (extending length-of-stay by 2 to 5 days), and 
significantly increased costs by $10,000-20,000, even during the index hospitalization.4,5 POAF 
usually occurs between 2 and 4 days after surgery, with a peak incidence on postoperative day 
2.6 The pathogenesis of POAF in the cardiac surgical setting remains poorly understood, 
although there is data to suggest that autonomic imbalance during the post-operative period may 
play a key role for some patients.1 
Peripheral vagal nerve stimulation can alter central parasympathetic cardiac inputs, leading to 
reduced heart rate along with reduced dispersion of atrial effective refractory periods (AERPs), 
lowering the risk of AF.7,8 While direct vagal nerve stimulation has an established role in the 
treatment of intractable epilepsy and treatment-resistant depression,9,10 its application for POAF 
has been limited due to its invasive nature and increased risks.  
Transcutaneous low-level tragus stimulation (LLTS), however, has recently emerged as a 
novel, entirely noninvasive means to achieve vagal nerve stimulation, which achieves 
anticholinergic and antiadrenergic effects.11 The auricular branch of the vagus nerve localizes to 
the skin near the anterior protuberance of the outer ear, called the tragus. LLTS has been shown 
to significantly suppress AF inducibility, reduce overall AF duration, and reduce the production 
of inflammatory cytokines (i.e., TNF-alpha and C-reactive protein) in acute studies.12-15 
Furthermore, it may have additional benefits in inducing autonomic remodeling, as well as 
reducing ventricular arrhythmia.16 The Parasym devicedelivers LLTS through the skin via the 
outer ear (see Appendix A, Figures 1-2). It has been used in a variety of medical treatments, 
including tinnitus, depression, anxiety, and rheumatoid arthritis. We seek to evaluate the role of 
LLTS in preventing POAF, reducing AF duration, reducing average length of stay, and reducing 
overall arrhythmia incidence after cardiac surgery. 
 
B.  OBJECTIVES  
 
We hypothesize that: 
a. In patients undergoing cardiac surgery (i.e., CABG and/or valve surgery), new-onset 
POAF is common 
b. LLTS is a simple, noninvasive and effective means to reduce the incidence of POAF, 
reduce overall AF duration, and reduce incidence of significant ventricular arrhythmias 
(i.e., nonsustained or sustained VT/VF) 
c. Use of LLTS in the inpatient setting leads to reduced overall AF and reduced AF duration 
in the 30-day period after cardiac surgery 

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Specific aims: 
Aim 1: To determine the overall rate of successful LLTS in the inpatient setting. Patients 
randomized to LLTS will undergo continuous stimulation for two inpatient days. Tolerance of 
LLTS versus sham will be assessed. 
 
Aim 2: To assess the impact of LLTS on acute and short-term outcomes. Acute outcomes 
include the incidence of inpatient POAF during the index hospitalization, length of hospital stay, 
overall AF duration, and incidence of nonsustained or sustained VT/VF. Short-term outcomes 
include incidence of AF as assessed by 14-day monitor (i.e. Zio patch or CardioNet event 
monitor) upon discharge. 
 
2.  STUDY DESIGN  
 
Study design: Single-blind study. Patients will be randomized, to LLTS versus sham procedure, 
and remain blinded to their treatment allocation. Both treatment options will utilize similar 
equipment, namely the use of alligator clips which will be placed on the tragus and earlobe of the 
right ear for patients (see Appendix A, Figure 2). The distinction is only that in patients assigned 
to LLTS, they will be initiated on therapy at the time of device placement. 
 
Prior to cardiac surgery, the discomfort threshold of both left and righ tragus stimulation will be 
determined for all participating patients. Intermittent electrode signals, or microcurrents, are 
delivered at 20 Hz with 200 µsec pulse width with variable microampere (mA) output. The 
discomfort threshold is defined as the stimulation intensity in mA at which point patients 
experience discomort. The stimulation intensity used in the study will be set just below the 
discomfort threshold, as established from prior work.15 The clip will then be placed on the 
patient’s ear at the end of surgery. After surgery is completed, the clip will then be removed and 
replaced on the contralateral ear. Stimulation will then continue, one ear alternating with the 
other, every 4 hours for a total of 48 hours. It is possible that the threshold can change during the 
post-operative period. If the patient shows any sign of discomfort from stimulation, the intensity 
of stimulation will be reduced to a level at which signs of discomfort disappears. 
 
Follow-up will be performed with 14-day event monitor (i.e. Zio patch or CardioNet event 
monitor) at the time of discharge. 
 
Electrocardiography (i.e. ECG) will be performed pre-procedure and prior to hospital discharge. 
Echocardiography will be assessed prior to study initiation and when clinically available in 
follow-up. 
 
Duration of study: 1 month 
 
Primary endpoints: A combination of clinical and electrocardiographic endpoints will be 
prospectively studied. These include: 
- 
Clinical: Primary clinical endpoint is time to inpatient AF (length of stay >5 days). 
Secondary endpoint is any occurance of AF during 14 day post procedure monitoring.  . 
- 
Electrocardiographic: Arrhythmia occurrence (i.e., AF, nonsustained VT, VT or VF 
requiring device therapy) will be documented throughout the study period 

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Primary safety endpoint: Procedure-related complications will be assessed prospectively both 
acutely and throughout the study period, including:  
- 
Procedure related: pain, tragus site abrasion or bruising 
 
Randomization scheme: Patients will be allocated to LLTS or sham in a 1:1 ratio at time of 
implant based on random number generator. 
 
3.  SUBJECT SELECTION AND WITHDRAWAL  
 
Sites: 
Subjects selected for study will be recruited from the University of Chicago Medical Center 
(Chicago, IL). 
 
Eligibility: 
Eligible patients will be all patients undergoing CABG and/or valve surgery.  
 
Inclusion Criteria: 
1. Patients ≥18 years of age, <90 years of age 
2. Estimated life expectancy of at least 1 year at the time of enrollment 
3. History of sinus rhythm or paroxysmal atrial fibrillation 
 
Exclusion Criteria: 
1. Patients ≥90 years of age, <18 years 
2. Patients with known prior history of persistent or permanent AF 
3. Atrial Fibrillation occurance  within the last 24 hours of procedure 
4. Urgent or Emergency cases 
5. Pregnant patients 
6. Patients undergoing the following cardiac procedures: heart transplant, pulmonary 
thromboendarterctomy, isolated aortic arch procedures, congenital hear disease, 
ventricular assist device insertion, extracorporeal membrane oxygenation insertion, 
and surgical AF ablation 
7. Antiarrhythmics prior to surgery (Class I and Class III) 
8. High degree AV block requiring temporary pacing 
9. MAZE procedure 
 
4.  STUDY DEVICE  
 
LLTS will be performed using a transcutaneous electrical nerve stimulation (TENS) device 
(Parasym, Parasym Health). This device consists of a battery-powered, programmable TENS unit 
and a pair of stimulation electrodes that can be clipped to the tragus of the externl ear in order to 
stimulate the auricular branch of the vagus nerve (see Appendix A, Figures 1-2). There is no 
known interaction with other cardiac devices (e.g., pacemakers and defibrillators) 
 

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Version:  2019Mar11 
The device was cleared by the FDA as a Class II device based on Section 882.5890 (see 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfrl/ldetails.cfm?lid=157705). This is a non-
significant risk device. It has not been subject to any advisories or recalls. 
 
5.  STUDY PROCEDURES 
 
Pre-Stimulation: 
- 
Patients will be screened for study 
- 
Discomfort threshold bilaterally will be measured (20 Hz) for 5 minutes 
- 
Pre-implant ECG reviewed (to be performed on day of screening) 
- 
Baseline transthoracic echocardiogram (TTE) reviewed (does not need to be performed 
during inpatient hospitalization; outpatient or outside-hospital TTE report may also be 
performed) 
- 
NYHA functional class to be determined by treating physician 
- 
Operating physician will be informed of patient randomization allocation to facilitate 
planning of procedure 
 
Randomization, Implant, and Periprocedure Care: 
- 
LLTS or sham will instituted upon arrival in PACU/recovery after surgery with right 
sided LLTS.  The site of stimulation will alternate every 4 hours between right and left 
tragusfor total stimulation duration of 48 hours. 
- 
Postoperative care for the cardiac surgical patient will be performed as per routine 
standard of care by the treating primary team 
- 
The patient will be maintained on telemetry during the entire inpatient hospitalization 
- 
Telemetry will be checked daily to evaluate for any new-onset AF 
- 
Predischarge ECG will be performed at the time of hospital discharge 
- 
The patient will be fitted with a 14-day event monitor (i.e. Zio patch or Cardionet 
monitor) at the time of discharge or to be mailed to the patient/picked-up by patient 
immediately after discharge on a weekend discharge day 
- 
Blood will be collected for C-reactive protein measurement to assess inflammation per 
routine lab assessments 
 
Follow-Up Visit (can be performed between 2 weeks and 1 month after discharge): 
- 
The patient will return the 14-day monitor, if not already mailed back 
- 
Routine clinical check as per primary team 
 
Future contact: 
- 
Patients will be asked to participate in an extended registry (protocol IRB16-0272) to 
evaluate longer-term clinical outcome after study completion.  Patients will be asked to 
sign a separate consent form for participation in this study. 
 
6.  STATISTICAL PLAN AND CONSIDERATIONS 
 
Primary Outcome: 
1. Time to the first episode of AF >30 seconds during inpatient admission or within 14-day 
monitoring period 

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a. In hospital: full-disclosure telemetry 
b. Time to AF will be assessed by physicians blinded to randomization 
2. Extended hospitalization of >5 days 
 
Secondary Outcomes: 
1. Overall AF burden, as assessed by 2 week monitor (CardioNet or Zio Patch) upon 
discharge 
2. Inflammatory markers: C-reactive protein (ordered if clinically indicated) 
3. Actionable AF: antiarrhythmic use (including rate-control meds), CDV, anticoagulation, 
use of inotropes for BP support during AF 
4. Stroke or transient ischemic attack (TIA) 
5. All cause of mortality 
 
Sample size estimation: 
Assuming a two-armed study with composite endpoint of occurrence of AF or >5 days 
hospitalization, whereby the treatment group will have 50% likelihood of the event occurring and 
a control group will have 20% likelihood of the event occurring, as well as a 10% dropout rate, 
we will be able to detect differences in 80 patients (40 in each arm).  Under these assumptions 
and using two-sided Z-Test with unpooled variance to compare the changes between these two 
groups, we will have 80% power (α=0.05) to detect a difference between the group proportions 
of 0.30.  PASS software Version 15 (NCSS, LLC, Kaysville, UT) was used to calculate the 
statistical power. 
 
Statistical methods: 
Patients will be studied based on the randomization allocation. Patients who refuse to continue 
with study treatment (i.e. they refuse to wear ear clip) during time of therapy will be analyzed as 
intention-to-treat per allocation group. Fisher’s exact or the Chi-Square test will be used for 
categorical variables, and continuous parameters will be compared by the two-tailed unpaired 
Student’s t test and the F test for analysis of variance (ANOVA), as needed. Kaplan-Meier method 
will be used for computing the event free survival curves. Each strategy will be compared within 
this cohort of patients for its impact on percent incidence of POAF and length of stay. Multiple 
logistic regression and multiple regressions using the Cox proportional hazards model will be 
performed to determine the independent association of each of the demographic variables with 
clinical outcome.  
 
7.  RISKS AND BENEFITS 
 
Risks: 
LLTS is a novel, entirely noninvasive means to stimulate the auricular branch of the vagus nerve. 
There are risks associated with alligator clip application which will be similar in the two groups; 
these risks include discomfort to the tragus or skin abrasion. There is discomfort with high level 
stimulation, and at the time of neuromodulation, strict attention to patient comfort will be 
maintained. 
 
Benefits: 

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Version:  2019Mar11 
There are significant possible benefits to this treatment. Should LLTS be effective at reducing 
postoperative AF, this would be associated with significant benefit to the patient as well as 
potentially lead to a significant improvement in overall postoperative management of patients. 
 
8.  SAFETY AND ADVERSE EVENTS  
 
Safety: 
As noted above, periprocedural complications will be logged with respect to procedure, system-
related, and lead-related events. All complications will be independently reviewed at the 
midpoint by the primary investigator (PI). Should there be a trend towards increased 
complication risk, the study will be halted. 
 
Adverse Events: 
As noted above, all adverse events associated with devices will be monitored periprocedurally 
and continuously through the study. The PI will independently review all events after 
randomization of 20 subjects in order to make a determination for continuance. 
 
Adverse Effect Documentation: 
1. Sinus bradycardia or AVB after sitmulation 
2. Discomfort or possible skin abrasion due to tragus stimulation 
3. Major organ-system failure 
4. Death 
 
9.  DATA HANDLING AND RECORD KEEPING  
 
Data will be collected on paper by study coordinators and transcribed into a RedCap database, 
which will be maintained at the Uof C. Data will be managed by the PI and study coordinators, 
and only the study team will have access to the data. All patient-specific identifiers will be kept 
separate from the primary research database. The research database will be organized by a 
unique patient code. 
 
10.  STUDY MONITORING, AUDITING AND INSPECTING 
 
All periprocedural complications and adverse events will be reviewed by the PI at study 
midpoint to ensure there is no significant difference in event rate between the study groups. 
Should there be significant differences, or if there should be a high overall event-rate out-of-line 
with the procedural norm for AF, the study will be halted. 
 
11.  FINANCIAL CONSIDERATIONS 
 
No renumeration will be provided to subjects. 
 
12.  ETHICAL CONSIDERATIONS 
 
No specific ethical considerations are identified in relation to this study. 
13.  CONFLICT OF INTEREST 

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This is an internally funded study with no external support. 
 
14.  REFERENCES  
 
1. 
Echahidi N, Pibarot P, O'Hara G, Mathieu P. Mechanisms, prevention, and treatment of 
atrial fibrillation after cardiac surgery. J Am Coll Cardiol 2008;51:793-801. 
2. 
Bessissow A, Khan J, Devereaux PJ, Alvarez-Garcia J, Alonso-Coello P. Postoperative 
atrial fibrillation in non-cardiac and cardiac surgery: an overview. J Thromb Haemost 2015;13 
Suppl 1:S304-12. 
3. 
Helgadottir S, Sigurdsson MI, Ingvarsdottir IL, Arnar DO, Gudbjartsson T. Atrial 
fibrillation following cardiac surgery: risk analysis and long-term survival. J Cardiothorac Surg 
2012;7:87. 
4. 
Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation 
following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg 2017. 
5. 
Mathew JP, Parks R, Savino JS, et al. Atrial fibrillation following coronary artery bypass 
graft surgery: predictors, outcomes, and resource utilization. MultiCenter Study of Perioperative 
Ischemia Research Group. JAMA 1996;276:300-6. 
6. 
Melby SJ, George JF, Picone DJ, et al. A time-related parametric risk factor analysis for 
postoperative atrial fibrillation after heart surgery. J Thorac Cardiovasc Surg 2015;149:886-92. 
7. 
Li S, Scherlag BJ, Yu L, et al. Low-level vagosympathetic stimulation: a paradox and 
potential new modality for the treatment of focal atrial fibrillation. Circ Arrhythm Electrophysiol 
2009;2:645-51. 
8. 
Ajijola OA, Hamon D. Non-Invasive Neuromodulation Via Tragal Stimulation: Time to 
Lend an Ear? JACC Clin Electrophysiol 2016;2:340-2. 
9. 
Ching J, Khan S, White P, et al. Long-term effectiveness and tolerability of vagal nerve 
stimulation in adults with intractable epilepsy: a retrospective analysis of 100 patients. Br J 
Neurosurg 2013;27:228-34. 
10. 
Henderson JM. Vagal nerve stimulation versus deep brain stimulation for treatment-
resistant depression: show me the data. Clin Neurosurg 2007;54:88-90. 
11. 
Sha Y, Scherlag BJ, Yu L, et al. Low-level right vagal stimulation: anticholinergic and 
antiadrenergic effects. J Cardiovasc Electrophysiol 2011;22:1147-53. 
12. 
Yu L, Scherlag BJ, Li S, et al. Low-level vagosympathetic nerve stimulation inhibits 
atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. 
J Cardiovasc Electrophysiol 2011;22:455-63. 
13. 
Sheng X, Scherlag BJ, Yu L, et al. Prevention and reversal of atrial fibrillation 
inducibility and autonomic remodeling by low-level vagosympathetic nerve stimulation. J Am 
Coll Cardiol 2011;57:563-71. 
14. 
Shen MJ, Shinohara T, Park HW, et al. Continuous low-level vagus nerve stimulation 
reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory 
canines. Circulation 2011;123:2204-12. 
15. 
Stavrakis S, Humphrey MB, Scherlag BJ, et al. Low-level transcutaneous electrical vagus 
nerve stimulation suppresses atrial fibrillation. J Am Coll Cardiol 2015;65:867-75. 
16. 
Lilei Yu SW, Ziaoya Zhou, Zhuo Wang, Bing Huang, Kai Liao, Gaowa Saren, Mingxian 
Chen, Sunny S. Po, Hong Jiang. Chronic Intermittent Low-Level Stimulation of Tragus Reduces 

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Cardiac Autonomic Remodeling and Ventricular Arrhythmia Inducibility in a Post-Infarction 
Canine Model. Journal of the American College of Cardiology EP 2016;2:330-9. 
 
15.  APPENDIXES 
 
A. FIGURES 
 
Figure 1: Parasym Device 
 
 

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Figure 2: Electrode attached to tragus 
 
 
 
B. J AM COLL CARDIOL 2015;65:867–75 
 
Low-level 
transcutaneous stimu 

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C. SCHEDULE OF EVENTS (SCHEMA) 
 
 
Screening 
Surgery 
(Day 0) 
Post-Op 
Days 1-2 
Day of 
Discharge 
Follow-Up Visit 
(2 weeks to 1 
month after 
discharge) 
Medical Records 
Review 
X 
 
 
 
X 
Clinical Evaluation 
(Physical Exam, 
Vital Signs, 
Medication Review) 
X 
X 
X 
X 
X 
Electrocardiogram 
X 
 
 
X 
 
Echocardiogram 
Xa 
 
 
 
Xa 
Urine Pregnancy 
Test 
Xb 
 
 
 
 
NYHA Functional 
Class Determination 
X 
 
 
 
 
Randomization 
Xc 
 
 
 
 
LLTS or Sham 
Application 
 
Xd 
Xe 
 
 
C-Reactive Protein 
Blood Test 
 
Xf 
Xf 
 
 
Event Monitor (i.e. 
Zio Patch or 
Cardionet Monitor) 
 
 
 
Xg 
X 
Adverse Events 
 
X 
X 
X 
X 
 
a Results from records review, if available 
b Only for women of childbearing potential 
c Pre-procedure to facilitate planning of procedure 
d Immediately after surgery 
e Continuous for 48 hours 
f If clinically indicated 
g Pre-discharge if discharged on a weekday; arrangement for mailing or pick-up for patients 
discharged on a weekend day