NHLBI Transmural Electrosurgery LeafLet Traversal and Laceration Evaluation (TELLTALE) BASILICA-TAVR Trial
Phase: NA
Conditions: Valvular Heart Disease, Aortic Valve Failure
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

 
 Protocol with Statistical Analysis Plan Cover Page:   
 
Official Title: 
NHLBI Transmural Electrosurgery LeafLet Traversal And Laceration Evaluation 
(TELLTALE) BASILICA-TAVR Trial 
NCT number: 
 
NCT05666713 
Document Type:  
Protocol with Statistical Analysis Plan (SAP)  
Document Date: 
October 31, 2024 
 
 

Abbreviated Title: TELLTALE Trial 
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Abbreviated Title: TELLTALE Trial 
NIH Institutional Review Board (IRB) #: 000673H 
Version Date: 2024-10-31, Amendment C 
Title: NHLBI Transmural Electrosurgery LeafLet Traversal And Laceration Evaluation (TELLTALE) 
BASILICA-TAVR Trial 
Investigational Device: 
TELLTALE Electrosurgical Guidewire System 
IDE Number: 
G220207 
Sponsor: 
Office of Clinical Director, National Heart Lung and Blood 
Institute, National Institutes of Health, USA 
Sponsor Representative & 
NIH Principal Investigator 
Robert J. Lederman, MD 
Cardiovascular Branch, Division of Intramural Research, 
National Heart Lung and Blood Institute, National 
Institutes of Health, 
Building 10, Rm 2c713 MSC 1538, 9000 Rockville Pike 
Bethesda, MD 20892-1538 
Phone: +1-301-402-6769 
E-mail: lederman@nih.gov 
Data Coordinating Center: 
National Heart Lung and Blood Institute Division of 
Intramural Research 
Manufacturer: 
Transmural Systems, 4 Dundee Park Dr, Andover, MA, 
01810, USA 
Manufacturer Representative: 
Nasser Rafiee 
Data and Safety Monitoring 
Board (DSMB) 
National Heart Lung and Blood Institute 
 
 
 

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TABLE OF CONTENTS 
1 
STATEMENT OF COMPLIANCE ............................................................................................. 4 
2 
PROTOCOL SUMMARY ......................................................................................................... 5 
2.1 
Synopsis..................................................................................................................... 5 
2.2 
Schema .................................................................................................................... 10 
2.3 
Schedule of Activities (SOA) .................................................................................... 11 
2.4 
Blood tests .............................................................................................................. 12 
2.5 
Clinical versus research activities ........................................................................... 12 
3 
INTRODUCTION .................................................................................................................. 13 
3.1 
Public précis ............................................................................................................ 13 
3.2 
Background and Clinical Justification ..................................................................... 13 
3.3 
Risk/Benefit Assessment ......................................................................................... 21 
4 
OBJECTIVES AND ENDPOINTS ............................................................................................ 24 
4.1 
Objective ................................................................................................................. 24 
4.2 
Hypotheses ............................................................................................................. 25 
4.3 
Endpoint Design Considerations ............................................................................. 25 
4.4 
Primary Efficacy Endpoint ....................................................................................... 27 
4.5 
Primary Safety Endpoint ......................................................................................... 27 
4.6 
Secondary Endpoint: 30-day Safety ........................................................................ 28 
4.7 
Exploratory Endpoints ............................................................................................. 28 
5 
STUDY DESIGN ................................................................................................................... 29 
5.1 
Constant values ....................................................................................................... 29 
5.2 
Overall Design ......................................................................................................... 29 
5.3 
Scientific Justification for Initiating this Study ........................................................ 29 
5.4 
Scientific Justification for Duration of Study Follow-up ......................................... 30 
5.5 
Justification for single-arm study design ................................................................ 30 
6 
STUDY POPULATION .......................................................................................................... 31 
6.1 
Inclusion Criteria ..................................................................................................... 31 
6.2 
Exclusion Criteria..................................................................................................... 32 
6.3 
Enrollment Quota ................................................................................................... 32 
6.4 
Rationale for selection criteria................................................................................ 32 
6.5 
Inclusion of Vulnerable Subjects ............................................................................. 33 
6.6 
Lifestyle Considerations .......................................................................................... 33 
6.7 
Screen Failures ........................................................................................................ 33 
6.8 
Strategies for Recruitment and Retention .............................................................. 34 
7 
STUDY INTERVENTION ....................................................................................................... 34 
7.1 
Test articles and Indications for Use ....................................................................... 34 
7.2 
BASILICA-TAVR using the TELLTALE System ............................................................ 37 
7.3 
Preparation/Handling/Storage/Accountability ...................................................... 40 
7.4 
Measures to Minimize Bias: Randomization and Blinding ..................................... 40 
7.5 
Study Intervention Compliance .............................................................................. 40 
7.6 
Concomitant Therapy ............................................................................................. 40 
8 
DISCONTINUING OR WITHDRAWING STUDY INTERVENTION OR SUBJECT ....................... 40 
8.1 
Discontinuation of Study Intervention ................................................................... 40 

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8.2 
Aborted or abandoned TELLTALE BASILICA-TAVR .................................................. 40 
8.3 
Subject Discontinuation/Withdrawal from the Study ............................................ 41 
8.4 
Loss to Follow-up .................................................................................................... 41 
9 
STUDY ASSESSMENTS AND PROCEDURES ......................................................................... 41 
9.1 
Screening Procedures ............................................................................................. 41 
9.2 
Efficacy Assessments .............................................................................................. 42 
9.3 
Safety and Other Assessments ............................................................................... 42 
9.4 
Adverse Events and Serious Adverse Events .......................................................... 43 
9.5 
Unanticipated Problems ......................................................................................... 46 
9.6 
Protocol Deviations and Non-Compliance .............................................................. 47 
10 STATISTICAL CONSIDERATIONS ......................................................................................... 47 
10.1 
Statistical Hypothesis .............................................................................................. 47 
10.2 
Sample Size Determination ..................................................................................... 47 
10.3 
Cohorts for Analyses ............................................................................................... 49 
10.4 
Statistical Analyses .................................................................................................. 49 
10.5 
Stopping Rule Guidance for Data and Safety Monitoring Board (DSMB) ............... 50 
11 STUDY GOVERNANCE AND OTHER OPERATIONAL CONSIDERATIONS .............................. 51 
11.1 
Sponsor Representative .......................................................................................... 51 
11.2 
Site Selection and Training...................................................................................... 51 
11.3 
Study Central Clinical Eligibility Committee ............................................................ 52 
11.4 
Core Laboratories .................................................................................................... 52 
11.5 
Independent Data Monitor ..................................................................................... 52 
11.6 
Clinical Events Adjudication Committee (CEAC) ..................................................... 53 
11.7 
Data and Safety Monitoring Board (DSMB) ............................................................ 53 
11.8 
Publications Committee .......................................................................................... 53 
11.9 
Publication and Data Sharing Policy ....................................................................... 54 
11.10 
Intellectual Property ............................................................................................... 55 
11.11 
Informed Consent Process ...................................................................................... 55 
11.12 
Unscheduled Study Discontinuation and Closure .................................................. 56 
11.13 
Confidentiality and Privacy ..................................................................................... 57 
11.14 
Future use of Stored Specimens and Data ............................................................. 58 
11.15 
Clinical Monitoring .................................................................................................. 58 
11.16 
Quality Assurance and Quality Control ................................................................... 59 
11.17 
Data Handling and Record Keeping ........................................................................ 60 
11.18 
Study Records Retention ........................................................................................ 61 
11.19 
Collaborative Agreements ...................................................................................... 62 
11.20 
Conflict of Interest Policy ........................................................................................ 62 
12 ABBREVIATIONS ................................................................................................................. 62 
13 APPENDIX A: Sample Case Report Forms .......................................................................... 64 
14 Appendix B: Reporting Obligations .................................................................................... 65 
14.1 
Reporting obligations of NIH Principal Investigator ............................................... 65 
14.2 
Reporting obligations of Enrolling Site Principal Investigator to the Sponsor* ..... 66 
15 VERSIONS ........................................................................................................................... 66 
16 REFERENCES ....................................................................................................................... 68 

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1 
STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP) and the following: United States (US) Code of Federal 
Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 

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2 
PROTOCOL SUMMARY 
2.1 
Synopsis 
Title 
NHLBI Transmural Electrosurgery LeafLet Traversal and Laceration Evaluation 
(TELLTALE) BASILICA-TAVR Trial 
Background / 
Précis 
Transcatheter aortic valve implantation (TAVR) may cause life threatening 
coronary artery obstruction, whether implanted in native aortic stenosis or 
bioprosthetic aortic valve failure. 
We have developed and validated the techniques of BASILICA (Bioprosthetic 
Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery 
obstruction during transcatheter aortic valve replacement), using bedside 
modification of off-the-shelf guidewires. These bedside modifications require 
additional assembly steps and special expertise, and thereby risks procedure 
failure and complications. 
Transmural Systems and NHLBI have developed a purpose-built electrosurgical 
guidewire system (TELLTALE) to simplify the BASILICA-TAVR procedure. The 
purpose of this protocol is to test the efficacy and safety of this purpose-built 
guidewire in the setting of BASILICA-TAVR. 
Risk 
classification 
Significant risk device protocol requiring Investigational Device Exemption 
(IDE)  
Device 
classification 
Class II 
Intended Use 
The TELLTALE Guidewire System is intended for transcatheter electrosurgical 
traversal and laceration of native and bioprosthetic tissue. 
Indications for 
use 
The TELLTALE guidewire is indicated for transcatheter electrosurgical traversal 
and/or laceration of native and bioprosthetic tissue for the applicable 
procedures listed below. 
Applicable traversal and laceration procedures including BASILICA 
(Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic 
Coronary Artery obstruction during transcatheter aortic valve replacement). 
The TELLTALE Guidewire System is available only by physician prescription. 
Design 
overview 
Prospective, multicenter, single arm, open-label, evaluation of the NHLBI 
Transmural TELLTALE Guidewire System 
Study phase 
Not applicable 

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Sponsor / 
Representative 
NHLBI Office of the Clinical Director (NHLBI/OCD) / 
Robert J. Lederman, MD, NHLBI/DIR/CB/LCI 
Study Manager Annette M. Stine, RN 
Hypothesis 
We hypothesize that the TELLTALE guidewire system traverses and lacerates 
intended native and bioprosthetic aortic valve leaflets that threaten coronary 
artery obstruction during TAVR. 
We further hypothesize that BASILICA using the TELLTALE guidewire system 
prevents TAVR-related acute coronary obstruction in patients at risk, and with 
acceptable safety. 
Number of 
subjects 
90 subjects enrolled at up to 15 investigational sites in the US. 
Up to 180 subjects may be screened for participation. 
Sample Size 
Justification 
The sample size is not statistically derived. 
Up to 180 candidates will be screened until 90 subjects undergo attempted 
TELLTALE BASILICA-TAVR in this protocol.  
There is a quota of 30 subjects who must have native TELLTALE BASILICA-TAVR 
of the 90 total enrolled subjects. 
 
Inclusion 
Criteria 
• Adults age ≥ 21 years 
• High or prohibitive risk of surgical aortic valve replacement according to 
the local multidisciplinary heart team 
• Undergoing TAVR for bioprosthetic aortic valve failure or native aortic 
stenosis (“on-label” TAVR) 
• Local multidisciplinary heart team determines subject to be at high risk of 
TAVR-induced coronary artery obstruction 
• Deemed likely to suffer coronary artery obstruction from TAVR based on 
NHLBI Core lab analysis of CT, any of 
• 
Risk is narrow Sinus of Valsalva: (a) Leaflet height is greater than 
coronary artery height, and (b) Virtual transcatheter valve-to-
coronary (VTC) distance < 4mm 
• 
Risk is Sinus sequestration: (a) Threatening leaflet height is greater 
than sinotubular junction, and (b) Virtual transcatheter valve-to-
sinotubular-junction distance (VTS) < 2mm at the affected Sinus 
• Concurrence of the Study Eligibility Committee 
• Able to understand the protocol, consents in writing to participate, and 
willing to comply with all study procedures for the duration of the study 
 

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Exclusion 
Criteria 
• Requires doppio (two-leaflet) BASILICA 
• Flail target leaflet at baseline 
• Excessive target aortic leaflet calcification (no basal calcium-free window 
or potentially obstructive calcific masses) on baseline CT 
• Planned provisional (pre-position coronary artery) stents despite BASILICA 
• Requires non-femoral access 
• Requires concomitant procedures during TAVR (such as percutaneous 
coronary intervention for baseline obstructive coronary artery disease) 
• Chronic kidney disease KDIGO stage 4 or 5 (eGFR < 29 ml/min/1.73m2) or 
renal replacement therapy 
• Not expected to survive for 12 months 
• Pregnant at the time of intended treatment (day 0) 
 
Selection 
quota 
A subset of subjects will have native aortic valve failure (initially n=15). 
Sequential enrollment will accommodate this quota. A "study expansion" IDE 
amendment increased this quota from 15 to a maximum 30.   
 
Primary 
Efficacy 
Endpoint 
The primary efficacy endpoint is Device (technical) success, assessed upon exit 
from the cardiac catheterization laboratory, including all of the following: 
• Successful electrosurgical leaflet traversal using the TELLTALE Guidewire, 
when attempted; and 
• Successful electrosurgical leaflet laceration using the TELLTALE Guidewire; 
and 
• Successful retrieval of the TELLTALE Guidewire System 
 
Primary Safety 
Endpoint 
The primary safety endpoint is Inpatient safety, which is a composite of all of 
following assessed upon discharge from the index hospital admission: 
• (Freedom from) all-cause mortality 
• (Freedom from) stroke, both disabling and non-disabling 
• (Freedom from) acute coronary artery obstruction 
• (Freedom from) emergency cardiac surgery or reintervention related to 
the TELLTALE BASILICA procedure or device 
• (Freedom from) BASILICA-related complications including coronary artery 
perforation, coronary artery dissection, aortic dissection, cardiac free wall 
perforation, or systemic embolization of a native or bioprosthetic leaflet 
 

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Secondary 
endpoints 
The secondary endpoint is 30-day safety, as assessed by freedom from MACE 
(according to VARC-3 [30]) at 30 days, including freedom from all of the 
following: 
• All-cause mortality 
• All stroke (disabling and non-disabling) 
• Bleeding VARC-3 Type 2 or greater (requiring two or more units of 
transfused blood or hemoglobin drop >3g/dL) 
• Major vascular, access-related, or cardiac structural complication 
(according to VARC-3, which includes coronary obstruction) 
• Acute kidney injury stage 3 or 4 
• Moderate or severe aortic regurgitation 
• New permanent pacemaker due to procedure-related conduction 
abnormalities 
• Surgery or intervention related to the TELLTALE device 
 
Exploratory 
endpoints 
• Primary and secondary endpoints among subjects with native versus 
bioprosthetic disease 
• Stroke: disabling and non-disabling 
• Coronary stenting: snorkel (heterotopic) and orthotopic (through TAVR 
stent cells), to prevent or treat leaflet-induced coronary obstruction before 
(preemptive) and after (bailout or cautionary) TAVR. 
• Facilitated BASILICA procedure success, as defined in section 0. 
• Composite safety (secondary endpoint) assessed at 90 days 
• Ability selectively to engage threatened coronary ostia after BASILICA-
TAVR 
• Acute hemodynamic deterioration in the interval between BASILICA and 
TAVR 
• Outcomes of subjects who participate in live case demonstrations 
compared with those who do not  
 

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Study 
Overview 
NHLBI Data Coordinating Center 
Central IRB  
Selected site operators have experience with off-label BASILICA 
Subjects are identified by site investigators 
Baseline CT and procedure fluoroscopy are analyzed by core laboratory 
Subject eligibility is confirmed by institutional multidisciplinary heart team, 
and is confirmed by study eligibility committee 
Subjects are enrolled prospectively 
Stroke assessment by trained and certified staff 
Analyses based on day 0 and day 30 outcomes 
Subjects go “off-study” after [90 days] visit 
Study Duration 12 months for enrollment + follow-up 
Duration of 
Participation 
for Subjects 
90 days 
Enrollment 
Candidates may use screening consent based on local institutional preference. 
Candidates do not sign research informed consent until after they are 
reviewed and invited by the Central Clinical Eligibility Committee. 

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2.2 
Schema 
TAVR planned for 
native or bioprosthetic 
aortic valve failure
High risk of coronary 
artery obstruction 
from TAVR
Central eligibility 
review
Informed Consent and 
Baseline assessment
Pre-discharge safety 
assessment
TELLTALE-BASILICA 
followed by TAVR
30-day assessment 
in-person
90-day assessment 
remote or in-person
 
Figure 1. Protocol Schema 

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2.3 
Schedule of Activities (SOA) 
 
Screening 
 (± 6 mo) 
Baseline 
 (± 6 wk) 
Day 0 
(procedure) 
Inpatient 
30 d (±3wk) 
90-day 
(± 3 wk) 
Baseline informed consent 
 
X 
 
 
 
 
Multidisciplinary heart team eligibility determination 
X 
 
 
 
 
 
Clinical study eligibility committee concurrence (*) 
X 
 
 
 
 
 
Clinical in-person assessment including vital signs  
 
X 
 
X 
X 
 
Clinical remote or in-person assessment 
 
 
 
 
 
X 
NYHA Classification 
 
X 
 
 
X 
 
Kansas City Cardiomyopathy Questionnaire (KCCQ-23) (*) 
 
X 
 
 
X 
 
NIH Stroke Scale (Severity) Assessment (*) 
 
X 
 
X 
X 
 
Modified Rankin Stroke Disability Score (*) 
 
X 
 
X 
X 
 
Frailty tests: Katz ADL, 5MW, Albumin  
 
X 
 
 
 
 
Blood test for pregnancy (hCG) if premenopausal woman 
 
X 
 
 
 
 
Blood tests: CBC, Platelet, Chemistry Panel 
 
X 
 
X 
X 
 
Blood test: Troponin I  
 
X 
Post-
procedure 
# 
 
ECG  
 
X 
X 
X 
X 
 
Cardiac CT contrast-enhanced ECG-gated  
(up to 6 months before procedure recommended ¤) 
Screening or 
baseline 
Screening or 
baseline 
 
 
 
 
Coronary arteriography§  
Screening or 
baseline 
Screening or 
baseline 
X 
 
 
 
BASILICA using TELLTALE (*) followed by TAVR  
 
 
X 
 
 
 
Echocardiogram, surface or transesophageal 
Screening or 
baseline 
Screening or 
baseline 
X 
X 
X 
 
Adverse event assessment (*) 
 
 
X 
X 
X 
X 
(*) denotes research activity. (#) denotes obtain if abnormal at discharge 
(§)coronary arteriograms are obtained only as clinically indicated and, only if obtained, will be analyzed at NIH for research 
(¤) CT scans beyond the 6-month recommended window if the treating physician would proceed with BASILICA TAVR without an updated CT 
scan if outside the TELLTALE protocol 

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2.4 
Blood tests 
All of the blood tests specified here are mandatory for routine medical care before, during, and after the 
TAVR procedure. The results are recorded as research values and in surveillance for adverse events. No 
other blood tests are reported as adverse events. 
The specific blood tests are enumerated below, and reported as study adverse events only if they  meet 
the criteria for a serious adverse event (SAE), serious adverse device effect (SADE), unanticipated 
adverse device effect (UUADE) or an unanticipated problem (UP) as described below: 
Test 
Detail 
Inpatient 
value to 
record 
Timepoints to 
collect 
Criteria for reporting as serious 
AE or serious ADE 
Blood count: 
hemoglobin 
Marker of anemia and 
hemodilution. 
Lowest 
Baseline through 
30d 
Decrease in conjunction with a 
VARC-3 major or minor  
- Access site complication 
- Cardiac structural complication  
- Bleeding complication 
that requires prolonged 
hospitalization, unplanned 
surgical or interventional 
treatment or a blood or platelet 
transfusion 
Blood count: 
hematocrit 
Marker of anemia and 
hemodilution. 
Lowest 
Baseline through 
30d 
Blood count: platelet 
Nonspecific marker of 
coagulation and of 
inflammation. 
Lowest 
Baseline through 
30d 
Blood count: white 
blood cell count 
Nonspecific marker of 
inflammation and infection. 
Highest 
Baseline through 
30d 
Elevation in conjunction with 
suspected clinical infection or 
inflammation and requiring 
treatment 
Chemistry: Creatinine  Marker of renal excretion. eGFR  Highest 
Baseline through 
30d 
Classified as VARC-3 acute kidney 
injury (AKI) grade 3 or higher and 
requires treatment 
Chemistry: Estimated 
glomerular filtration 
rate (eGFR) 
Calculated from age, sex, race, 
and creatinine 
Lowest 
Baseline through 
30d 
Chemistry: Cardiac 
troponin 
Marker of cardiomyocyte injury, 
institution-specific subtype 
(Troponin-I or Troponin-T). 
Highest 
Baseline & 
postprocedure. 30-
day if abnormal at 
discharge 
Elevated in association with 
symptoms and signs of acute 
myocardial infarction including 
ECG and/or imaging 
 
2.5 
Clinical versus research activities 
All activities except Consent, TELLTALE BASILICA-TAVR, KCCQ-23, NIH Stroke Scale Assessment, 
Modified Rankin Score, and Adverse event assessment are performed for standard clinical care. 
 
 

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3 
INTRODUCTION 
3.1 
Public précis 
Transcatheter aortic valve replacement (TAVR) is a lifesaving treatment option for many 
patients with symptomatic severe aortic stenosis or failure of a surgically-implanted 
bioprosthetic valve. Rarely, TAVR can block blood flow to the coronary arteries, which supply 
blood to the heart, by displacing the leaflets of the prior valve outwards. TAVR-associated 
coronary artery obstruction is associated with up to 50% death rate. 
BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic 
Coronary Artery obstruction) is a procedure developed to prevent coronary artery obstruction 
by cutting the threatening leaflet immediately before TAVR. The NHLBI TELLTALE study 
investigates the use of a dedicated electrosurgical guidewire system to perform BASILICA and 
tests the safety and effectiveness of using this device in patients at risk of coronary artery 
obstruction from TAVR.  
3.2 
Background and Clinical Justification 
Study Rationale 
Coronary artery obstruction is a rare complication of transcatheter aortic valve replacement 
(TAVR) but is associated with an inpatient mortality of up to 50%[1]. Coronary artery 
obstruction occurs when the diseased native or bioprosthetic valve leaflets obstruct blood flow 
at the coronary ostia or sinotubular junction and can be predicted on pre-procedure CT[1, 2]. 
BASILICA prevents coronary artery obstruction by lacerating the culprit leaflet immediately 
before TAVR[3].  
BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic 
Coronary Artery obstruction) is currently performed using off-the-shelf commercial equipment 
(“off label”). This adds complexity and potentially unpredictability to the procedure. The 
TELLTALE Guidewire System by Transmural Systems is a dedicated guidewire for transcatheter 
electrosurgical traversal and laceration of valve leaflets. The NHLBI TELLTALE Study investigates 
the use of this novel guidewire in performing BASILICA safely and effectively to prevent 
coronary obstruction in at-risk patients undergoing TAVR.  
The BASILICA procedure has been shown to be feasible, safe and effective at preventing 
coronary obstruction in at risk patients undergoing TAVR in an IDE study[3] and large 
multicenter registry[4]. However, the procedure uses off-the-shelf equipment off-label. This 
adds complexity (Figure 2) and potential for complications. In our unpublished experience, the 
complexity includes the temptation to avoid dextrose flooding during laceration (see below), 
with its attendant risk for leaflet mechanical avulsion. Furthermore, the self-assembled co-axial 
systems currently used may divert physicians to apply the much less attractive, though simpler, 
bail-out procedure of snorkel stenting, with its attendant complications of stent under-
expansion, thrombosis, delayed coronary obstruction, loss of future coronary access and long 
term dual antiplatelet therapy. The TELLTALE Guidewire System is purpose-designed for 
electrosurgical traversal and laceration of leaflets. This study tests whether the TELLTALE 

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Guidewire System can be used to successfully perform BASILICA to safely and effectively 
prevent coronary artery obstruction from TAVR in at risk patients.  
 
Figure 2.Complicated  set-up for BASILICA using bedside-modified devices, from [5]. 
Transcatheter electrosurgery 
Transcatheter electrosurgery is a technique to vaporize tissue using radiofrequency alternating 
current directed through guidewires and catheters and concentrated in the tissue to cause 
rapid heating. Cells vaporize when intracellular temperatures reach 100 degrees C. This 
technique has been used for “traversal”, for example in recanalizing occlusive lesions and 
crossing cardiovascular chambers, and for “laceration”, for example in cutting aortic and mitral 
leaflets to prevent blood flow obstruction from transcatheter valve replacement.  
Electrosurgery relies on tissue conducting alternating current between two electrodes. High 
frequency alternating currents (~500KHz, or ‘radiofrequency’) do not stimulate nerve and 
muscle tissue and thus avoid pain, muscle contraction, and myocardial fibrillation [6]. 
We previously performed current density simulations using the AC/DC module on Comsol 
Multiphysics (Comsol Inc. MA,USA) simulation software to find the optimal configuration for 
guidewire insulation for traversal and laceration (Figure 3)[7]. The biological structures were 
represented as simplified geometries. A 100W power source was used with 100V and 1A 
voltage and current outputs at 700kHz to simulate commercially available electrosurgery units. 
The conductivity and the relative permittivity values for blood, leaflet, myocardium, dextrose 
and PTFE were derived from published literature[8-10].   

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Figure 3. Simulated traversal (top) and laceration systems (A-E) depicting the value of focused current and displacement of 
conductive fluid. From [7]. 
These simulations were replicated on the benchtop (Figure 4). These experiments highlight the 
importance of inner curvature charge concentration via selective denudation, and of robust 
insulation with both microcatheters and non-ionic fluid, to concentrate charge for tissue 
laceration[7].  
Failure to recapitulate these benchtop-derived observations during standard clinical BASILICA 
risks failure and complications. 
 
Figure 4. Benchtop validation of the electrosurgical laceration, from [7] 

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Clinical applications for transcatheter electrosurgery 
The table below summarizes some of the clinical applications for transcatheter electrosurgery 
[7]. 
Application 
References 
Study type 
Total 
patients 
Procedure 
success 
Complications 
Pulmonary valve 
atresia traversal in 
newborns 
Veldtman 2004 [11] Case series 
136 
87% successful 
in establishing 
antegrade flow 
Procedural death 
(7%); Arrhythmia, 
RVOT perforation 
(16%) 
Central chronic total 
venous occlusion 
traversal (subclavian 
vein, SVC) 
Baerlocher 2006; 
Iafrati 2012; Foerst 
2017 [12-14] 
Case reports 
6 
100% 
None reported 
Coronary chronic total 
occlusion 
Baim 2004 [15] 
Prospective 
multicenter 
registry 
116 
54% 
Perforation and 
tamponade (2.6%) 
Transseptal puncture Hsu 2013 [16] 
Randomized 
control trial 
36 RF;  
36 
conventional 
100% RF; 72% 
conventional 
(with cross-over 
to RF and 
subsequent 
success) 
Pericardial effusion 
(2.8%) 
Interventricular 
septum puncture (for 
LV lead placement) 
Gamble 2018 [17] 
Prospective 
single center 
single arm 
clinical trial 
20 
100% success in 
ventricular 
traversal 
Disabling stroke (5%) 
Transcaval for large 
bore access for TAVR 
Greenbaum 
2017[18] 
Lederman 2019[19] 
Costa 2019[20] 
Prospective 
multicenter 
single arm 
clinical trial 
Retrospective 
registry 
150 
99% 
Life-threatening or 
disabling bleeding (4-
12%) 
Note late 
complications 
LAMPOON to lacerate 
the anterior mitral 
valve leaflet prior to 
TMVR 
Khan 2019 [21] 
Prospective 
multicenter 
single arm 
clinical trial 
30 
100% 
More than mild 
paravalvular leak 
(23%); LVOT 
obstruction from 
valve skirt (10%).  
BASILICA to lacerate 
aortic leaflets prior to 
TAVR 
Khan 2019 [3] 
Prospective 
multicenter 
single arm 
clinical trial 
30 
93% 
Disabling stroke (3%) 
ELASTIC to enable 
TMVR after mitral 
edge-to-edge repair 
Lisko 2020 [22] 
Retrospective 
case series 
5 
100% 
Moderate 
paravalvular leak 
(40%) 
 

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BASILICA using bedside modification of commercial devices (“off-label”) 
The BASILICA procedure was developed in pigs and subsequently performed in a compassionate 
basis in seven patients[23]. All patients had successful TAVR, with no coronary obstruction, 
stroke, hemodynamic compromise or any major complications. All patients survived to 30 days.  
The prospective FDA IDE NHLBI BASILICA study enrolled 30 patients at high risk of coronary 
artery obstruction from TAVR who underwent BASILICA with an Astato guidewire with 
benchtop modification[3]. All patients were at high risk of coronary obstruction as determined 
by the NHLBI CT core laboratory. Seven (23%) were double-leaflet BASILICA.  Primary success of 
successful BASILICA and TAVR without coronary obstruction or reintervention was met in 28 
(93%) subjects. BASILICA traversal and laceration was successful in 28 (93%) subjects. There was 
100% freedom from coronary obstruction and reintervention. Primary safety of freedom from 
MACE was met in 21 (70%), driven by six (20%) major vascular complications related to TAVR 
but not BASILICA. There was one death at 30 days. There was one (3%) disabling stroke and two 
(7%) non-disabling strokes. Transient hemodynamic compromise was rare (7%) and resolved 
promptly with TAVR. At one year, there were no late complications associated with 
BASILICA[24]. Specifically, after 30 days there was no stroke, myocardial infarction, coronary 
intervention, transcatheter aortic valve failure or increase in valve gradients. The coronaries 
remained clinically patent and there were no BASILICA related deaths. 
The international multicenter BASILICA Registry reported results on 214 patients undergoing 
BASILICA and TAVR in patients at high risk of coronary artery obstruction[4]. 22% were doppio 
(double-leaflet) BASILICA. Procedural success, a composite of successful traversal and 
laceration, survival and freedom from coronary obstruction or re-intervention was seen in 87%. 
The 30-day mortality was 2.8% and stroke rate 2.8% (0.5% disabling stroke).  
The EURO-BASILICA multicenter registry reported 76 patients at 10 centers undergoing 
BASILICA and TAVR in patients at high risk of coronary artery obstruction, using commercial off-
the-shelf devices [25].  Nine (12%) were doppio (double-leaflet) BASILICA. Technical success was 
98%, freedom from coronary obstruction was 91%, stroke was 3%. Ten patients required 
coronary intervention, typically because of avulsed or prolapsed leaflets amenable to 
orthotopic stenting. 
An interim analysis of this open-label study for amendment B (September 2023) was triggered 
by consent of 15 subjects with native aortic valve failure. At this timepoint 27 subjects were 
treated by TELLTALE BASILICA TAVR, including 14 with native aortic valve failure. Using non-
adjudicated data, the primary success rate is 100%, the incidence of coronary obstruction is 0%, 
and the incidence of stroke/TIA is 0%. Based on these data we propose amending the protocol 
in Amendment B to expand the study cohort having native aortic valve failure, from 15 to 30 
subjects. 
These studies provide reassuring data in support of the BASILICA procedure to prevent coronary 
artery obstruction in this patient cohort with few good options.  

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Available literature about risks of coronary obstruction 
Reported and expected outcomes of patients undergoing TAVR despite risk of coronary 
obstruction 
Setting n with CTs 
evaluated 
At-risk population Cor obstruction in 
at-risk population 
30-day Death 
Stroke Reference 
ViV 
20 
obstructed,  
90 control 
VTC<4mm 
89% 
53% (in obstructed 
population) 
0% 
VIVID registry 
[2] 
Native 
AS 
28 
obstructed,  
345 control 
coronary 
height<12mm and 
SOV width <30mm 
87% 
41% (in obstructed 
population) 
9% 
Multicenter 
Registry [1] 
Native 
AS 
60 
obstructed,  
60 control 
Leaflet height ≥ 
coronary height 
AND VTC<4mm 
90% 
27% (in-hospital death, 
obstructed) 
Not 
collected 
CRT 2020 late 
breaking trial 
presentation, 
not published 
VIV and 
Native 
30 
attempted 
BASILICA 
Leaflet height ≥ 
coronary height 
AND VTC<4mm; 
Leaflet height ≥ STJ 
AND VTSTJ<2mm 
0% 
3% 
10% 
[3] 
VIV and 
Native 
214 
attempted 
BASILICA 
Leaflet height ≥ 
coronary height 
AND VTC<4mm; 
Leaflet height ≥ STJ 
AND VTSTJ<2mm 
5% 
3% 
3% 
[4] 
VIV and 
Native 
15 
attempted 
BASILICA 
Leaflet height ≥ 
coronary height 
AND VTC<4mm; 
Leaflet height ≥ STJ 
AND VTSTJ<2mm 
7% 
0% 
0% 
[26] 
VIV and 
Native 
21 
attempted 
BASILICA 
Leaflet height ≥ 
coronary height 
AND VTC<4mm; 
Leaflet height ≥ STJ 
AND VTSTJ<2mm 
5% 
0% 
0% 
[27] 

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Compared with pivotal trials in which all candidates at risk of coronary obstruction are 
EXCLUDED 
Setting Population 
n 
Cor 
obstruction 
30-day 
Death 
Stroke  
Native 
AS 
Excluded “Bulky calcified aortic valve leaflets in 
close proximity to coronary ostia” 
348 
0% 
3.4% 
3.8% PARTNER 1 
Native 
AS 
Excluded “Bulky calcified aortic valve leaflets in 
close proximity to coronary ostia” 
1011 
0.4% 
3.9% 
5.5% PARTNER 2 
Native 
AS 
Excluded “Bulky calcified aortic valve leaflets in 
close proximity to coronary ostia” 
496 
0.2% 
0.4% 
0.6% PARTNER 3 
Native 
AS 
Excluded “Sinus of Valsalva anatomy that would 
prevent adequate coronary perfusion.” 
390 
0.6% 
3.3% 
4.9% CoreValve 
Native 
AS 
Excluded “Sinus of Valsalva anatomy that would 
prevent adequate coronary perfusion.” 
879 
? 
2.2% 
4.5% SURTAVI 
Native 
AS 
Excluded “Sinus of Valsalva anatomy that would 
prevent adequate coronary perfusion.” 
734 
0.9% 
0.5% 
3.4% Evolut Low 
Risk 
 
Weighted average of subjects selected to be at low 
risk of coronary obstruction 
3858 
0.5% 
2.3% 
4.0%  
Bioprosthetic versus native mortality and stroke after BASILICA 
 Publication 
Setting 
Coronary Obstruction 
Death 
All Stroke 
Registry [4] 
  
Bioprosthetic (n=155) 
7 (4.5%) 
3% 
3% 
Native (n=58) 
3 (5.2%) 
2% 
2% 
Adjudicated NHLBI [3] 
  
Bioprosthetic (n=17) 
0 
1 (6%) 
2 (12%) 
Native (n=13) 
0 
0 (0%) 
1 (10%) 
Based on the above: 
 
Coronary Obstruction 
30-day Death 
Stroke 
Expected without BASILICA 
90% 
40% 
5% 
Expected after TELLTALE BASILICA 
5% 
3% 
5% 
 

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Complications of BASILICA using bedside modification of commercial devices (“off-label”) 
Bleeding 
Some blood loss is typical during BASILICA using off-label equipment through the multiple co-
axial systems. These are mainly related to access-site bleeding and to procedural blood 
wastage.  
Inability to traverse 
This is the commonest reason for procedure failure, and often due to incorrect equipment 
setup, inability to get orthogonal to the target leaflet using geometrically-unsuitable 
commercially available catheters, inadequate electrical charge concentration because of 
difficulty deploying optimal insulation around the traversal guidewire, and extensive leaflet 
calcification including at the leaflet nadir.  
We expect this complication to be mitigated by using a purpose-built device. 
Incorrect (non-target) traversal 
Misdirected guidewires may traverse into the left atrium or interventricular septum or anterior 
mitral valve leaflet. These are often easily recognized on TEE or by inability to snare the 
guidewire in the LVOT. The guidewire is withdrawn and re-directed, typically without adverse 
effect.  
We expect this complication to be reduced by using dedicated-shape guiding catheters. 
Mechanical laceration and leaflet avulsion 
If there is insufficient charge concentration on the leaflet during laceration, for example when 
dextrose flush is not used or inner surface denudation is not effectively performed, then the 
leaflet may avulse through excessive mechanical force. This can cause serious  hemodynamic 
compromise and risk leaflet prolapse into the coronary arteries. This can be avoided with 
effective insulation and avoiding excessive mechanical force.  
We expect this complication to be mitigated by using a purpose-built device. 
Mitral apparatus damage 
If the guidewire is snared below the level of the LVOT, there is risk of mitral chord 
entanglement and subsequent laceration leading to severe mitral regurgitation. This 
complication can be avoided by only snaring the guidewire in the LVOT.   
Conventional Treatment Options and Alternatives 
Current options for prevention of TAVR-related coronary obstruction include conservative 
management (essentially palliative care in patients with symptomatic severe aortic stenosis or 
bioprosthetic valve failure), surgical aortic valve replacement, snorkel stenting, or BASILICA 
using off-the-shelf equipment off-label. 

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While surgical aortic valve replacement is an excellent option for some patients, many are at 
high risk of mortality or morbidity from surgery, often including patients undergoing redo 
procedures for failing bioprosthetic valves. Many patients demur when offered surgery and 
insist on a transcatheter alternative. 
Snorkel stenting is not a preventative measure but is a bail-out procedure with risks of stent 
compression, stent under-expansion, thrombosis, loss of coronary access and long term dual 
antiplatelet therapy. 
BASILICA directly addresses the pathophysiology of coronary obstruction but there are no 
dedicated devices at present to democratize this procedure. 
3.3 
Risk/Benefit Assessment 
Known Potential Risks (Anticipated Adverse Device Effects) 
TELLTALE/BASILICA-specific complications 
- 
Embolization of air, valve debris, atheroma, or thrombus/clot to coronary, cerebral, 
visceral, or systemic circulation possibly causing symptomatic ischemia/infarction 
- 
Myocardial ischemia or infarction (acute coronary syndrome or heart attack) 
- 
Aortic regurgitation after laceration before TAVR, possibly causing hypotension or 
cardiogenic shock 
- 
Avulsion or other injury of the native or prosthetic aortic valve leaflet, including leaflet 
prolapse into the coronary arteries, and including embolism of the leaflet into the 
coronary, cerebral, visceral, or other systemic arteries 
- 
Inadvertent injury of the mitral valve apparatus requiring transcatheter or surgical 
repair 
- 
Traversal into the left atrium or other non-target chamber 
- 
Electrical coupling of TELLTALE guidewire and (a) bioprosthetic valve frame, (b) guiding 
catheters, (c) guidewires and snares causing heating, thromboembolism, 
tachyarrhythmia, and electrosurgery failure 
- 
Native coronary artery injury from mechanical or electrosurgery injury requiring 
percutaneous catheter or surgical treatment 
- 
Other arterial perforation or injury or dissection, including requiring surgical treatment 
- 
Failure to engage the intended native or bioprosthetic aortic valve leaflet with TELLTALE 
system to initiate traversal at the intended location 
- 
Mechanical failure of the TELLTALE Guidewire System including fracture and 
embolization of the guidewire or of the delivery catheters 
- 
Stroke or transient ischemic attack or paralysis 
- 
Permanent disability 
- 
Death 

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General complications of TAVR and BASILICA-TAVR catheter procedure including TELLTALE 
system 
- 
BASILICA failure: Failure to prevent coronary obstruction and acute myocardial ischemia 
requiring transcatheter therapy including percutaneous coronary stenting in a 
heterotopic (“snorkel”) or orthotopic (through TAVR struts) position, or requiring 
emergency cardiac surgery repair 
- 
BASILICA failure: coronary obstruction caused by the malorientation of struts of TAVR 
device, or by fabric skirt of TAVR device, despite successful leaflet laceration 
- 
Hypotension or shock or cardiopulmonary arrest including requiring cardiopulmonary 
resuscitation, chest compressions, cardioversion/defibrillation, vasoactive medications, 
and/or mechanical circulatory support and/or extracorporeal membrane oxygenation 
- 
Complications of percutaneous venous and/or arterial access including bleeding, 
retroperitoneal hematoma, local hematoma, perforation, fistula, pseudoaneurysm, 
compartment syndrome, peripheral nerve injury, chronic pain, infection, among other 
things 
- 
Acute kidney injury related to BASILICA requiring temporary or permanent hemodialysis 
or other medical treatment 
- 
Congestive heart failure, elevated natriuretic peptides, or cardiogenic shock that may 
require intervention 
- 
Volume overload, pleural effusion, pulmonary edema, dyspnea, edema, pericardial 
effusion, or other congestion from procedure-related volume perturbations or other 
heart failure 
- 
Respiratory failure requiring oxygen therapy, mechanical support or mechanical 
ventilation 
- 
Transcatheter heart valve failure including hypo-attenuated leaflet thickening (HALT), 
reduced leaflet motion, valvular regurgitation, valvular stenosis, prosthetic valve 
endocarditis, paravalvular leak, structural deterioration, or non-structural valve 
dysfunction, and/or murmur 
- 
Infection including device infection, endocarditis, infection of a blood vessel 
- 
Infection or sepsis including access sites, lung, urinary tract, or other system 
- 
Abnormal blood tests including serum chemistry tests (creatinine, troponin), electrolyte 
imbalance, and including hematology tests (hemoglobin, hematocrit, platelets, white 
blood cells) 
- 
Hemorrhage requiring transfusion or intervention 
- 
Hemolysis related to blood flow around the lacerated aortic leaflets 
- 
Pain including chest pain, angina, back pain, access site pain, neuropathy, and 
generalized pain 
- 
Pericardial effusion or tamponade requiring percutaneous or surgical treatment 
- 
Pneumothorax, hydrothorax, and hemothorax 
- 
Cardiac arrhythmia including atrial fibrillation, atrial flutter, ventricular tachycardia, 
ventricular fibrillation including cardiac arrest requiring cardioversion/defibrillation or 
cardiopulmonary resuscitation 

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- 
Conduction system defect which may require a temporary or permanent pacemaker, for 
example high-degree atrioventricular block or His-Purkinje block 
- 
Syncope, pre-syncope, seizure, delirium, or other loss of consciousness 
- 
Other venous thrombosis or thromboembolism including deep vein thrombosis, and 
pulmonary thromboembolism 
- 
Radiation injury including intractable skin injury 
- 
High blood pressure 
Allergic or inflammatory reaction to 
- 
anesthesia, 
- 
contrast media, 
- 
materials in the TELLTALE Guidewire System 
The Sponsor and investigators recognize these risks are high and reflect the underlying 
comorbidities, yet consider procedural risks overall to be an acceptable compromise to enable 
TAVR in patients otherwise ineligible. 
Risks related to Radiation 
In this research protocol, subjects will be exposed to incremental radiation fluoroscopy to add 
the BASILICA procedure using the TELLTALE system to conventional TAVR. It is estimated 
(conservatively) that the amount of research radiation that a subject will be exposed to during 
participation in this research protocol will be approximately 30mSv from approximately 30 
minutes of fluoroscopy during performance of BASILICA-TAVR using TELLTALE. This is equivalent 
to 750 chest X-rays.  
We believe the total fluoroscopy exposure to be justifiable in this setting, given the seriousness 
of their cardiovascular disease and limited options. We estimate the benefit to the research 
subjects for these procedures to outweigh the risks. 
Risks to privacy: Personal Identifiable Information 
Clinical data from subjects participating in this trial will retain personally identifiable 
information. This includes CT scans, echocardiograms, and medical records. 
Abstracted data will be coded (personally identifiable information removed but linking codes 
retained) and for transmission to participating subcontracting investigators, clinical events 
adjudication committee, statistician, and to Transmural Systems which is the collaborating 
manufacturer of the TELLTALE system. 
DICOM data will be stored in a secured NIH research PACS system for analysis, including 
personally identifiable information. 
Known Potential Benefits 
Subjects are expected to benefit from investigational BASILICA using the TELLTALE purpose-
built leaflet traversal and laceration system. TELLTALE BASILICA-TAVR is expected to be non-
inferior to bedside-modified and off-label use of devices for electrosurgical traversal and 

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laceration for BASILICA to prevent acute and subacute coronary obstruction from TAVR. 
BASILICA is believed to enable TAVR not otherwise possible without “snorkel stenting,” which 
many physicians believe to be unsafe. 
Subjects may also benefit indirectly from increased medical attention from participating in an 
early feasibility study. 
Future patients, and therefore society, may benefit should the TELLTALE system prove safe and 
effective. 
Alternatives to research participation 
Candidates for TAVR with BASILICA have no good treatment alternatives. They are not eligible 
for surgical aortic valve replacement because of high or prohibitive risk of perioperative death 
or serious morbidity. They are not candidates for conventional TAVR, which risks life-
threatening coronary obstruction. TAVR using pre-positioned coronary stents (“snorkel-stents”) 
risks early and late catastrophic stent failure and coronary obstruction, which has high 
mortality[28, 29].  
Candidates for TAVR with BASILICA who do not consent to participate in this study are eligible 
for “standard” BASILICA using off-label medical devices, including bedside modification of 
commercial devices. This approach, developed by the investigators of this trial, has become the 
“best practice.”  Such off-label BASILICA is likely inferior to the research intervention using the 
TELLTALE guidewire system because of risk of thromboembolism from inferior electrical 
performance of bedside-modified devices, risks of device fracture or other failure from inferior 
mechanical performance of bedside-modified devices, risks of mal-preparation during bedside 
modification including asymmetric denudation, risks of mal-positioning of the lacerating surface 
in bedside-modified devices, among others. The study devices, which are purpose-built to 
address these risks, are considered intrinsically superior to bedside-modified devices used off-
label. 
Assessment of Potential Risks and Benefits 
These subjects have few or no good therapeutic alternatives to BASILICA-TAVR and have the 
potential to benefit from this procedure. 
Risk of investigational BASILICA-TAVR using the TELLTALE system is mitigated by including highly 
capable and experienced operators and highly experienced medical centers. The TELLTALE 
system device will be used only by interventional cardiologists who have specific expertise in 
BASILICA and TAVR. 
Overall, the potential benefits of participation appear to exceed the risks to the subjects. 
4 
OBJECTIVES AND ENDPOINTS 
4.1 
Objective 
The objective of this protocol is to test the safety and effectiveness of the TELLTALE guidewire 
system in accomplishing BASILICA leaflet traversal and laceration to prevent coronary artery 
obstruction in patients whose native or bioprosthetic TAVR threatens coronary artery 
obstruction because of narrow sinus of Valsalva and/or sinotubular junction. 

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An additional objective is added in Amendment B, to offer study expansion to the 
investigational BASILICA-TAVR using the TELLTALE system for patients with native aortic valve 
failure at risk of coronary obstruction and who otherwise meet the selection criteria. 
4.2 
Hypotheses 
We hypothesize that the TELLTALE guidewire system traverses and lacerates intended native 
and bioprosthetic aortic valve leaflets that threaten coronary artery obstruction during TAVR. 
We further hypothesize that BASILICA using the TELLTALE guidewire system prevents TAVR-
related acute coronary obstruction in patients at risk, and with acceptable safety. 
4.3 
Endpoint Design Considerations 
The intent of this protocol is to demonstrate safety and efficacy of BASILICA-TAVR using the 
TELLTALE guidewire system to mitigate the risk of TAVR-induced coronary obstruction in at-risk 
patients. The primary endpoint is selected based on the clinical characteristics and implications 
of BASILICA success and failure, which are described below. 
Definitions of BASILICA Success 
BASILICA technical success” in lacerating a leaflet requires successful traversal and successful 
leaflet laceration only. 
“BASILICA procedure success” in preventing coronary obstruction requires successful leaflet 
traversal and laceration and further requires post-TAVR leaflet splay to preserve coronary 
artery blood flow.  Some causes of BASILICA procedure failure despite BASILICA technical 
success include  
(1) THV malrotation causing coronary obstruction by the THV struts; 
(2) BASILICA slice malorientation with regard to the ostium of the threatened coronary 
ostium combined with very small valve-to-coronary distance (VTC); and  
(3) protrusion of aortic leaflet material into the coronary artery after BASILICA and 
TAVR, either because of bulky leaflet calcification or because of mechanical avulsion 
rather than electrosurgical BASILICA laceration. 
“Facilitated BASILICA procedure success” includes immediate orthotopic coronary stenting to 
mitigate aortic leaflet protrusion and protect flow to the threatened coronary artery without 
“snorkel” stenting between the THV and the sinotubular junction. Orthotopic stenting is not 
possible without BASILICA leaflet laceration. Facilitated BASILICA procedure success is 
considered clinically acceptable. Sometimes orthotopic-stent-facilitated BASILICA can mitigate 
THV- or slice- malorientation and preserve coronary flow. While clinically a success, “facilitated 
BASILICA procedure success” is nevertheless classified as failure in this protocol. 
Immediate consequences of BASILICA Failure 
Unsuccessful traversal precludes BASILICA. Typically there are no sequelae to failed traversal 
per se.  The subject continues to risk coronary obstruction as a consequence of TAVR. 
Given successful traversal, the outcomes after attempted laceration are: 

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(1) Successful electrosurgical laceration of the native or bioprosthetic leaflet that threatens 
coronary obstruction after TAVR. Typically there is no immediate hemodynamic 
compromise after electrosurgical leaflet laceration because appropriately split leaflets 
continue to coapt and the result is a mild increment in acute aortic regurgitation. After 
this BASILICA technical success, the results of TAVR will determine BASILICA procedure 
success as described previously; OR 
(2) Unsuccessful electrosurgical laceration but successful mechanical laceration or avulsion. 
This is clinically manifest by a significant increment in aortic regurgitation and 
hemodynamic compromise requiring expedited TAVR. Acute coronary occlusion is 
typically averted, but orthotopic coronary artery stenting is sometimes required 
because the avulsed leaflet may prolapse into the target coronary artery ostium. With 
appropriate operator training, there are typically few sequelae other than orthotopic 
stenting of a non-atherosclerotic ostial coronary artery.  We believe orthotopic stenting 
is safer than heterotopic (“snorkel”) stenting in which a stent extends far proximal to 
the coronary ostium and risks mechanical crush by the transcatheter heart valve against 
the sinotubular junction.  Despite these undesirable characteristics, mechanical avulsion 
can be classified as BASILICA technical success according to our definition; OR 
(3) Aborted or abandoned laceration. Typically there are no sequelae. 
BASILICA is considered failed after unsuccessful traversal or after aborted/abandoned 
laceration.  BASILICA may be successful (clinically) after orthotopic stenting, but in this protocol 
such procedures are classified as unsuccessful investigational BASILICA. 
Alternatives to BASILICA, and remaining options after failed BASILICA 
Remaining options for the patient after failed BASILICA includes: 
(1) Aborting the TAVR procedure with further consideration for surgical aortic valve 
replacement despite predicted high or prohibitive risk of death or severe morbidity; OR 
(2) Proceed with TAVR using snorkel stenting (that the study investigators consider 
inadequate); OR 
(3) Conservative management or hospice; OR 
(4) A repeat attempt at BASILICA during the same, or during a different catheterization 
procedure. 
Implications for trial design 
Patients requiring TAVR who are at risk of TAVR-induced coronary obstruction and who are at 
high or prohibitive risk of surgical aortic valve obstruction have few satisfactory clinical options. 
Increasing these options beyond zero is desirable.  
As described above, BASILICA technical failure typically has no sequelae, and returns patients to 
their baseline state of high spontaneous risk of adverse outcomes. 
Based on our investigational and registry experience with BASILICA using bedside-modified 
commercial devices off-label, there is no evidence of post-discharge complications of 
BASILICA[3, 4, 24].  

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Subjects in this trial have an approximately 90% likelihood of acute coronary obstruction after 
TAVR without BASILICA, and if obstructed, an approximately 40% 30-day mortality. The primary 
endpoint for this trial captures both technical and clinical safety events, and therefore is 
appropriate to characterize the safety and efficacy of BASILICA-TAVR using the TELLTALE 
guidewire system. 
4.4 
Primary Efficacy Endpoint 
The primary efficacy endpoint is Device (technical) success, assessed upon exit from the cardiac 
catheterization laboratory, including all of the following: 
• Successful electrosurgical leaflet traversal using the TELLTALE Guidewire, when attempted; 
and 
• Successful electrosurgical leaflet laceration using the TELLTALE Guidewire; and 
• Successful retrieval of the TELLTALE Guidewire System 
Successful traversal is defined as guidewire traversal from the aortic root across the intended 
aortic leaflet into the left ventricular outflow tract confirmed by either by angiography or by 
leaflet traction upon guidewire ensnarement.  
Successful laceration is defined as intact liberation of the TELLTALE guidewire loop across a 
leaflet, with restoration of guidewire mobility allowing removal from the body. It may be 
confirmed by transesophageal echocardiography. 
Successful retrieval of the TELLTALE guidewire is defined as successful removal from the body 
of an intact TELLTALE guidewire after successful laceration. 
Rationale for primary efficacy endpoint 
The primary efficacy endpoint tests the efficacy of the TELLTALE guidewire, which according to 
the Instructions for Use (IFU) is “…indicated for transcatheter electrosurgical traversal and 
laceration of native and bioprosthetic tissue.” 
This endpoint tests only the efficacy of the TELLTALE guidewire, not of the BASILICA procedure 
nor of the TAVR procedure. Safety endpoints are tested in a separate primary safety endpoint. 
4.5 
Primary Safety Endpoint 
The primary safety endpoint is Inpatient safety, which is a composite of all of following 
assessed upon discharge from the index hospital admission: 
• (Freedom from) all-cause mortality 
• (Freedom from) stroke, both disabling and non-disabling 
• (Freedom from) acute coronary artery obstruction 
• (Freedom from) emergency cardiac surgery or reintervention related to the TELLTALE 
BASILICA procedure or device 
• (Freedom from) BASILICA-related complications including coronary artery perforation, 
coronary artery dissection, aortic dissection, cardiac free wall perforation, or systemic 
embolization of a native or bioprosthetic leaflet 

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Rationale for primary safety endpoint 
The primary safety endpoint tests whether a subject tolerates attempted BASILICA using the 
TELLTALE guidewire. The endpoint is assessed at discharge to allow subjects to recover from 
general anesthesia, when required, to assess for stroke. Recovery of debris inside cerebral 
embolic protection devices, if employed, does not constitute systemic embolization, which is a 
common event after TAVR. 
 
4.6 
Secondary Endpoint: 30-day Safety 
The secondary endpoint is 30-day safety, as assessed by freedom from MACE (according to 
VARC-3 [30]) at 30 days, including freedom from all of the following: 
• All-cause mortality 
• All stroke (disabling and non-disabling) 
• Bleeding VARC-3 Type 2 or greater (requiring two or more units of transfused blood or 
hemoglobin drop >3g/dL) 
• Major vascular, access-related, or cardiac structural complication (according to VARC-3, 
which includes coronary obstruction) 
• Acute kidney injury stage 3 or 4 
• Moderate or severe aortic regurgitation 
• New permanent pacemaker due to procedure-related conduction abnormalities 
• Surgery or intervention related to the TELLTALE device 
Rationale for secondary endpoints 
The secondary endpoint is derived from a community safety standard that has recently been 
updated, VARC-3[30]. It is assessed at thirty-days according to VARC-3. 
4.7 
Exploratory Endpoints 
• Primary and secondary endpoints among subjects with native versus bioprosthetic disease 
• Stroke: disabling and non-disabling 
• Coronary stenting: snorkel (heterotopic) and orthotopic (through TAVR stent cells), to 
prevent or treat leaflet-induced coronary obstruction before (preemptive) and after (bailout 
or cautionary) TAVR. 
• Facilitated BASILICA procedure success, as defined in section 0. 
• Composite safety (secondary endpoint) assessed at 90 days 
• Ability selectively to engage threatened coronary ostia after BASILICA-TAVR 
• Acute hemodynamic deterioration in the interval between BASILICA and TAVR 
• Outcomes of subjects who participate in live case demonstrations compared with those 
who do not  
Rationale for Exploratory Endpoints 
Coronary stenting related to leaflet obstruction is undesirable and may reflect failed or aborted 
BASILICA, typically in the heterotopic (“snorkel”) position. Orthotopic coronary stenting is 

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typically required to treat leaflet prolapse related to mechanical avulsion manifest typically as 
severe acute aortic regurgitation with hemodynamic compromise.  
TAVR can render coronary arteries inaccessible for later emergency PCI. We will capture the 
ability to selectively engage coronary arteries after BASILICA-TAVR. 
5 
STUDY DESIGN 
5.1 
Constant values 
Number of subjects 
90 
Number of subjects with native aortic valve failure, 
initially 
15 
Number of additional subjects with native aortic 
valve failure invited to participate as part of study 
expansion 
15 
Maximum number of subjects with native aortic 
valve failure 
30 
Number of candidates screened, up to 
180 
Number of enrollment sites 
15 
Follow-up duration per subject 
90 days 
Expected study duration 
12 months for enrollment + follow-up 
5.2 
Overall Design 
This is a prospective, open-label, single-arm, multi-center, independently-adjudicated 
investigation of BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to 
prevent Coronary Artery obstruction) using the Transmural TELLTALE guidewire system 
immediately before TAVR (transcatheter aortic valve replacement) in subjects at high risk of 
coronary artery obstruction, as defined in the selection criteria. 
NHLBI Division of Intramural Research is the data coordinating center. Subjects undergo the 
study intervention only at enrolling centers. 
5.3 
Scientific Justification for Initiating this Study  
The purpose of the study is prospectively to evaluate the safety and efficacy of 
BASILICA-TAVR performed with the TELLTALE guidewire system. 
Because coronary artery obstruction is a predictable and life-threatening complication, because 
pre-emptive “snorkel” stenting is considered an inappropriate and undesirable strategy, 
because subjects are not good candidates for alternative surgical aortic valve replacement 
treatment, and because the study devices are considered intrinsically superior to bedside-
modified commercial devices used for standard BASILICA, there is no control arm in this 
investigation. 
The study is intended to support commercialization of the TELLTALE Guidewire System. We 
believe the study objectives cannot be met in vitro, using cadaver or surgical specimens ex vivo, 
nor using naïve or diseased animal models in vivo. Moreover, this study offers the prospect of 
direct benefit to subjects. Therefore clinical evaluation is reasonable.  

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5.4 
Scientific Justification for Duration of Study Follow-up 
The complications of BASILICA are evident upon procedure conclusion. Out of caution, adverse 
events are assessed upon hospital discharge and again after 30 days. 
In the prospective BASILICA IDE trial, using “off-label” bedside modification of commercially 
available catheter tools, there were no new adverse events that could be attributed specifically 
to BASILICA after 30 days. Specifically, there were no new thrombotic events (no stroke, no MI, 
no coronary obstruction, no transcatheter aortic valve failure, no increase in valve gradients), 
the coronaries remained clinically patent, no heart failure admissions, and no BASILICA related 
deaths.  
Moreover, we do not believe there is a plausible scientific rationale to suspect adverse events 
after discharge. In native and valve-in-valve TAVR, the prior valve tissue is disrupted and 
distorted by TAVR implantation. BASILICA does not significantly alter this disruption. 
It is not clear whether BASILICA increases the risk of stroke compared historically against TAVR 
without BASILICA. Neurological events were identified in our early prospective BASILICA IDE 
trial (n=30) [3, 24] but not evident in the non-adjudicated BASILICA registry (n=213) [4]. We do 
not believe BASILICA-related strokes occur after hospital discharge. Moreover, the “Protected 
TAVR” trial [NCT04149535] of TAVR stroke prevention using the Sentinel Cerebral Protection 
System (Boston Scientific), has a primary endpoint of “All stroke (hemorrhagic, ischemic, or 
undetermined status; disabling or nondisabling) through 72 hours post TAVR procedure or 
discharge.”  
Based on feedback from FDA CDRH, we plan a final follow-up encounter, remote or in-person, 
at 90 days. 
5.5 
Justification for single-arm study design 
We do not believe there is an appropriate comparator group for BASILICA TAVR using the 
TELLTALE guidewire.  
First, redo surgical aortic valve replacement appears to have higher risk of death, major 
bleeding, or prolonged hospital stay than valve-in-valve TAVR in general, among both 
intermediate and higher risk patients (Summarized in a recent meta-analysis [31]). Therefore 
surgical therapy is not an appropriate comparator, especially among high- or prohibitive-risk 
subjects. 
Second, we do not believe “snorkel stenting” is appropriate therapy or prophylaxis for patients 
at risk for acute TAVR-associated coronary obstruction. Snorkel stenting is “off-label,” the 
devices lack sufficient radial strength to separate the TAVR from the wall of the aortic root or 
sinotubular junction, coronary stents in this heterotopic position risk deformation and 
thrombosis, expose the patient to prolonged or indefinite antiplatelet and antithrombotic 
pharmacotherapy with attendant bleeding risk, and interfere with safe future re-access to the 
coronary arteries for PCI. We do not endorse snorkel stenting for any patient when BASILICA or 
surgery is an option. 

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Third, we believe many candidates are offered no definitive therapy for aortic valve stenosis or 
bioprosthetic valve failure when they are at high risk of coronary obstruction. We attribute this 
un-documented phenomenon to operator inexperience and the recent guidance provided to 
transcatheter heart valve manufacturers that BASILICA proctorship may be construed as 
inappropriate marketing. Part of our motivation to develop the TELLTALE guidewire system is to 
empower industry-supported proctors and operators to offer BASILICA when needed by their 
patients. 
Absent standard of care for patients at risk of TAVR-induced coronary obstruction and at high 
or prohibitive risk of surgical aortic valve replacement, we are unable to identify a suitable 
comparator group. Among our clinical investigation group, several physicians believe 
randomization to surgery or snorkel-stenting to be unethical.  
6 
STUDY POPULATION 
6.1 
Inclusion Criteria 
In order to be eligible to participate in the study, candidates must meet all of the following 
criteria: 
• Adults age ≥ 21 years 
• High or prohibitive risk of surgical aortic valve replacement according to the local 
multidisciplinary heart team 
• Undergoing TAVR for bioprosthetic aortic valve failure or native aortic stenosis (“on-label” 
TAVR) 
• Local multidisciplinary heart team determines subject to be at high risk of TAVR-induced 
coronary artery obstruction 
• Deemed likely to suffer coronary artery obstruction from TAVR based on NHLBI Core lab 
analysis of CT, any of 
o Risk is narrow Sinus of Valsalva: (a) Leaflet height is greater than coronary artery 
height, and (b) Virtual transcatheter valve-to-coronary (VTC) distance < 4mm 
o Risk is Sinus sequestration: (a) Threatening leaflet height is greater than sinotubular 
junction, and (b) Virtual transcatheter valve-to-sinotubular-junction distance (VTS) < 
2mm at the affected Sinus 
• Concurrence of the Study Eligibility Committee 
• Able to understand the protocol, consents in writing to participate, and willing to comply 
with all study procedures for the duration of the study 

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6.2 
Exclusion Criteria 
• Requires doppio (two-leaflet) BASILICA 
• Flail target leaflet at baseline 
• Excessive target aortic leaflet calcification (no basal calcium-free window or potentially 
obstructive calcific masses) on baseline CT 
• Planned provisional (pre-position coronary artery) stents despite BASILICA 
• Requires non-femoral access 
• Requires concomitant procedures during TAVR (such as percutaneous coronary intervention 
for baseline obstructive coronary artery disease) 
• Chronic kidney disease KDIGO stage 4 or 5 (eGFR < 29 ml/min/1.73m2) or renal replacement 
therapy 
• Not expected to survive for 12 months 
• Pregnant at the time of intended treatment (day 0) 
6.3 
Enrollment Quota 
A subset of subjects will have native aortic valve failure (initially n=15). Sequential enrollment 
will accommodate this quota. A "study expansion" IDE amendment increased this quota from 
15 to a maximum 30.   
6.4 
Rationale for selection criteria 
The selection criteria allow enrollment of the intended population with little anticipated 
selection bias. 
Children are excluded because children in general are not eligible for transcatheter aortic valve 
replacement. There is no maximum eligibility age because there is no scientific basis for age-
based exclusion per se. 
The CT criteria for anatomic eligibility based on valve-to-coronary distance and valve-to-sinus 
distance are based on prior reports [2] and experience [3].  
Excessive target leaflet calcification can exclude candidates from BASILICA based on two 
criteria: 
(1) Confluent leaflet calcification on CT at the intended basal traversal target reduces the 
likelihood of successful electrosurgical leaflet traversal. Conversely, any size calcium-
free window at the leaflet traversal target will allow successful electrosurgical traversal.  
(2) Calcific masses, defined as aortic native or bioprosthetic leaflet masses that, if displaced 
centrifugally by TAVR, are predicted by CT (“displacement/rotation along the hinge 
point”) to obstruct coronary artery ostia by “mass effect.” Such pathology is not 
amenable to BASILICA [5].  
Subjects are eligible if they are at high or prohibitive risk of surgical aortic valve replacement 
based on two randomized clinical trials, with two different transcatheter heart valves, that 
showed non-inferiority of TAVR versus surgical aortic valve replacement[32, 33]. 
Flail baseline leaflet is excluded because of risk of leaflet prolapse after successful traversal and 
laceration [35]. Excessive leaflet calcification is excluded because it prohibits traversal, or when 

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it risks coronary obstruction through a mechanism (such as mass) not amenable to prevention 
by BASILICA. 
Concomitant procedures might induce complications that confound assessment of TELLTALE-
related complications, and are therefore excluded. Non-femoral access is associated with a 
higher risk of complications and such candidates are therefore excluded. 
Pregnant candidates are excluded because they are generally excluded from elective 
transcatheter aortic valve replacement. Contraception is not required of subjects because 
research-related radiation is confined to the chest and only occurs on study day 0. 
Cognitively-impaired candidates are excluded based on our experience with inability to comply 
with quality-of-life questionnaire instruments, and frequent unwillingness to return for follow-
up after TAVR in protocols such as this one. 
The inclusive selection criteria and geographic extent of enrolling sites are expected to allow 
recruitment of a diverse economic, ethnic, and racial mix of patients that reflects the incident 
disease. 
Doppio BASILICA is excluded because discordant first and second leaflet results would impact 
assessment of the primary efficacy endpoint. [34][34][4][25] 
6.5 
Inclusion of Vulnerable Subjects 
Inclusion of Pregnant Women, fetuses or neonates 
Not applicable. 
6.6 
Lifestyle Considerations 
Not applicable 
6.7 
Screen Failures 
Study eligibility is based entirely on clinical records and medically indicated imaging studies. 
Subjects consent to participate in the study before undergoing any study-specific activity. 
Subjects are classified as screen failures if they undergo study-specific catheterization but NOT 
an attempt at BASILICA using the TELLTALE guidewire system. 
Baseline data acquired for screen failures are retained to facilitate reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. 
In case of attempted but unsuccessful TELLTALE BASILICA-TAVR leaflet traversal or laceration, 
subjects are followed for 30 days to assure freedom from screening- or procedure-related 
adverse events.  
Subjects are eligible for repeat screening and enrollment, in which case they are assigned new 
subject specific identifying numbers (SSPIN). 

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6.8 
Strategies for Recruitment and Retention 
Subjects will be recruited from the Structural Heart Disease clinical programs of the 
participating medical centers. 
We expect to accrue at least one subject per month per site from among enrollment centers. 
There is no subject enrollment at NIH Clinical Center. 
The distribution of planned enrolling sites assures accessibility of the trial to ethnically, racially, 
economically, and geographically diverse populations. The study will track sex, age, ethnicity, 
and racial background of subjects. 
Once recruited, subject retention rate is expected to be high because follow-up activities are 
not onerous and are timed to correspond with routine follow-up medical care. 
Costs 
Subjects are responsible for the costs of medical care associated with participating in this 
protocol. 
NHLBI is the Sponsor, which automatically qualifies sites for CMS reimbursement for costs of 
research-related medical care, according to the CMS Clinical Trial Program (CTP), for CMS 
beneficiaries. The CTP policy is described on 
https://www.cms.gov/Medicare/Coverage/ClinicalTrialPolicies/index.html. 
The result is that CMS is “explicitly authorize[d to provide] payment for routine patient care 
costs…and costs due to medical complications associated with participation in clinical trials.” 
The TELLTALE system test articles are provided without cost by the manufacturer, Transmural 
Systems. 
Compensation 
Candidates and subjects receive no compensation for screening or for participating in this 
study. 
7 
STUDY INTERVENTION 
7.1 
Test articles and Indications for Use 
Device Description 
Based on the clinical learnings from the NIH-sponsored BASILICA IDE with off-label/off-shelf 
devices, Transmural Systems collaborated with Dr. Lederman at the NIH and principal site 
investigators of the IDE (Drs.  Jaffar Khan, Toby Rogers, Adam Greenbaum and Vasilis 
Babaliaros) to design the TELLTALE Electrosurgical Guidewire System, providing more reliable 
devices for the procedure.   
The TELLTALE Electrosurgical Guidewire System is comprised of the TELLTALE Guidewire and 
accessories to aid with the preparation, placement and use of the guidewire.  The System 
includes: 

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• TELLTALE Guidewire 
• TELLTALE Accessories 
o Spring-loaded connector cable 
o Guide catheters (for left coronary cusp and for right coronary cusp)  
o Insulation Envelope 
o Insulation Tube 
o Denuder/Kinker  
o Guidewire grippers 
Indications for Use 
The TELLTALE Electrosurgical Guidewire System is indicated for transcatheter electrosurgical traversal 
and laceration of native and bioprosthetic tissue in patients at risk of coronary obstruction during TAVR. 
System Components 
TELLTALE Guidewire 
The TELLTALE Guidewire has an outer diameter of 0.014” and a working length of 310cm (Figure 
5).   It is composed of a 304V stainless steel guidewire covered with an outer insulative layer. The 
distal tip and proximal end of the guidewire are uninsulated.  The TELLTALE Guidewire mid-shaft 
is provided to the user fully insulated to protect the operator from RF energy when the 
uninsulated guidewire tip is used for electrosurgical leaflet traversal inside the patient (Figure 5). 
The proximal end of the TELLTALE Guidewire, which has no patient contact, is uninsulated and 
gold-plated to allow for connection to an electrosurgery generator to facilitate the delivery of 
monopolar RF energy to the cutting surfaces of the device.  
There are two cutting surfaces of the TELLTALE Guidewire. 
1) the distal tip for leaflet traversal 
2) a mid-shaft cutting location for leaflet laceration (approximately 160cm from the distal 
tip).  
The mid-shaft of the TELLTALE guidewire is identified by a 10mm gold marker band which is 
radiopaque.  The mid-shaft cutting surface is created by the user by removing the insulative 
coating (denuded) after the distal tip is used to traverse through tissue.  Therefore, the mid-shaft 
cutting surface does not contact the patient during electrosurgery using the distal tip. When used 
for the BASILICA procedure, the distal tip does not contact the patient during electrosurgery 
when RF energy is turned on for use at the mid-shaft cutting location.   
The TELLTALE Guidewire design and procedure outlined in the Instructions for Use (IFU) will 
ensure that the non-insulated portions of the wire are only in contact with the patient in an 
intentional way during the procedure.   

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Figure 5.  Image of TELLTALE Guidewire with cross section of the denuded area (prior to kinking).   The insulative outer layer of 
the guidewire is clear but is represented in figure 4 with the gray color. 
TELLTALE System Accessories: 
• 
Spring Loaded Connector (Figure 6): A detachable spring-loaded connector cable that plugs into the 
RF generator and allows for a secure insulative connection between the TELLTALE Guidewire and the 
generator. The detachable connector allows for exchange of catheters over the TELLTALE Guidewire 
as needed during the procedure.  
• 
Transmural Pachyderm Guide catheters (Figure 7): The guide catheters are specifically shaped to aid 
in leaflet traversal by allowing physicians to select the traversal location and providing backup support 
for TELLTALE Guidewire leaflet traversal.  
• 
Insulation Envelope (Figure 8): The insulation envelope is only used during the traversal procedure. It 
is provided as an added layer of insulation to protect the user and patient from un-intended RF energy. 
• 
Insulation Tube:   The insulation tube is a plastic tube provided for use during laceration of the 
leaflet only.  It is provided as an insulated cover for the denuded distal tip of the guidewire to 
protect the user and patient from un-intended RF energy.     
 
 
 
Figure 6. Image of Spring-loaded connector 
cable for connection to RF Generator 
Figure 7. Image of Transmural 
Pachyderm Guide Catheters for the 
left and right coronary cusps, 
respectively 
Figure 8. Image of Insulation 
Envelope 
• 
Denuder/Kinker (Figure 9):  The Denuder/kinker is provided to (1) create a reproducible denuded, or 
uninsulated, area at the mid-shaft location of the TELLTALE Guidewire for laceration and (2) kink the 
TELLTALE Guidewire at the lacerating surface to produce the required angle for the BASILICA 
procedure.  

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Figure 9. Image of Denuder and kinker.  (Left) Open position,  (Middle) Closed position, (Right) Denuded and Kinked guidewire 
• 
Guidewire gripper (Figure 10):  The guidewire gripper is attached to a standard Y-adaptor and clamps 
onto the TELLTALE Guidewire to assist with guidewire traction during the procedure. 
 
Figure 10. Image of Guidewire Grippers (Left) Open position, (Right) Closed position 
The generator connector cable, gripper insulation envelope, insulation tube, and denuder/kinker 
are non-patient contact parts and are constructed of standard medical materials.  
7.2 
BASILICA-TAVR using the TELLTALE System 
Study Intervention Description 
Candidates will be identified by the participating structural heart disease programs. In 
evaluation of aortic valve disease, candidates will undergo clinical evaluation, 
echocardiography, optional coronary arteriography, and contrast-enhanced gated cardiac CT. 
Eligibility will be reviewed and proposed by the local multidisciplinary heart teams. Candidates 
will then undergo central eligibility review by the sponsor and designated investigators. If 
deemed eligible, candidates will be offered participation in the study. 
Once enrolled, subjects will undergo baseline assessment and blood tests. 
Subjects will be admitted to the hospital and undergo TAVR with BASILICA using the Transmural 
TELLTALE guidewire system. They will undergo primary endpoint assessment before discharge. 
The TELLTALE BASILICA-TAVR procedure is planned from a contrast-enhanced CT of the heart to 
select a suitable transcatheter heart valve size, predict suitability of the sub- and supra-annular 

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landing zone, and predict post-TAVR coronary obstruction related leaflet encroachment on the 
sinotubular junction and coronary artery ostia. Knowledge of the aortic valve operative history 
is integrated into this assessment. These data are used to select a BASILICA traversal point, 
radiographic landmarks, and fluoroscopic projection angles. 
The procedure is performed under general anesthesia or under moderate sedation at the 
discretion of the institutional heart team. The TELLTALE BASILICA procedure has five steps: (1) 
engagement of the target leaflet with a guiding catheter and optional commercial deflectable 
guiding sheath; (2) electrosurgical leaflet traversal with the TELLTALE guidewire, (3) preparation 
and positioning of the TELLTALE guidewire electrosurgical leaflet laceration surface; (4) 
electrosurgical leaflet laceration with the TELLTALE guidewire, immediately followed by (5) 
TAVR. These are all guided by fluoroscopy, with adjunctive echocardiography as needed. 
 
Research study participation is defined as beginning the moment BASILICA traversal is 
attempted. This is in case TAVR is found not to be indicated at the time of the index invasive 
procedure, or in case BASILICA guidewire traversal is not otherwise attempted. 
First catheter access is obtained typically via two arterial introducer sheaths (one for 
hemodynamics and angiography, one for TAVR, both also used for BASILICA) and at least one 
venous introducer sheath for temporary transvenous pacing. Large hydraulic-hub introducer 
sheaths may allow multiple guiding catheters to be introduced via a smaller number of arterial 
access sites. Anticoagulation with heparin or equivalent achieves an activated clotting time > 
300s. 
Hemodynamic and echocardiography measurements are recorded at baseline including 
gradients across the aortic valve, severity of valvular obstruction and severity of valvular 
regurgitation. 
Two retrograde catheters are positioned, using a guidewire anchor as needed, in the LVOT and 
aorta respectively. Care is taken to avoid entrapment of mitral valvular structures. A snare 
catheter is positioned in the LVOT. A TELLTALE system guiding catheter, with- or without- a 
tandem coaxial catheter or microcatheter, directs the TELLTALE electrosurgery guidewire, 
against the base of the coronary cusp targeted for laceration, using fluoroscopic and/or 
echocardiographic guidance. Alternative guiding catheters are employed as described in the 
TELLTALE Instructions for Use.  
Leaflet traversal is accomplished by transcatheter electrosurgery by connecting the 
TELLTALE.014” guidewire to an electrosurgery generator during a short burst of “pure, cutting” 
radiofrequency energy at approximately 10-30W as required. The guidewire is repositioned as 
needed until it crosses the aortic leaflet and is snare-retrieved and externalized. Nonionic flush 
(dextrose 5%) can be administered as needed via the guiding catheters to reduce guidewire 
char and thromboembolism. 
Operators are encouraged to perform contrast angiography through the traversal guiding 
catheter to demonstrate position of TELLTALE guidewire traversal. 

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Next the TELLTALE guidewire is appropriately kinked and denuded to prepare the leaflet 
laceration surface, which is positioned across the intended valve leaflet. 
A left ventricular pigtail catheter, with or without guidewire, may be positioned before or after 
the laceration step, at operator discretion. 
Transcatheter cerebral embolic protection devices are employed at operator discretion. 
Next TELLTALE BASILICA is accomplished by electrosurgical laceration during nonionic flush and 
traction on the TELLTALE guidewire. Electrosurgery is applied in short bursts until laceration is 
successful and complete, as evidenced by free withdrawal of the guidewire. 
Hemodynamics are recorded quickly after laceration before TAVR. Predilatation, including 
intentional disruption of the bioprosthetic valve frame, is performed at operator discretion, 
before or after TAVR. Then TAVR is performed using established techniques typically during 
rapid ventricular pacing. The device size and inflation volumes are selected and applied at the 
discretion of the operator. Post-dilatation is performed at operator discretion to achieve an 
optimum TAVR result. 
Coronary artery patency, and access through TAVR device struts, is established using selective 
coronary angiography. 
Completion hemodynamics and echocardiography are recorded. Finally, percutaneous arterial 
and venous vascular hemostasis is obtained and the subject convalesces in the appropriate 
inpatient recovery unit. 
Before discharge, follow-up transthoracic echocardiography is recorded. Clinically-indicated 
blood test results are recorded for research. These are repeated at 30 days. 
Anticoagulation and antiplatelet therapy is prescribed after discharge at the physicians’ 
discretion, and is recorded. 
All subjects are to be enrolled in the TVT-Registry post-marketing TAVR registry. 
Subjects would receive continuing care from their primary physicians and/or cardiologists with 
consultant input as requested from the structural heart disease program. 
Subjects may undergo a post-TAVR medically-indicated contrast-enhanced CT at their 
physicians’ discretion, in which case NHLBI requests to receive and analyze the images. 
Subjects’ participation in the study concludes at the 90 days follow-up and termination visit. 
Study duration 
Subjects participate through the 90 days follow-up and termination visit. 
We aim to complete the study in 12 months for enrollment + follow-up. 
Number of enrollment sites 
Up to 15 sites will enroll and treat subjects in this study. 

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7.3 
Preparation/Handling/Storage/Accountability 
Acquisition and Accountability 
The investigational TELLTALE systems will be shipped to sites and stored in a secured location 
with a written receipt and accountability log. Alternatively the systems may be transported and 
handled by manufacturer representatives, and comparably recorded in the accountability log. 
Formulation, Appearance, Packaging, and Labeling 
This is described in the manufacturer instructions for use. 
Product Storage and Stability 
This is described in the manufacturer instructions for use. 
Preparation 
The TELLTALE system is prepared according to the accompanying manufacturer instructions for 
use. 
7.4 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable for an open-label study. 
7.5 
Study Intervention Compliance 
Protocol compliance will be assured by source document (medical record) to case-report-form 
data verification by independent data monitors. 
7.6 
Concomitant Therapy 
There are no restrictions on concomitant therapy. 
 
8 
DISCONTINUING OR WITHDRAWING STUDY INTERVENTION OR SUBJECT  
8.1 
Discontinuation of Study Intervention 
The TELLTALE guidewire system is a single-use device with no components implanted. It is used 
during a single BASILICA-TAVR procedure involving a permanent implant that is not intended to 
be removed. 
8.2 
Aborted or abandoned TELLTALE BASILICA-TAVR 
In the case of aborted TELLTALE BASILICA-TAVR without successful leaflet laceration, subjects 
may go off-study as soon as they are clinically stable, but at least 30 day follow-up. Such 
subjects need not undergo additional follow-up for exploratory efficacy or natural history 
assessment. 

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8.3 
Subject Discontinuation/Withdrawal from the Study 
Reasonable efforts will be made to undertake protocol-specified safety follow-up procedures to 
capture adverse events and adverse device effects, both serious and not, as well as 
unanticipated problems, through the 30-day follow-up visit. 
Subjects are free to withdraw from participation in the study at any time upon request. If a 
subject repeatedly and consistently declines to return for follow-up evaluation, the 
investigators may be forced to withdraw the subject from the study prematurely. 
However, since the study intervention (TELLTALE BASILICA-TAVR procedure) will already have 
been performed, withdrawal means these subjects would be withdrawing from follow-up of 
endpoints and adverse events. For the sake of safety, subjects will be advised not to withdraw. 
Pregnancy after TELLTALE BASILICA-TAVR will not lead to study discontinuation because there is 
no research-related radiation or other research procedures that threaten the fetus or the 
pregnancy. 
8.4 
Loss to Follow-up 
A subject will be considered lost to follow-up if he or she fails to return for 2 consecutive 
scheduled visits and despite attempts at contact by the study site staff. 
The following actions must be taken if a subject fails to return to the enrollment center for a 
required study visit: 
o The site will attempt to contact the subject and reschedule the missed visit and counsel 
the subject on the importance of maintaining the assigned visit schedule and ascertain if 
the subject wishes to and/or should continue in the study. 
o Before a subject is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the subject (where possible, 3 telephone calls to the 
subject, contact to the referring physician, and, if necessary, a certified letter to the 
subject’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the study file. 
o Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of "lost to follow-up." 
9 
STUDY ASSESSMENTS AND PROCEDURES 
9.1 
Screening Procedures 
Screening prior to consent is based entirely on clinically-indicated medical encounters, blood 
tests, laboratory and clinical examinations (cardiac catheterization, echocardiography, CT, MRI, 
blood tests), review of medical records, and communication with candidates (in-person, via 
telephone, via telepresence, in writing, or via email).  

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The screening data are reviewed by the local multidisciplinary heart team, and then are 
reviewed by the Central Clinical Eligibility Committee before screening is complete. Candidates 
are only invited to participate if eligible. 
Some sites will use a screening consent to abide local institutional requirements before 
transmitting medical records to screen for eligibility. 
Screening centers will comply with Health Insurance Portability and Accountability Act (HIPAA) 
if applicable. 
9.2 
Efficacy Assessments 
Efficacy assessments are performed by qualified laboratories and staff at enrolling centers. 
Standard clinical examinations (such as vital signs and symptom classification), clinical blood 
testing, and clinical cardiac imaging procedures (such as echocardiography, cardiac CT, cardiac 
MRI) are performed by clinical laboratories at the enrolling centers.  
CT assessments (on baseline exam, not efficacy): valve-to-coronary (VTC) and valve-to-sinus 
(VTS) distance. These are analyzed by a NHLBI core laboratory. 
Fluoroscopy assessments (post-TAVR coronary arteriography) includes coronary patency and 
ability to engage the coronary artery ostium with a catheter. These are analyzed by a NHLBI 
core laboratory. 
Echocardiography assessments include transvalvular gradient, paravalvular leak, mitral valve 
injury . These echocardiographic assessments are standard and do not require core lab analysis. 
These are not analyzed by a NHLBI core laboratory. Instead, parameters are extracted for 
official reports from local echocardiography laboratories. As a result, certain fields may be 
missing for individual or focused examinations, such as volumes, continuity-equation valve 
areas, etc. These will be recorded as missing and not as protocol deviations.  
Standard research assessments (questionnaires such as KCCQ-23) are performed by qualified 
staff at enrollment centers according to a study Manual of Operations and according to an 
instruction-oriented Case Report Form. 
9.3 
Safety and Other Assessments 
Standard safety assessments (adverse event assessments) are performed by qualified staff at 
enrollment centers according to the Protocol Schedule of Activities and a study Manual of 
Operations and according to an instruction-oriented Case Report Form. 
Safety assessments follow a structured adverse event case report form and are corroborated by 
independent data monitors and, for primary endpoints, by an independent clinical events 
adjudication committee. 
Assessment of neurovascular events (stroke and TIA) 
For candidates without prior stroke or transient ischemic attack (TIA), formally-trained and 
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NIH Stroke Score. If there is no clinically evident TIA or stroke, the predischarge assessments of 
modified Rankin Score and NIH Stroke Score will be performed by certified research 
coordinators. Otherwise they will be performed by consulting neurology specialists. 
For candidates with prior stroke or TIA , consulting neurology specialists will perform baseline 
and pre-discharge assessments including modified Rankin Score and NIH Stroke Score. 
Training and certification will be obtained from a service such as BlueCloud. 
9.4 
Adverse Events and Serious Adverse Events 
In this protocol, TAVR is clinically indicated. BASILICA using the TELLTALE Guidewire System is 
performed for the purpose of research. 
Definition of Adverse Event 
Adverse events: Any untoward medical occurrence in a human subject, including any abnormal 
sign (e.g., abnormal physical exam or laboratory finding), symptom, or disease, temporally 
associated with the subject’s participation in the research, whether or not considered related to 
the subject’s participation in the research (21 CFR 312.32 (a)). 
This includes: 
• 
Expected events related to the subject’s disease process during active enrollment in the 
research protocol and do not directly result from use of the investigational device or 
study. 
• 
Procedural events directly related to the BASILICA-TAVR cardiac catheterization 
procedure and recovery from the procedure and do not directly result from use of the 
investigational device. 
Definition of Serious Adverse Events (SAE) 
Serious Adverse Event (SAE): A serious adverse event that results in any of the following and 
NOT directly related to the device (21 CFR 812.3(s)). This includes any event that 
• 
Results in death 
• 
Is life-threatening (places the subject at immediate risk of death from the event as it 
occurs); 
• 
results in in-patient hospitalization or prolongation of existing hospitalization; 
• 
results in a persistent or significant incapacity; 
• 
results in a congenital anomaly/birth defect (not relevant to this study); or 
• 
based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
this definition. 
Definition of Adverse Device Effect (ADE) 
Adverse Device Effect (ADE): Any untoward or unintended response to a medical device. This 
definition includes any event resulting from insufficiencies or inadequacies in the instructions 
for use or the deployment of the device or any event that is a result of user error. 

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This includes procedural events directly related to the TELLTALE BASILICA procedure and 
recovery from the procedure in addition to use of the investigational TELLTALE devices. 
Definition of Serious Adverse Device Effect (SADE), Anticipated Adverse Device Effect (AADE) 
and Unanticipated Adverse Device Effect (UADE)  
Serious Adverse Device Effect (SADE): An adverse effect that may have been or is attributed to 
the use of the device and produce an injury or illness that is life-threatening, results in 
permanent impairment or damage to the body, or requires medical or surgical intervention to 
prevent permanent harm to the body. 
Anticipated Adverse Device Effects (AADEs): An AADE is an adverse event with a reasonable 
possibility that the device or procedure caused or contributed to the event. Please refer to the 
list of anticipated adverse device effects (AADE) in section 0 on page 21. 
Unanticipated adverse device effect (UADE): 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. 
Classification Adverse Events 
Severity of Event 
Category 
Description 
Mild 
Awareness of symptom. Not expected to have a clinically significant effect 
on the subject’s condition. Not surpassing the expected standard medical 
intervention. 
Moderate 
Condition creates a level of discomfort that interferes with the subject’s 
usual activity or affects clinical status. May require medical intervention.  
Severe 
Incapacitating and significantly affects the subject’s clinical status. Likely 
requires medical intervention and prolonged hospitalization.  
 

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Relationship (Attribution) to Study Intervention 
Classification Description 
Definite 
The event is clearly related to the research protocol. 
Probable 
The event is likely related to the research protocol. The event has a 
reasonable temporal relationship to the research device or research 
procedure and alternative causes, such as underlying disease, concomitant 
medications, or concomitant treatment-can be excluded. 
Possible 
The event may be related to the research protocol. The event has a 
reasonable temporal relationship to the research device or research 
procedure, and attribution of the event to the device or procedure cannot 
be excluded. However, alternative causes—such as underlying disease, 
concomitant medications, or concomitant treatments—are presumably 
responsible. 
Unlikely 
It is doubtful the event is related to the research protocol. The event can 
reasonably be explained by other factures, including underlying disease, 
concomitant medications, or concomitant treatments.  
Unrelated 
The event is clearly not related to the research protocol. There either is no 
temporal association with the research device or procedure, or the event is 
readily explained by other factures, including underlying disease, 
concomitant medications, or concomitant treatments.  
Expectedness 
Please see the list of anticipated adverse device effects (AADE) in section 0 on page 21. 
The NHLBI Principal Investigator and the Participating Site Principal Investigator will be 
responsible for determining whether an adverse event (AE) is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the study intervention. 
Intervals and Frequency for Event Assessment and Follow-Up 
Adverse event assessment, recording, and reporting will start on Day (0), upon attempt at a 
TELLTALE BASILICA-TAVR procedure and will continue through the 90 days follow up. 
New events or conditions present at baseline that increase in severity will be recorded and 
evaluated and reported on the adverse event case report form.  
All adverse events (AE) and adverse device effects (ADE) will be recorded and reported to the 
Sponsor using study specific case report forms, and then entry into the NIH electronic data 
base, CTDB (or equivalent), through the 30 days follow-up.  All  serious adverse device effects 
(SADE), serious adverse events (SAE), unanticipated device effects (UADE), and unanticipated 
problems (UP) will be recorded through the 90 days follow up. Adverse event case report 
forms and all source documentation supporting the adverse event will be transmitted to the 
Sponsor for review prior to entering the event into CTDB.  

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Adverse Event Reporting 
Unanticipated adverse device effects (UADE) and Unanticipated problems (UP) must be 
submitted to the Sponsor for review and approval prior to submitting to the Reviewing IRB 
(Advarra). Sponsor will review, and if appropriate, provide suggestions to the site Principal 
Investigator. The enrolling site will then enter event into CTDB, and submit the report to 
Advarra in accordance with Advarra’s policies. Sponsor will then submit final report to the 
NHLBI Office of the Clinical Director (OCD). 
It is the responsibility of the site investigator to report adverse events and adverse device 
effects to their respective HRPP/IRB offices or other regulatory bodies according to their local 
institutional reporting requirements. 
Reporting obligations and deadlines are summarized in Appendix B. 
Site reporting to local institutional bodies  
In addition to reporting to Advarra and the Sponsor, the Site Principal Investigator is 
responsible for further reporting of events to their own institution per local reporting 
requirements. 
The NIH PI will report events to the NIH Office of Human Subjects Research Protections (OHSRP) 
in accordance with NIH HRPP Policy 801: Reporting Research Events found here: 
https://policymanual.nih.gov/3014-801 
Device Safety Reporting 
The Sponsor is responsible for device safety reporting to FDA. 
Investigators are required to submit a report of a UADE to the Sponsor. The Sponsor must 
immediately conduct an evaluation of a UADE and must report the results of the evaluation 
to FDA, Advarra, and participating investigators within 10 working days after the Sponsor first 
receives notice of the effect. Events of Special Interest 
Not applicable 
Reporting of Pregnancy 
Not applicable 
9.5 
Unanticipated Problems 
Definition of Unanticipated Problems (UP) 
Any incident, experience, or outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
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• Related or possibly related to participation in the research (“possibly related” means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• Suggests that the research places participants or others (which many include research 
staff, family members or other individuals not directly participating in the research) at a 
greater risk of harm (including physical, psychological, economic, or social harm) than 
was previously known or expected. 
 Unanticipated Problem Reporting 
The investigator will report unanticipated problems (UPs) to the Sponsor and Advarra. 
Reporting obligations and deadlines are summarized in Appendix B. 
9.6 
Protocol Deviations and Non-Compliance 
It is the responsibility of the investigator to use continuous vigilance to identify deviations 
and/or non-compliance.  The investigator is responsible for knowing and adhering to Advarra 
requirements. 
Reporting obligations and deadlines are summarized in Appendix B. 
Definition of Protocol Deviation and Non-compliance 
A protocol deviation is any changed, divergence, or departure from the IRB-approved research 
protocol. 
• Major deviations: Deviations from the IRB approved protocol that have, or may have the 
potential to, negatively impact the rights, welfare or safety of the subject, or to 
substantially negatively impact the scientific integrity or validity of the study. 
• Minor deviations: Deviations that do not have the potential to negatively impact the 
rights, safety or welfare of subjects or others, or the scientific integrity or validity of the 
study. 
Non-Compliance is a failure of an investigator to follow the applicable laws, regulations, or 
institutional policies governing the protection of human subjects in research, or the 
requirements or determinations of the Institutional Review Board (IRB), whether the failure is 
intentional or not. 
10 STATISTICAL CONSIDERATIONS 
10.1 Statistical Hypothesis 
The objective of this protocol is to test the safety and effectiveness of the TELLTALE guidewire 
system in accomplishing BASILICA leaflet traversal and laceration to prevent coronary artery 
obstruction in the study population. The primary efficacy endpoint and the primary safety 
endpoint are defined in sections 4.4 and 4.5. We will use the data from this study to estimate 
the event rates for the primary efficacy and safety endpoints. Due to limited sample size, the 
study is not powered to evaluate any statistical hypotheses based on these endpoints. 
10.2 Sample Size Determination 
The sample size is not statistically derived. 

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Up to 180 candidates will be consented until 90 subjects undergo attempted TELLTALE 
BASILICA-TAVR in this protocol.  
There is a revised quota of 30 subjects who must have native TELLTALE BASILICA-TAVR of the 90 
total enrolled subjects. This is based on initial quota of 15 subjects and subsequent study 
expansion by 15 additional subjects with native aortic valve failure. All subjects, including the 
expanded native cohort, will undergo analysis for primary, secondary, and exploratory 
endpoints. 
Rationale for Sample Size 
TAVR-induced coronary obstruction is rare but devastating [1, 2]. Therefore the potential 
patient population is small. 
The key clinically meaningful outcome is successful TAVR without coronary obstruction. We 
believe we are able to accomplish this using bedside-modified guidewires for BASILICA-TAVR. 
It is not clear whether BASILICA increases the risk of stroke compared historically against TAVR 
without BASILICA. Neurological events were identified in our early prospective BASILICA IDE 
trial (n=30) [3, 24] but not evident in the non-adjudicated BASILICA registry (n=213) [4]. 
FDA CDRH reviewers transmitted the following recommendation: 
We recommend increasing the size of the bioprosthetic valve subgroup to 60 subjects. 
This is based on a literature review of mortality and stroke rates in ViV TAVR studies that 
reported an average stroke rate (the lower of the two event rates) of approximately 
1.4%. We suggest that the sample size be large enough to have potential to detect 
whether the stroke rate with TELLTALE BASILICA increases 2-fold or greater compared to 
clinically reported rates. For an event with anticipated incidence rate of 2*1.4% = 2.8%, 
a sample size of 60 will provide > 80% probability that at least one stroke event will be 
observed. While we acknowledge that the study will not be hypothesis-based nor 
powered to detect differences in stroke/mortality, we believe these are important 
endpoints to consider when assessing safety and effectiveness of the BASILICA 
procedure with TELLTALE device, and will be incorporated into our final assessment of 
the totality of data. The suggested sample size of 60 provides reasonable confidence 
that the sample size is large enough to detect a rare event. 
The bioprosthetic and native valve subgroups do not necessarily need to be balanced in 
size. We continue to believe that if they are not balanced, that enrollment should be 
weighted in favor of the bioprosthetic group, since this group appears more likely to 
have adverse events. As noted above, we suggest that the bioprosthetic group sample 
size be increased to 60. You may consider maintaining an n=15 native valve sample size, 
for a total sample size of n=75. 
The investigators accept this recommended sample size. 
In amendment B, the sample size is increased from 15 to 30 among subjects with native aortic 
valve failure, for a total sample size of 90. 

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10.3 Cohorts for Analyses 
The analysis will be per-protocol, of subjects who undergo an attempt at TELLTALE BASILICA-
TAVR. 
Evaluable for toxicity 
Complications are reflected in the primary safety endpoint, in secondary endpoints, and 
exploratory endpoints described in section 4 beginning on page 24. 
Evaluable for objective response 
Efficacy is evaluated in the primary efficacy endpoint, in secondary endpoints, and exploratory 
endpoints described in section 4 beginning on page 24. 
10.4 Statistical Analyses 
Exploratory data analysis will assess for missing values and will generate data clarification 
requests as required. We expect few missing data. If there are missing data to evaluate the 
primary efficacy endpoint or primary safety endpoint for a study subject, the endpoint with 
missing information will be considered a failure for the applicable subject. The primary analysis 
will be based on the intention-to-treat (ITT) population that includes all study subjects.  We will 
also perform an as-treated analysis in a sensitivity analysis.  
For the primary efficacy endpoint, primary safety endpoint and secondary endpoint, we will 
estimate the event rate by the sample proportion of subject who meet the given endpoint with 
95% confidence interval. Descriptive statistics will be used to summarize the baseline 
demographic characteristics, subject and procedure characteristics, and the exploratory 
endpoints. For continuous variables, the mean (standard deviation) or median (interquartile 
range) will be presented. For categorical variables, the frequency and the percentage in each 
category will be presented. Exploratory post-hoc analyses will be performed as unusual 
observations and novel questions arise, including those requiring additional data abstraction 
from the source documents or images. 
In an exploratory analysis, results including the primary efficacy endpoint for device technical 
success and 30-day VARC3 safety will be compared with those outcomes from a previously 
completed study, the NHLBI BASILICA IDE protocol (NCT03381989) of bedside-modified 
traversal and laceration guidewires. Fisher’s exact tests will be used to compare these 
outcomes between two studies. 
The key study results (primary and secondary endpoints) will be analyzed by subgroups 
including indication (bioprosthetic versus native), site, census region, age (dichotomized by the 
sample median), non-white status, and sex. For each of the above baseline characteristics, the 
subgroup differences in the study outcome will be evaluated by the two-sided Fisher’s exact 
test at a significance level of 0.05. For the subgroup analysis of study sites,  the sites with 
smallest number of patients will be combined to have at least 5 subjects in the pseudo-site 
group. 
Statistical analysis will be performed or confirmed by the NHLBI study statistician. 

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10.5 Stopping Rule Guidance for Data and Safety Monitoring Board (DSMB) 
The mortality observed in the prospective NHLBI BASILICA IDE study (n=30) was 3.3%, and the 
12-month mortality was 10% [24]. The 30-day mortality observed in the retrospective 
multicenter international BASILICA registry (n=214) was 2.8%, and 12-month mortality was 21.5% 
[4]. 
In Amendment A, the stopping rules are adjusted to become more conservative, as stipulated by 
the DSMB before enrollment began. The study will be monitored to ensure that the mortality 
within 30-days after the procedure does not substantially exceed an anticipated rate. We 
anticipate the rate of 30-day mortality is 5% or less and determine the stopping rule by a Bayesian 
approach [36]. The stopping boundary is reached if the posterior probability that the 30-day 
mortality rate exceeds 5% is at least 90%.  We take our prior distribution to be a beta distribution 
so that our prior clinical opinion is worth 20% of the weight we will place on the new study data, 
which gives the prior parameters a =0.75, b =14.25. Hence when we make decisions about 
stopping the study, the data from the study will dominate over the prior opinion.  
The following table summarizes the threshold numbers for the stop rule boundary, which would 
lead to a recommendation to stop the study due to the excess 30-day mortality. The custom 
calculator is posted at https://rconnect.nhlbi.nih.gov/CTStopRule/. 
Number of subjects in the stratum 
Consider stopping if the number of deaths within 30 
days reaches 
2 - 5 
2 
6 - 18 
3 
19 - 31 
4 
32 - 46 
5 
47 - 61 
6 
62 - 75 
7 
We investigated the performance of the above stopping rule by a simulation study. In each 
simulation run, we generated a study with 75 independent Bernoulli trials, each with a true 
certain 30-day mortality, and compared these outcomes with the above stopping boundary to 
determine whether the study was stopped.  We repeated the simulation 100,000 times and 
computed the proportion of stopped studies using the above stopping rule.  The following table 
summarizes the performance of this stopping rule: 
True 30-day mortality rate 
0.025 
0.05 
0.075 
0.1 
0.15 
0.2 
Proportion of Stopped Studies 
0.022 
0.169 
0.454 
0.72 
0.963 
0.997 
Average number of subjects 
73.8 
67.6 
56 
43.3 
24.7 
15.6 
Average number of 30-day mortality 
1.9 
3.4 
4.2 
4.3 
3.7 
3.1 
These simulation results suggest that our stopping rule has a low probability stopping a study 
when the true 30-day mortality rate is 5% or less, and the probability of stopping a study is high 

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when the true 30-day mortality rate exceeds 5%.  There, we believe that our Bayesian stopping 
rule for 30-day mortality has satisfactory statistical properties. 
11 STUDY GOVERNANCE AND OTHER OPERATIONAL CONSIDERATIONS 
11.1 Sponsor Representative 
As the study Sponsor representative of this clinical study, Dr. Robert Lederman has the overall 
responsibility for the conduct of the study, including assurance that the study meets the 
regulatory requirements of the appropriate regulatory bodies. 
The Sponsor Representative is the point of contact for study sites to report all events of 
regulatory significance. 
General Sponsor Duties 
The Sponsor's general duties consist of submitting the appropriate regulatory applications, 
selecting investigators and sites, obtaining their signed agreement, providing them with the 
information necessary to conduct the study, assuring proper clinical protocol conduct, ensuring 
proper clinical site monitoring, ensuring proper monitoring of the investigation, ensuring study 
subject informed consent is obtained, and informing IRB and FDA promptly of any significant 
new information about the investigation. 
11.2 Site Selection and Training 
Site selection: 
Site selection will be based on 
• 
Physician expression of interest and availability of suitable study candidates at the site. 
• 
Site prior participation in IDE protocols evaluating a treatment of structural heart disease, 
with investigators willing and able to comply with the requirements of this protocol. 
• 
Preference is given to sites with high volume structural heart intervention programs, 
operators with high technical proficiency, and successful prior collaboration with NHLBI 
Division of Intramural Research. 
• 
Further preference is given to sites that have achieved high volume and proficiency with the 
BASILICA procedure. 
• 
Sites must demonstrate ability to obtain CT examinations that are technically satisfactory 
for consideration of BASILICA. 
Site training: 
The Sponsor Representative will ensure appropriate training in the technique of TELLTALE 
BASILICA-TAVR prior to enrollment at any participating institution. 
Site training will consist of 
• 
NHLBI Investigator and/or Sponsor didactic training about the technique, preclinical, and 
clinical experience to date. 
• 
Manufacturer training about operation of TELLTALE system study devices 

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• 
Proctored conduct of TELLTALE BASILICA procedures in patients at the study site, at the sole 
discretion of the Sponsor and/or NHLBI Principal Investigator.  
• 
Completion of training, and suitability for independent TELLTALE BASILICA-TAVR 
enrollment, will be certified by the NHLBI Principal Investigator and Sponsor Representative. 
• 
Other TELLTALE investigators and manufacturer representatives provide ongoing 
proctorship and observe procedures, in-person or remotely via video telepresence. 
11.3 Study Central Clinical Eligibility Committee 
Clinical data for all research candidates are confirmed by the study Central Clinical Eligibility 
Committee before enrollment. 
The Study Central Clinical Eligibility Committee consists of the NHLBI Principal Investigator and 
associate investigators, the site Principal Investigators, and a NHLBI core lab representative. A 
quorum of the committee requires a site Principal Investigator where the candidate is not to be 
enrolled, as well as at least two NHLBI investigators. In addition, at least one member at each 
Eligibility meeting must be free of actual or perceived financial conflict of interest. A 
manufacturer representative may participate in study eligibility meetings but not vote. The 
considerations and determination of the Study Central Clinical Eligibility Committee will be 
recorded. 
11.4 Core Laboratories 
The NHLBI CT and Fluoroscopy Core Laboratories will analyze baseline CT and procedure 
fluoroscopy.  
There is no echocardiography core laboratory for this study. 
11.5 Independent Data Monitor 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 
conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Conference on Harmonisation Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s). 
Monitoring for this study will be performed by the independent data monitor. 
Remote or on-site monitoring will be performed during the site initiation visit and periodically 
throughout study enrollment. There will be 100% source-data verification. 
The Sponsor and sites will be provided copies of monitoring reports within 30 days of visit. 
Details of clinical site monitoring are documented in a Clinical Monitoring Plan (CMP). The CMP 
describes in detail who will conduct the monitoring, at what frequency monitoring will be done, 
at what level of detail monitoring will be performed, and the distribution of monitoring reports. 
Independent audits will not be conducted by Study Sponsor. 

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11.6 Clinical Events Adjudication Committee (CEAC) 
An independent CEAC will review monitored data to assure accuracy. The CEAC will be an 
independent contractor, and the charter will be agreed between the NHLBI Principal 
Investigator and the CEAC after the contract is awarded, which will be after final IRB approval. 
The CEAC will review all of the following events that occur in 30 days follow-up interval 
- 
Deaths 
- 
Primary (Efficacy) and (Safety) Endpoints 
- 
Secondary (30-day safety) Endpoints 
The CEAC will classify relatedness of the above events to the TELLTALE system devices. CEAC 
adjudication prevails over Principal Investigator classifications. 
11.7 Data and Safety Monitoring Board (DSMB) 
The standing Data and Safety Monitoring Board (DSMB) appointed by the NHLBI Division of 
Intramural Research will monitor the safety of subjects in the study as described in the 
investigational plan. For oversight of this protocol, DSMB will employ full-time or ad hoc 
members with expertise in transcatheter structural heart disease intervention. Members of 
the DSMB are independent from the study conduct and free of conflict of interest. 
The NHLBI DSMB charter is on file with NHLBI and is approved by the NHLBI Director and/or 
NHLBI Clinical Director. 
The NHLBI DSMB will review the protocol progress report at six month intervals, or more 
frequently upon request of PI, IRB, and/or NHLBI Clinical Director. These progress reports are 
prepared by the NHLBI Principal Investigator and study staff. The DSMB may recommend early 
termination of the study for considerations of safety and efficacy. Unanticipated Adverse 
Device Effects (UADEs) will be reported to the DSMB following the same timelines as the IRB 
(See section 0 on page 46). 
In the case of death or serious UADE, if the Sponsor and the NIH Principal Investigator or DSMB 
determine that the event presents an unreasonable risk to the participating subjects, the 
clinical trial will be terminated within 5 working days after making that determination and not 
later than 15 working days after the Sponsor first receives notice of the effect. [21 CFR 812.46]. 
All clinical sites will be notified of this action. 
A “stopping rule” is described in section  10.5 on page 50 as non-binding guidance for the 
Investigators and the Data and Safety Monitoring Board to assure subject safety. This is based 
on anticipated 30-day mortality. This is intended to assist and not automate decision-making. 
11.8 Publications Committee 
The study publications committee consists of the NIH Principal Investigator and the local site 
Principal Investigators. 
Investigators may not independently publish, present, or disclose study results, in whole or in 
part, without permission of the Publications Committee. 

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11.9 Publication and Data Sharing Policy 
Human Data Sharing Plan 
Results of the study will be presented at scientific meetings and/or published in a peer 
reviewed scientific or medical journal. The results of the study will be released within 12 
months of study completion. 
Investigators may not independently publish or disclose study results without permission of the 
Publications Committee (See section 11.8). 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access 
to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-
Funded Clinical Trial Information and the Clinical Trials Registration and Results Information 
Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results 
information from this trial will be submitted to ClinicalTrials.gov. 
Data from this study may be requested by other researchers indefinitely after the completion of 
the one year timepoint by contacting the NIH Principal Investigator. 
Data transfer to collaborators 
De-identified (personally identifiable information and linking codes removed) data and images 
may be posted at the NHLBI Cardiovascular Intervention Structural Heart Image Data 
Repository (https://ledermanlab.nhlbi.nih.gov/repository/index.htm or equivalent). They are 
provided for the purpose of medical education and research. Data are de-identified, so that 
patients can not readily be identified, and are therefore not considered human research 
subjects research data under US 45CFR§46.104(d)(2)(i). 
De-identified images will also be transferred to collaborating investigators at academic and 
industry sites. They are provided for the purpose of medical education and research. 
Coded but linked data are provided to collaborators who require additional information, and 
with IRB approval of this protocol. This approach is used for the sake of quality control and/or 
quality assurance of the test article. These collaborators are: 
Recipient 
Organization 
Location 
Linkable 
Nasser Rafiee 
Transmural Systems 
Andover, MA 
Linked 
Stephanie Sellers, PhD 
University of British Columbia 
Vancouver, BC, CANADA 
Linked 
 

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11.10 Intellectual Property 
The Sponsor has full rights over any invention, discovery, or innovation, patentable or not, that 
may occur when performing the study. 
11.11 Informed Consent Process 
Consent/Assent Procedures and Documentation 
Subjects who are UNABLE to provide consent may NOT be enrolled. The use of a legally 
authorized representative (surrogate), is not permitted. Telephone or electronic consent are 
allowed for the optional screening consent; in-person consent is required for participation in 
the TELLTALE BASILICA TAVR protocol. 
The method of obtaining and documenting the informed consent and the contents of the 
consent complies with ICH- GCP and all applicable regulatory requirement(s). Research 
informed consent will be obtained by the local site Principal Investigator and local site 
personnel who are listed on the Delegation of Authority Log. The most recent IRB-approved 
consent will be used.  
The candidate will be asked to consider participating (consent) during a clinical encounter to 
discuss transcatheter aortic valve replacement (TAVR). The research procedure is a procedure 
adjunct to TAVR. 
The investigational nature and objectives of the trial, the procedures and treatments involved, 
and the risks and discomforts and potential benefits will be carefully explained in person to the 
candidate. The consenting process will be a verbal review of the IRB-approved consent in a 
language understandable to the subject, free of any exculpatory language to avoid any 
possibility of coercion. Candidates will be given ample opportunity to read the study consent in 
private and to discuss with family, personal physicians, or others as desired; to ask questions;  
and given sufficient time to determine whether or not to participate in the research study.  
The research informed consent document will be signed and dated in the presence of the 
authorized study staff, who will also sign and date as appropriate. The subject will then receive 
a hard copy of the informed consent document. 
The research consenting process will be documented in the subjects medical record with the 
signed and dated IRB-approved research consent. Electronic tools may  be employed for the 
optional screening consent.  
Subjects participating at covered entities will provide written Privacy Rule Authorization (aka 
“HIPAA Authorization”) to use and disclose individually identifiable health information for this 
protocol. Subjects will be counseled about privacy and confidentiality protections and 
provisions as part of the informed consent process. 

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Informed consent for non-English speaking subjects 
Enrolling sites will follow Advarra processes for short form consent of non-English speaking 
research participants. Advarra provides pre-approved short form consent templates in multiple 
languages. All other institutionally/organizationally-approved short form consents and 
translations in use at a research location or institution do not need to be submitted for Advarra 
review. If using a local short form consent, however, the investigator/site will need to also 
provide the subjects with the Advarra Short Form IRB Oversight Addendum, to ensure 
notification to the subject of Advarra as the IRB of record.   
Consent of Subjects who lose decision-making ability during the study 
Adults with decisional impairment are not eligible to enroll in the study. 
In the event subjects lose the ability to consent after the index TELLTALE BASILICA-TAVR, they 
will remain in the study, because the risk of investigation is confined to the index procedure. All 
additional data collected are required for clinical care, and the only residual risk is to privacy 
and confidentiality. 
Decision-making is assessed during scheduled follow-up events. When subjects lose decision-
making ability, affirmation of consent is sought directly from the Legally Authorized 
Representative (LAR) at the enrolling site. Individual sites will follow applicable laws, regulation 
and institutional policy. 
If the study team is unable to identify a Legally Authorized Representative, the team will seek 
guidance from their local institution. 
Having failed to obtain affirmation of consent, the subject is withdrawn from the study.  
11.12 Unscheduled Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to affected regulatory 
bodies including enrolling site Principal Investigators, Advarra, Sponsor (NHLBI Office of Clinical 
Director), NIH Principal Investigator, Device Manufacturer, and FDA.  
If the study is prematurely terminated or suspended, the NIH Principal Investigator (PI) will 
promptly inform study participants, the IRB, and Sponsor and will provide the reason(s) for the 
termination or suspension.  
Study participants will be contacted, as applicable, and be informed of changes to study visit 
schedule. 
 Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 

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• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB and, as applicable, the Food and Drug Administration 
(FDA). 
11.13 Confidentiality and Privacy 
In order to maintain subject privacy, accountability records, study reports, and communications 
will identify the subject by initials and the assigned subject number. 
However, medical records will be transmitted and stored as source documents and will retain 
patient names and/or medical record numbers, to allow physician-investigators to 
recommend medical therapies as appropriate, to avoid risk of mis-identification. 
In addition, electronic (DICOM-format) medical images transmitted for the purpose of this 
study will retain patient identifiers. 
Representatives from Transmural Systems may be present during the TELLTALE BASILICA-TAVR 
procedure. This is disclosed in the informed consent. 
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB, 
and/or regulatory agencies may inspect all documents and records required to be maintained 
by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The enrolling site will permit access to such 
records. 
The study participant’s contact information will be securely stored at each enrolling site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for the time period dictated by Advarra, Institutional policies, or Sponsor 
requirements, whichever is the longest. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the NIH. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will 
be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites and by NHLBI research staff will be secured and 
password protected. At the end of the study, all study databases will be de-identified and 
archived at the NHLBI. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH). This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help 
achieve the research objectives and promote participation in studies by helping assure 
confidentiality and privacy to participants.  

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As identifiable private information will be collected and stored for/by the NIH, the prospective 
subject will receive a privacy notice and be informed of the NIH Certificate of Confidentiality 
policy in the consent form. 
 
11.14 Future use of Stored Specimens and Data 
Data may be stored indefinitely. Imaging data in PACS may be stored indefinitely. 
Subjects consent to future use of their clinical and imaging data indefinitely, even upon 
withdrawal of consent. Following analyses of data for primary research purposes as described 
in the protocol, images suitable for future research will be stored. Any future research use of 
identifiable data not defined in the research protocol will occur only after IRB review and 
approval. 
Autopsy specimens will be handled according to local institutional medical standards and will 
be disposed accordingly. We do not intend to store these specimens for future use. 
See also Section 11.13, Confidentiality and Privacy and Section 11.17, Data Handling and Record 
Keeping, for further information on future use of study records. 
11.15 Clinical Monitoring 
As per ICH-GCP 5.18 and FDA 21 CFR 312.50 clinical protocols are required to be adequately 
monitored by the study Sponsor. Clinical site monitoring is conducted to ensure that the rights 
and well-being of trial participants are protected, that the reported trial data are accurate, 
complete, and verifiable, and that the conduct of the trial is in compliance with the currently 
approved protocol/amendment(s), with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP), and with applicable regulatory requirement(s). 
Independent Data Monitor: 
Data monitors will visit sites in-person or using remote telepresence with the following visit 
objectives: 
• 
to verify the existence of signed research informed consent form and documentation of the 
informed consent process for each monitored subject; 
• 
to verify the prompt and accurate recording of all monitored data points, and prompt 
reporting of all SAEs; 
• 
to compare abstracted information with individual subjects’ records and source documents 
(subjects’ charts, laboratory analyses and test results, physicians’ progress notes, nurses’ 
notes, and any other relevant original subject information); and 
• 
to help ensure investigators are in compliance with the protocol. 
The monitors also will inspect the clinical site regulatory files to ensure that regulatory 
requirements (Office for Human Research Protections, OHRP), FDA and applicable guidelines 
(ICH-GCP) are being followed. During the monitoring visits, the site Principal Investigator 
(and/or designee) and other study personnel will be available to discuss the study progress and 

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monitoring visit. The site Principal Investigator (and/or designee) will make study documents 
(e.g., consent forms and pertinent electronic and/or paper medical records readily available for 
inspection by the IRB, the FDA, the site monitors, and the NIH staff for confirmation of the 
study findings. 
Schedule of Monitoring Activities 
Monitoring visits will be conducted after the first subject is treated and returns for 30-day 
follow up. Remote monitoring visits will conducted wherever possible using remote access to 
electronic medical records, transmitted source documents, associated emails, and monitoring 
reports. Electronic data queries from the Sponsor to the study site must be resolved within 7 
days of site notification. 
Extent of monitoring activities 
The monitors will provide 100% source-data verification of case report forms including adverse 
event reports. 
Routine independent audits will not be conducted.  
NIH Principal Investigator Monitoring: 
Accrual and safety will be monitored by the NIH Principal Investigator, seeking unusual or 
unexpected events, morbidity, or mortality. 
Institutional Review Board (IRB) of Record: 
Accrual and safety data will be monitored and reviewed annually by the Reviewing IRB  
(Advarra) Prior to implementation of this study, the protocol, and subject research consents will 
be reviewed and approved according to Protection of Human Subjects Research Title 45 CFR 
Part 46 of the Code of Federal Regulations (45 CFR 46).  Advarra must approve all amendments 
to the protocol or informed consent, and conduct continuing annual review so long as the 
protocol is open to accrual or follow up of subjects. 
Data and Safety Monitoring Board (DSMB) Monitoring 
DSMB activities are described in section 11.7 on page 53. 
11.16 Quality Assurance and Quality Control 
Quality assurance measures include 
- 
Diligent investigator procedure training in TELLTALE BASILICA-TAVR technique and 
device operation 
- 
Sponsor and investigator participation (when available) and review of TELLTALE 
BASILICA-TAVR procedures 
- 
Site initiation visit by NIH Principal Investigator, NIH Study Manager, and independent 
data monitors 
Quality control measures include 
- 
Site Principal Investigator review of completed case report forms 
- 
Study Manager review of case report forms with data clarification request reconciliation 

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- 
Data entry into an auditable electronic case report database 
- 
Independent data monitor source-data verification with data clarification request 
reconciliation 
- 
NIH Principal Investigator review of case report form data 
- 
Independent core lab review of imaging endpoints 
- 
Study Statistician review of case report form data. Errors will be corrected by 
investigators and data manager 
- 
Independent Clinical Events Adjudication committee adjudication of primary endpoints 
11.17 Data Handling and Record Keeping 
Clinical data (including adverse events (AEs), concomitant medications, and adverse reactions 
data) and clinical laboratory data will be entered into a 21 CFR Part 11-compliant data capture 
system provided by the study Sponsor. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. 
Case Report Form Completion 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The site investigators are responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 
All source document worksheets should be prepared in a neat, legible manner to ensure 
accurate interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document 
worksheets for recording data for each participant enrolled in the study. Data recorded in the 
electronic case report form (eCRF) derived from source documents should be consistent with 
the data recorded on the source documents. 
Case Report Forms (CRFs) will be completed for each study subject. It is the site Principal 
Investigator’s responsibility to ensure the accuracy, completeness, and timeliness of the data 
reported in the subject’s Case Report Forms. Source documentation supporting the Case Report 
Forms data should indicate the subject’s participation in the study and should document the 
dates and details of study procedures, AEs, and subject status. Sample Case Report Forms are 
provided in (APPENDIX A: Sample Case Report Forms). 
The site Principal Investigator or designated representative, should complete the Case Report 
Forms screens as soon as possible after information is collected, preferably on the same day 
that a study subject is seen for an examination, treatment, or any other study procedure but no 
more than 5 days post procedure. An explanation should be given for all missing data. 
Direct Access to Source Data 
Site investigators will follow Sponsor monitoring and auditing procedures to assure compliance 
with GCP guidelines. 

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The site Principal Investigator will grant monitor(s) and auditor(s) from the Sponsor or its 
designee and regulatory authority (ies) access to the subject’s original medical records for 
verification of data gathered on the CRFs and to audit the data collection process. The subject’s 
confidentiality will be maintained and will not be made publicly available to the extent 
permitted by the applicable laws and regulations. 
Regulatory authorities, the IRB and other appropriate institutional regulatory bodies, and/or 
the Sponsor may request access to all source documents, CRFs, and other study documentation 
for on-site audit or inspection. Direct access to these documents must be guaranteed by the 
site Principal Investigator, who must provide support at all times for these activities. 
Data transmission and storage 
Medical records source documents will be copied and transmitted electronically to the study 
Sponsor representative. 
These documents will include the entire electronic health record for the inpatient TELLTALE 
BASILICA-TAVR encounter. They also will include the physician notes for all baseline and follow-
up visits, and site interpretations of all relevant medical imaging examinations. 
Source documents also include the following medical imaging data in DICOM format. These are 
collected as obtained both for clinical and/or research purposes. They include cardiac 
catheterization fluoroscopy images, echocardiography, cardiac CT, cardiac MRI, and chest 
radiographs. These all will retain patient identifiers. Examinations performed for clinical 
evaluation prior to signing informed consent may be used as the baseline images. 
As indicated in section 11.13 (confidentiality): 
medical records will be transmitted and stored as source documents and will retain 
patient names and/or medical record numbers, to allow physician-investigators to 
recommend medical therapies as appropriate, to avoid risk of mis-identification. 
Imaging data will be transmitted electronically to the NIH for central laboratory analysis. 
Imaging data will be transmitted via secure file transfer mechanisms abiding FIPS 140-2, HIPAA 
and local institutional standards (such as https://nih.box.com or Nuance Powershare). Imaging 
data are stored in a secure Picture Archive Computer System (PACS) or vendor-neutral archive, 
according to local institutional standards. 
11.18 Study Records Retention 
The site Principal Investigator will maintain all study records according to ICH-GCP and 
applicable regulatory requirement(s). Records will be retained for at least 2 years following 
marketing application approval or 2 years after formal discontinuation of the clinical 
development of the investigational product or according to applicable regulatory 
requirement(s). If the site Principal Investigator withdraws from the responsibility of keeping 
the study records, custody must be transferred to a person willing to accept the responsibility. 
The Sponsor must be notified in writing if a custodial change occurs. 

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11.19 Collaborative Agreements 
This protocol will be conducted under a Clinical Trials Cooperative Research and Development 
Agreement between NHLBI and Transmural Systems, (date pending). 
11.20 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in 
the design and conduct of this trial. The study leadership in conjunction with the NHLBI has 
established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of 
interest. 
12 ABBREVIATIONS 
ADE 
Adverse device effect  
AE 
Adverse Event 
AR 
Aortic valve regurgitation 
AS 
Aortic valve stenosis 
BASILICA 
Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent 
Iatrogenic Coronary Artery obstruction 
CI 
Confidence Interval 
CRF 
Case Report Form 
CT 
Computed tomography 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
HRPP 
(NIH) Human Research Protection Program 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
MACE 
Major adverse clinical events 
mRS 
Modified Rankin Scale of stroke disability 
NHLBI 
National Heart Lung and Blood Institute 
NIH 
National Institutes of Health 
OHSRP 
NIH Office of Human Subjects Research Protections 
PI 
Principal Investigator 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
TAVR 
Transcatheter aortic valve implantation 

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TEE 
Transesophageal echocardiography 
TELLTALE 
Transmural Electrosurgery LeafLet Traversal And Laceration Evaluation device 
THV 
Transcatheter heart valve 
TTE 
Transthoracic echocardiography 
UADE 
Unanticipated adverse device effect 
UP 
Unanticipated problem 
VARC 
Valve academic research consortium (criteria) 
VTC 
Virtual transcatheter Valve-To-Coronary distance 
VTS 
Virtual transcatheter Valve-To-Sinotubular-junction distance 
 
 
 

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13 APPENDIX A: Sample Case Report Forms 
 
 

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14 Appendix B: Reporting Obligations 
14.1 Reporting obligations of NIH Principal Investigator 
Reports from NIH PI 
Submission or event 
 
Reporting Time Frame 
Regulatory 
Body 
Current Investigator list 
Every 6 months 
FDA 
IDE Progress Report or  
Continuing Review 
Annual 
FDA; IRB 
Deviations from the investigational plan 
(emergency) 
Within 5 working days 
IRB; FDA 
Unanticipated Adverse Device Effects (UADE) 
As soon as possible but within 10 
working days. 
Within 7 calendar days  
FDA; 
IRB; CD 
Anticipated Adverse Device effect (ADE) 
Annual summary 
FDA; IRB 
Serious Adverse Events (SAE-not directly related to 
the device) 
Annual progress report; 
Within 14 calendar days (CD) 
IRB; FDA 
CD 
Adverse Events 
Annual summary 
IRB; FDA 
Death of a research subject at least possibly 
related to research 
Within 24 hours 
IRB; CD 
Death unlikely or unrelated to research 
At continuing review 
Report within 7 calendar days (CD) 
IRB; FDA 
CD 
Unanticipated Problems (UP) involving subject risk 
Within 7 calendar days  
IRB; CD 
Major Protocol Deviations (PD) 
Within 7 calendar days 
Annual progress report 
IRB; CD 
FDA 
Minor Protocol Deviations (PD) 
Annual progress report; 
Within 14 days(CD) 
FDA; IRB 
CD 
Serious or Continuing Non-compliance 
Within 7 calendar days  
IRB; CD 
Use of a device without obtaining informed 
consent 
Within 5 working days  
FDA 
Withdrawal of IRB approval 
Within 5 working days 
FDA; All 
PIs 
Withdrawal of FDA approval 
Within 5 working days 
All PIs; IRB 
New information that might affect willingness of 
subjects to enroll or continue participation 
Within 7 calendar days 
IRB; CD 
Recall and Device disposition 
Within 30 working days 
All PIs; IRB; 
FDA 
Sponsor suspend or terminate protocol 
Within 7 calendar days 
All PIs; IRB; 
FDA 
Final Report (enrollment complete & termination) 
Within 30 working days 
(termination) 
Within 6 months (final report) 
FDA 
Abbreviations: CD = NHLBI Clinical Director.  FDA = United States Food and Drug Administration; 
IRB = Institutional Review Board; PI = NIH Principal Investigator / Sponsor Representative 
All other adverse events are reported collectively at time of IRB continuing review. 

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14.2 Reporting obligations of Enrolling Site Principal Investigator to the Sponsor* 
* In addition to reporting to the Sponsor, the Site Principal Investigator is responsible for further 
reporting of events to their own institution per local reporting requirements and to Advarra (see 
Advarra IRB Handbook). 
15 VERSIONS 
Version 
Revision 
2022-11-30 
First FDA approved version 
2023-05-25 
• Increase number of sites from 10 to 15 
• More-conservative stopping rules, as stipulated by DSMB 
• More-focused reporting of abnormal blood tests as adverse events 
• Clarification that only one post-TAVR troponin measurement is required, 
to resolve inconsistency between section 2.4 text and Schedule of 
Activities 
• Reference to upcoming IFU revisions for possible alternative guiding 
catheters 
• Telephone/electronic consent allowed, for screening only 
• Housekeeping, list additional exploratory endpoints 
• Additional recipient of anonymized research data  
• Additional/optional imaging exams (coronary arteriography and CT) if 
obtained in the course of standard medical care are transmitted to NHLBI 
for analysis. 
• Lengthened allowable window for baseline CT scan 
Site PI Obligation: Submission or event 
Reporting Time Frame 
Recipient 
Deviations from the investigational plan 
(emergency) 
Immediately, but no later than 3 working 
days 
Sponsor 
Unanticipated Adverse Device Effects (UADE) 
Immediately, but no later than 7  
calendar days 
Sponsor 
Serious Anticipated Adverse Device Effect (SADE) Within 3 working days 
Sponsor 
Anticipated Adverse Device effect (ADE) 
Within 7 working days 
Sponsor 
Serious Adverse Events (SAE-not directly related 
to the device) 
Within 5 working days 
Sponsor 
Adverse Events (AE) 
Within 7 working days 
Sponsor 
Death unlikely or unrelated to research  
Immediately but within 3 working days 
Sponsor 
Death of a research subject at least possibly 
related to research 
Within 24 hours 
Sponsor 
Unanticipated Problems (UP) involving subject 
risk 
Within 3 working days 
Sponsor 
Major Protocol Deviations (PD) 
Within 3 working days 
 
Sponsor 
Minor Protocol Deviations (PD) 
Within 7 working days 
Sponsor 
Non-compliance, Serious 
Within 3 working days 
 
Sponsor 
Non-compliance, Continuing 
Within 3 days working days 
Sponsor 

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• Updated background on global reported clinical experience 
• Clarify CEAC endpoint review covers only 30d data, when primary and 
secondary endpoints assessments are due 
2023-10-01 
• Study expansion to 15 additional subjects with native aortic valve failure, 
after initial enrollment quota of 15 is met, in coordination with CDRH. 
• Clarify ongoing proctorship may be offered in-person or via telepresence, 
and other housekeeping changes. 
2024-10-31 
• Increase number of candidates allowed to be screened, to 180 (should 
have been requested with Amendment B)  
 
 
 

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16 REFERENCES 
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Jaegere PP, del Valle R, Chiam PT, Moreno R, Pradas G, Ruel M, Salgado-Fernandez J, 
Sarmento-Leite R, Toeg HD, Velianou JL, Zajarias A, Babaliaros V, Cura F, Dager AE, 
Manoharan G, Lerakis S, Pichard AD, Radhakrishnan S, Perin MA, Dumont E, Larose E, 
Pasian SG, Nombela-Franco L, Urena M, Tuzcu EM, Leon MB, Amat-Santos IJ, Leipsic J, 
Rodes-Cabau J, Predictive factors, management, and clinical outcomes of coronary 
obstruction following transcatheter aortic valve implantation: insights from a large 
multicenter registry. J Am Coll Cardiol, 2013;62(17):1552. [PMID: 23954337] 
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Ribeiro HB, Rodes-Cabau J, Blanke P, Leipsic J, Kwan Park J, Bapat V, Makkar R, Simonato 
M, Barbanti M, Schofer J, Bleiziffer S, Latib A, Hildick-Smith D, Presbitero P, Windecker S, 
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