Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Latrogenic Coronary Artery Obstruction (BASILICA)
Phase: NA
Conditions: Native and Valve in Valve Aortic Valve Failure
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

BASILICA prospective investigation 
Page 1 of 39 
2018-03-09 
Protocol Title: 
Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruc-
tion (BASILICA) prospective investigation  
Version History 
2017-08-07 
IDE application after NHLBI Branch Review 
2017-10-03 
NHLBI Scientific Review 
2017-11-13 
NHLBI IRB Stipulations 
2018-03-09 
Add site 
Investigational Device Exemption (IDE) 
G170201 Pending 
NIH IRB Number              NCT Number
18-H-N018                     NCT03381989
IDE Sponsor-Investigator: 
Robert J. Lederman, MD, Senior Investigator, NHLBI Division of Intramural Research 
Key Roles 
Role 
Individual 
Affiliation 
FWA If ap-
plicable 
Accountable Investigator 
(NIH) 
Robert J. Lederman, MD 
NHLBI DIR 
00005897 
Lead Investigator (NIH) 
Jaffar M. Khan, BM BCh 
NHLBI DIR 
National Co-Principal In-
vestigators 
Danny Dvir, MD 
Adam B. Greenbaum, MD 
Vasilis C. Babaliaros, MD 
Toby Rogers, PhD, BM BCh 
Susheel Kodali, MD 
University of Washington, Seattle 
Henry Ford Hospital 
Emory University Hospital 
Medstar Washington Hospital Center 
Columbia University Medical Center/NewYork 
Presbyterian Hospital 
Study Manager 
Annette M. Stine, RN 
NHLBI DIR 
CT and angiography core 
lab 
Marcus Y. Chen, MD 
NHLBI DIR 
Independent monitoring 
service 
TBD 
TBD 

BASILICA prospective investigation 
Page 2 of 39 
2018-03-09 
Independent Clinical 
Events Adjudication Com-
mittee 
TBD 
TBD 
 
Data Safety Monitoring 
Board 
 
 
Jamieson M. Bourque, MD, 
MHS  
NHLBI  
University of Virginia 
 
IDE Study Sponsor 
 
 
Robert J. Lederman, MD, on 
behalf of NHLBI  
NHLBI DIR 
 
Data Coordinating Center Robert J. Lederman, MD 
NHLBI DIR 
00000004 
Study Statistician 
Xin Tian, PhD 
NHLBI Office of Biostatistics Research 
 
Site 1 PI 
Danny Dvir, MD 
University of Washington, Seattle, WA 
00006878 
Site 2 PI 
Adam B. Greenbaum, MD 
Henry Ford Hospital, Detroit, MI 
00005846 
Site 3 PI 
Vasilis C. Babaliaros, MD 
Emory University Hospital, Atlanta, GA 
00005792 
Site 4 PI 
Toby Rogers, PhD, BM BCh 
Medstar Washington Hospital Center, Wash-
ington, DC 
00000504 
Site 5 PI 
Susheel Kodali, MD 
Columbia University Medical Center/NewYork 
Presbyterian Hospital 
00002636 
Site 6 PI 
TBD 
 
 
 
* No subject enrollment 
Estimated Duration of Study: 
Participant duration: 1 year 
Analysis 1: year after enrollment is complete 
Total estimated study duration: 2 years 
Estimated Completion Date of Study: 
September 30, 2019 
Subjects of study and sites: 
 
DISCLOSURES 
The non-NIH investigators have the following conflicts of interest: 
Subjects 
Sex 
Age range 
Sites 
60 screened 
30 enrolled 
Men & Women  
≥21 years 
Up to 6 

BASILICA prospective investigation 
Page 3 of 39 
2018-03-09 
DD is a consultant Edwards Lifesciences, Medtronic, Abbott, and W.L. Gore. 
ABG serves as a proctor for Edwards Lifesciences and St Jude Medical.  
VCB is a consultant for Edwards Lifesciences and for Abbott Vascular, and his employer has research con-
tracts from Edwards Lifesciences, Abbott Vascular, Medtronic, St Jude Medical, and Boston Scientific. 
ABBREVIATIONS 
ADE 
Adverse device effect  
AR 
Aortic valve regurgitation 
AS 
Aortic valve stenosis 
CT 
Computed tomography 
BASILICA 
Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Cor-
onary Artery obstruction 
iFR 
Instantaneous wave-free Flow Reserve index  
LAMPOON 
Intentional Laceration of the Anterior Mitral leaflet to Prevent iatrogenic left ventricu-
lar Outflow tract ObstructiON after transcatheter mitral valve replacement 
MACE 
Major adverse clinical events 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
TAVR 
Transcatheter aortic valve implantation 
TEE 
Transesophageal echocardiography 
THV 
Transcatheter heart valve 
VARC 
Valve academic research consortium (criteria) 
UADE 
Unanticipated adverse device effect 
UP 
Unanticipated problem 
6MWT 
Six minute walking test 
KEYWORDS 
Transcatheter aortic valve replacement 
Valve-in-valve TAVR 
Coronary artery obstruction 
Bioprosthetic heart valve failure 
PRÉCIS 
Transcatheter aortic valve replacement (TAVR) is an option to treat aortic valve stenosis or failure of a sur-
gically implanted tissue valve.  Sometimes TAVR displaces the diseased aortic valve leaflets outwards, caus-
ing life-threatening obstruction of the coronary arteries that supply blood to the heart. This is more com-
mon in surgically implanted tissue valves that are designed to achieve the largest aortic valve orifice area.  
Despite attempts to protect the coronary arteries from obstruction in these patients using coronary stents, 
the mortality of TAVR-associated coronary artery obstruction remains prohibitively high. 
The investigators have developed and tested a technique to tear the existing aortic valve leaflet and enable 
TAVR in such patients. The procedure is called Bioprosthetic or native Aortic Scallop Intentional Laceration 
to prevent Iatrogenic Coronary Artery obstruction (BASILICA).  
The purpose of this study is to perform BASILICA in patients who have no good options to prevent coronary 
artery obstruction during TAVR. 

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Table of Contents 
1.0 
Protocol Summary ............................................................................................................................. 5 
2.0 
OBJECTIVE .......................................................................................................................................... 7 
3.0 
BACKGROUND ................................................................................................................................... 7 
4.0 
CLINICAL AND SCIENTIFIC JUSTIFICATION.......................................................................................... 7 
4.1 
Predictors of coronary artery obstruction after TAVR ...................................................... 8 
5.0 
TREATMENT OPTIONS ....................................................................................................................... 9 
6.0 
STUDY DESIGN ................................................................................................................................... 9 
6.1 
Schematic of Study Design ............................................................................................... 9 
6.2 
Overview of Study Design ................................................................................................. 9 
6.3 
Study Population ............................................................................................................ 10 
6.4 
BASILICA TAVR Procedure .............................................................................................. 10 
6.5 
Time and Events Schedule .............................................................................................. 11 
6.6 
Visit Schedule ................................................................................................................. 12 
6.7 
Milestones ...................................................................................................................... 15 
7.0 
ELIGIBILITY ASSESSMENT ................................................................................................................. 16 
7.1 
Inclusion Criteria ............................................................................................................. 16 
7.2 
Exclusion criteria ............................................................................................................ 16 
7.3 
Rationale for selection criteria ....................................................................................... 16 
8.0 
Strategies for Recruitment .............................................................................................................. 16 
9.0 
SAMPLE COLLECTION, STORAGE AND TRACKING PLAN ................................................................... 17 
10.0 
BIOSTATISTICAL AND ANALYTICAL CONSIDERATIONS ..................................................................... 17 
10.1 
Sample Size ..................................................................................................................... 17 
10.2 
Study Analysis ................................................................................................................. 17 
10.3 
Stopping Rules and Data Safety Monitoring ................................................................... 19 
10.4 
Off study criteria ............................................................................................................. 21 
11.0 
ADVERSE EVENT REPORTING ........................................................................................................... 22 
11.1 
Definitions ...................................................................................................................... 22 
11.2 
Adverse event management: ......................................................................................... 25 
12.0 
HUMAN SUBJECT PROTECTION ....................................................................................................... 27 
12.1 
Rationale for Subject Selection ....................................................................................... 27 
12.2 
Risks and Discomforts ..................................................................................................... 27 
13.0 
TEST ARTICLE ................................................................................................................................... 29 
13.1 
Asahi-Intecc Astato XS 20, 510(k) K103057 .................................................................... 29 
14.0 
INVESTIGATOR ADMINISTRATIVE REQUIREMENTS .......................................................................... 30 
14.1 
Good Clinical Practice ..................................................................................................... 30 
14.2 
IRB Submissions .............................................................................................................. 30 
14.3 
Subject Information and Informed Consent ................................................................... 30 
14.4 
Subject Confidentiality ................................................................................................... 31 
14.5 
Protocol Compliance ...................................................................................................... 31 
14.6 
Direct Access to Source Data .......................................................................................... 31 
14.7 
Case Report Form Completion ....................................................................................... 31 
14.8 
Record Retention ............................................................................................................ 32 
14.9 
Publication and Presentation of Study Findings and Use of Information ....................... 32 
14.10 
Study Eligibility Committee ............................................................................................. 32 
15.0 
SPONSOR REGULATORY REQUIREMENTS ........................................................................................ 32 
15.1 
Role of Sponsor .............................................................................................................. 32 
15.2 
General Duties ................................................................................................................ 32 

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2018-03-09 
15.3 
Monitoring ...................................................................................................................... 32 
15.4 
Site Selection and Training ............................................................................................. 33 
REFERENCES ................................................................................................................................................... 34 
APPENDIX A: Risk Analysis .............................................................................................................................. 36 
APPENDIX B: Tensile strength implications of bedside modification of Astato XS 20 guidewire .................... 39 
 
1.0 Protocol Summary 
Title: 
Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatro-
genic Coronary Artery obstruction (BASILICA) prospective investigation 
Précis: 
Transcatheter aortic valve replacement (TAVR) is an option to treat aortic 
valve stenosis or failure of a surgically implanted tissue valve.  Sometimes 
TAVR displaces the diseased aortic valve leaflets outwards, causing life-
threatening obstruction of the coronary arteries that supply blood to the 
heart. This is more common in surgically implanted tissue valves that are de-
signed to achieve the largest aortic valve orifice area.  Despite attempts to 
protect the coronary arteries from obstruction in these patients using coro-
nary stents, the mortality of TAVR-associated coronary artery obstruction re-
mains prohibitively high. 
The investigators have developed and tested a technique to split the existing 
aortic valve leaflet and enable TAVR in such patients. The procedure is called 
Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatro-
genic Coronary Artery obstruction (BASILICA).  
The purpose of this study is to perform BASILICA in patients who have no 
good options to prevent coronary artery obstruction during TAVR. 
Hypothesis: 
BASILICA avoids life-threatening coronary artery obstruction in at-risk pa-
tients during TAVR 
Specific Aims 
Specific aim 1: To determine early multi-center feasibility of BASILICA 
Specific aim 2: To determine provisional feasibility of BASILICA (Freedom 
from MACE to hospital discharge and 30days)  
Primary Safety Endpoint 
Freedom from MACE (according to VARC-2) at 30 days 
Primary Feasibility End-
points 
Procedure clinical success (defined below) 
Study Population: 
Patients with bioprosthetic aortic valve failure or native aortic valve stenosis 
at high risk of coronary artery obstruction from leaflet displacement during 
TAVR 

BASILICA prospective investigation 
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2018-03-09 
Inclusion Criteria 
Adults age ≥ 21 years 
High or extreme risk of surgical aortic valve replacement according to the lo-
cal multidisciplinary heart team 
Undergoing TAVR for valve-in-valve failure or native aortic stenosis (“on-la-
bel” TAVR) 
Deemed likely to suffer coronary artery obstruction from TAVR according to 
multidisciplinary heart team 
Concurrence of the study eligibility committee 
Exclusion Criteria 
Does not consent to participate 
Excessive target aortic leaflet calcification or masses on baseline CT 
Survival despite successful procedure expected < 12 months 
Subjects unwilling to participate or unwilling to return for study follow-up ac-
tivities.  
Pregnancy or intent to become pregnant prior to completion of all protocol 
follow-up procedures 
Phase: 
Pilot 
Study Procedure 
NHLBI Data Coordinating Center 
NHLBI + Local Institutional Review Boards 
Sites are trained by national PIs and NHLBI investigators 
Subjects are identified by site investigators 
Baseline and follow-up CT and fluoroscopy are analyzed by core laboratory 
Subject eligibility is confirmed by local multidisciplinary heart team including 
cardiac surgery, and is confirmed by study eligibility committee 
Subjects are enrolled prospectively 
Primary analysis based on 30-day outcomes; Secondary analysis includes 12-
month outcomes 
Sample Size 
30 subjects at up to 6 sites 
Risk-benefit determination These patients have few or no therapeutic alternatives and have the poten-
tial to benefit from this procedure 
Number of Sites enrolling 
participants: 
6 
Study Duration: 
Two years  
Participant Duration: 
One year 

BASILICA prospective investigation 
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2018-03-09 
2.0 OBJECTIVE 
The objective of this protocol is further to characterize the feasibility and safety of Bioprosthetic or native 
Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction (BASILICA), in pa-
tients at high risk of coronary artery obstruction complicating TAVR. 
In this protocol, we use transcatheter heart valves (THV) according to their marketed indication, on-label. 
3.0 BACKGROUND 
Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replace-
ment in intermediate and high-risk patients.  TAVR is also an effective treatment for failure of bioprosthetic 
surgical aortic valves, a treatment known as valve-in-valve TAVR. Valve-in-valve TAVR is associated with low 
mortality, satisfactory hemodynamics, and good intermediate-term func-
tional outcomes in selected high risk patients [1, 2].  Valve-in-valve TAVR 
commonly exacerbates valve under-sizing (a phenomenon known as pa-
tient-prosthetic mismatch), which increases one-year mortality [1, 2].   
Coronary artery obstruction is a devastating complication of valve-in-valve 
TAVR with a greater than 50% mortality [3].  Coronary artery obstruction 
occurs when the transcatheter heart valve displaces the underlying surgical 
or native aortic valve leaflets outwards and obstructs the coronary artery 
ostia, usually by sealing the sinus of Valsalva at the sinotubular junction 
(Figure 1). Coronary artery obstruction occurs most commonly during TAVR 
for surgical bioprothesis designs intended to maximize effective aortic ori-
fice area (“stented” bioprostheses that have externally mounted leaflets, 
and “stentless” surgical bioprostheses). Coronary artery obstruction can be 
predicted by pre-procedure morphology and CT.   
4.0 CLINICAL AND SCIENTIFIC JUSTIFICATION 
We propose a solution based on our non-clinical [5] and initial clinical [6] 
LAMPOON procedure (intentional catheter-based traversal and laceration 
a mitral valve leaflet structure in order to prevent the complications of 
leaflet displacement after related transcatheter mitral valve implantation).  
In LAMPOON, we use catheter techniques to split the mitral valve leaflet to 
prevent obstruction of the left ventricular outflow tract.   
 
Figure 1. Coronary artery obstruction a

BASILICA prospective investigation 
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2018-03-09 
Using a simple modification of the LAMPOON technique, we have developed a technique to split an aortic 
valve leaflet, whether bioprosthetic or native, to prevent coronary artery obstruction after TAVR.  The new 
technique is called Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery 
obstruction (BASILICA). Figure 2 shows a representative BASILICA TAVR procedure. 
To date, seven patients have undergone compassionate BASILICA to enable TAVR. All survived to discharge 
without major adverse events.  
4.1 Predictors of coronary artery obstruction after TAVR 
Table 1 lists anatomic and artificial valve factors thought to contribute to the risk of coronary artery ob-
struction during TAVR.  Many of these are continuous parameters and are thought to interact with each 
other, such as narrow and short sinuses of Valsalva. One of the most powerful predictors is thought to be a 
small “virtual tube to coronary artery distance (VTC)”, especially when less than 3-4mm[3, 7].  However, 
the risk determination must integrate all of these factors, and must incorporate judgement.  
Table 1. Predictors of coronary artery obstruction after TAVR, expanded from Dvir [7] and Riberio[3] 
Anatomic factors 
 
Narrow virtual transcatheter heart valve to coronary distance (VTC): 
<4mm* 
Low-lying coronary ostia 
Narrow sinotubular junction 
Low sinus of Valsalva height 
Narrow sinuses of Valsalva * 
Previous root repair (eg, root graft and coronary reimplantation) 
Bioprosthetic valve factors 
Internal stent frame with external leaflets (eg, Mitroflow, Trifecta)* 
No stent frame (homograft, stentless valves)* 
Long or thick or bulky bioprosthetic leaflets 
Supra-annular position 
 
Figure 2. A represent BASILICA TAVR procedure. A: An electrified crossing wire (1) traverses the level of a bioprosthetic 
valve frame (2). B: The electrified shaft of the BASILICA guidewire is splitting the left coronary scallop of the intended 
aortic valve (3).  C: After successful BASILICA, a Sapien 3 TAVR valve is implanted and coronary arteriography demon-
strates patency of the left coronary artery ostium. 
1
2
A
C
B
3
4

BASILICA prospective investigation 
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2018-03-09 
Stent posts that extend beyond sinotubular junction 
Intended overexpansion/fracture of bioprosthetic valve frame during TAVR 
Transcatheter valve fac-
tors 
Extended sealing cuff 
High implantation 
* Independent predictor of coronary obstruction in one retrospective registry [3]
5.0 TREATMENT OPTIONS
Candidates for TAVR with BASILICA have no good alternative treatment options.  They are not eligible for 
definitive treatment using surgical aortic valve repair or replacement.  Despite pre-positioning of bailout 
coronary stent delivery systems before TAVR, the outcome of TAVR-induced coronary artery obstruction is 
catastrophic with a mortality > 50% [3]. 
6.0 STUDY DESIGN 
6.1 Schematic of Study Design 
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 CT 
(if feasible)
TAVR with BASILICA
30-day follow-up with
CT (if not pre-
discharge) and echo
12 month follow-up 
with CT, echo, and 
termination visit
6.2 Overview of Study Design 
This is a prospective, open-label, single-arm, multi-center, investigator-initiated, independently-adjudicated 
trial of BASILICA immediately before TAVR in subjects at high risk of coronary artery obstruction. 

BASILICA prospective investigation 
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2018-03-09 
Candidates will be identified by the participating structural heart disease programs.  In evaluation of aortic 
valve disease, candidates will undergo clinical evaluation, echocardiography, 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.  They will undergo endpoint as-
sessment before discharge, after 30 days, and then 12 months. 
6.3 Study Population 
Subjects are undergoing planned TAVR because of high or prohibitive risk of surgical aortic valve replace-
ment for bioprosthetic aortic valve failure or native aortic valve stenosis.  The subjects are deemed to have 
excessive risk of TAVR-induced coronary artery obstruction based on features enumerated in Table 1 in 
section 4.1. 
6.4 BASILICA TAVR Procedure 
The 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 landing zone, and predict 
post-TAVR coronary obstruction related leaflet encroachment on the sinotubular junction and coronary ar-
tery 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 BASILICA procedure has three steps: (1) leaflet traversal with a guidewire, 
followed by (2) leaflet laceration, immediately followed by (3) TAVR.  These are all guided by fluoroscopy 
and adjunctive echocardiography as needed. 
Research study participation is defined as beginning the moment BASILICA traversal is attempted. 
First catheter access is obtained typically via four arterial introducer sheaths (two for BASILICA, one for he-
modynamics and angiography, and one for TAVR) and at least one venous introducer sheaths for tempo-
rary transvenous pacing.  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 re-
spectively.  Care is taken to avoid entrapment of mitral valvular structures. A snare catheter is positioned in 
the LVOT.  A coaxial traversal guiding catheter system (typically tandem catheters) directs electrosurgery 
devices (typically a rigid 0.014” guidewire inside a polymer jacket wire convertor) against the base of the 
coronary cusp targeted for laceration, using fluoroscopic and/or echocardiographic guidance.   
Traversal is accomplished by transcatheter electrosurgery by connecting the back end of the 0.014” guide-
wire to an electrosurgery pencil during short bursts of “pure, cutting” radiofrequency energy at approxi-
mately 30W.  The guidewire is repositioned as needed until it crosses the aortic leaflet and is snare-re-
trieved and externalized. Nonionic conductive flush (dextrose 5%) can be administered as needed via the 
guiding catheters to reduce guidewire char and thromboembolism. 

BASILICA prospective investigation 
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2018-03-09 
Next the polymer jacket wire convertor is withdrawn, and the traversal wire is modified by the operator by 
(1) denuding a non-circumferential segment ~2mm in length, 90o arc and (2) kinking the denuded segment 
to enforce its position at the inner curvature of the intended guidewire lacerating surface.  Next the poly-
mer jacket radiopaque marker tip is locked adjacent to the kinked denuded shaft segment.  Next the en-
snared guidewire is externalized to position the lacerating surface across the base of the leaflet. 
BASILICA may be performed on one or two valve leaflets that may threaten coronary artery obstruction. 
Next, at operator discretion, the transcatheter heart valve may be positioned before or after the laceration 
step.  If before, the operator assures no entrapment of the TAVR system with the laceration system of cath-
eters. 
At operator discretion, stroke prevention strategies may be employed, including external carotid artery 
compression and intravascular embolic protection devices. 
Laceration is performed by positioning the laceration surface along the intended leaflet base, and applying 
tension on both free ends of the guidewire while simultaneously apply electrosurgery energy (typically 
70W) in short bursts, until the laceration is complete and the guidewire is free. 
Hemodynamics are recorded quickly after laceration before TAVR.  Coronary artery stent systems are posi-
tioned prophylactically at the discretion of the operator.  Predilatation, including intentional disruption of 
the bioprosthetic valve frame, is performed at operator discretion, before or after TAVR. Then TAVR is per-
formed 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 opera-
tor discretion to achieve an optimum TAVR result.  Coronary artery patency is established using angi-
ography and, if employed, using prepositioned pressure-tip guidewires.  Coronary artery pressure (instanta-
neous wave-free ratio, iFR) may further be examined if possible at the discretion of the operator. 
Completion hemodynamics and echocardiography are recorded.   Finally, percutaneous femoral artery and 
vein vascular hemostasis is obtained and the subject convalesces in the appropriate inpatient recovery unit. 
Before discharge, follow-up transthoracic echocardiography is recorded.   A single contrast-enhanced CT of 
the heart is obtained before discharge if renal function allows, otherwise it is deferred as long as 30-days. 
Blood tests are recorded for research only as obtained for medical care. 
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 postmarketing TAVR registry. 
6.5 Time and Events Schedule 
 
Screening 
Baseline 
Day 0 
Inpatient 
30 d (±14d) FU 
12 mo (± 4 wk) 
(range) FU
Baseline informed consent: 
 
X 
 
 
 
 
Multidisciplinary heart team eligibility determina-
tion 
 
X 
 
 
 
 

BASILICA prospective investigation 
Page 12 of 39 
2018-03-09 
 
Screening 
Baseline 
Day 0 
Inpatient 
30 d (±14d) FU 
12 mo (± 4 wk) 
(range) FU
Baseline clinical assessment 
 
X 
 
 
 
 
NYHA Classification 
 
X 
 
 
 
X 
Blood tests: CBC, Platelet, Haptoglobin, Liver panel, 
Chemistry Panel, Albumin, LDH, BNP/Pro-BNP, Tro-
ponin that are obtained for medical care are cap-
tured for research.  Pregnancy test if applicable be-
fore day 0 and before research CT 
 
X 
 
X 
X 
X 
Vital signs and in-person visit 
 
X 
 
 
X 
X 
Cardiac CT contrast-enhanced gated dynamic 
Screening or 
baseline 
Screening or 
baseline 
 
Inpatient or 
30D 
Inpatient or 
30D 
 
BASILICA assisted TAVR 
Enrollment begins once attempted 
 
 
X 
 
 
 
Echocardiogram, surface or transesophageal 
Screening or 
baseline 
Screening or 
baseline 
X 
 
X 
X 
Adverse event assessment 
 
 
X 
X 
X 
X 
Data capture from TVT-registry surveillance: KCCQ-
12, baseline-only frailty 
 
X 
 
 
X 
X 
Subjects would receive continuing care from their primary physicians with consultant input as requested 
from the structural heart disease program. 
For subjects who die, necropsy evaluation is requested to examine the heart at NIH. 
6.6 Visit Schedule 
All activities except TAVR/BASILICA, Consent, KCCQ, and Adverse event assessment are performed for standard clinical 
care. 
Timing 
Event 
Screening (any time) 
Medical, Surgical and Interventional Assessment, determination and docu-
mentation that the subject has no other options for TAVR 
Screening (any time) 
Cardiac CT contrast enhanced, gated dynamic 
Screening (any time) 
Echocardiogram, transesophageal or surface 
Screening (any time) 
Multidisciplinary heart team eligibility determination and documentation 
Baseline (within 30 days of 
procedure) 
Research Informed Consent to include documented Inclusion and Exclusion 
criteria 

BASILICA prospective investigation 
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2018-03-09 
Baseline (within 30 days of 
procedure) 
Clinical Assessment to include: 
• 
Vital signs 
• 
Baseline symptoms 
• 
NYHA Classification 
• 
Other co-morbidities that could preclude the subject living the re-
quired 12 months post procedure 
• 
Surface echocardiogram-transthoracic and/or transesophageal 
• 
TVTRegistry quality surveillance data, including QOL, Frailty 
Clinical Blood tests if obtained are captured for research 
• 
CBC 
• 
Platelets 
• 
Haptoglobin 
• 
Liver Function panel 
• 
Chemistry panel 
• 
Troponin 
• 
Albumin 
• 
LDH 
• 
BNP/Pro-BNP 
• 
Pregnancy test if applicable 
Day 0 
TAVR with BASILICA procedure attempted, which marks enrollment.  
Subjects who do not proceed to BASILICA attempts are recorded as screen 
failures, and the reason is recorded. 
Pre-discharge  
Clinical Evaluation to include:  
• 
Cardiac CT scan contrast enhance, gated dynamic- if not clinically 
suitable then re-schedule for 30 Day follow up visit 
• 
Surface echocardiogram and/or transesophageal 
• 
Adverse Event Assessment 
Clinical Blood tests if obtained are captured for research 
• 
CBC 
• 
Platelets 
• 
Haptoglobin 
• 
Liver Function panel 
• 
Chemistry panel 
• 
Troponin 
• 
Albumin 
• 
LDH 
• 
BNP/Pro-BNP 
Pregnancy test if applicable 

BASILICA prospective investigation 
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2018-03-09 
30-day (±14 days) 
Clinic/office visit to update subject’s vital status to include: 
• 
Vital signs 
• 
ECG 
• 
Medication Assessment 
• 
NYHA Classification 
• 
Surface Echocardiogram and/or transesophageal 
• 
Cardiac CT scan contrast enhanced, gated dynamic if not conducted 
pre-discharge for clinical reasons 
• 
Clinical blood work is captured for research including: 
CBC with platelets 
Haptoglobin 
Chemistry Panel 
PT INR 
BNP/Pro-BNP 
• 
TVTRegistry quality surveillance data, including QOL  
• 
Adverse Event Assessment 
12 month (±30 days) 
Clinic/office visit to update subject’s vital status to include: 
• 
Vital signs 
• 
Medication Assessment 
• 
NYHA Classification 
• 
Surface Echocardiogram and/or transesophageal 
• 
Clinical blood work is captured for research including: 
CBC with platelets 
Haptoglobin  
Chemistry Panel 
PT INR 
BNP/Pro-BNP 
• 
TVTRegistry quality surveillance data, including QOL 
• 
Adverse Event Assessment 
 

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2018-03-09 
6.7 Milestones 
 
This section is submitted to comply with recent NIH IRP initiatives. Should a milestone not be met, all milestones will 
be shifted in time until the protocol is complete within the predicted protocol completion timeline.   
- 
Milestone one: Regulatory phase 
Regulatory approval including scientific and ethics review, at NIH and at participating sites, and FDA review, is ex-
pected to be complete by October 1 2017. 
- 
Milestone two: Contracting phase 
NIH contracts for services including clinical events adjudication are expected to be complete by October 1 2017. 
- 
Milestone three: Site initiation 
Site selection, training, and initiation is expected to be complete before November 1 2017. 
- 
Milestone four: Enrollment 
First patient should be enrolled 30 days from the initiation of the first site.  Should this not occur, then the 30 day 
period will be extended.  Enrollment should be completed within 12 months. We expect the tempo of enrollment to 
increase over time as additional sites and experience accrue. 
Continuing reviews to IRB, DSMB, and FDA will be performed during this period. 
- 
Milestone five: Follow-up and reporting 
After the last patient is enrolled, follow-up is performed for 12 months.  The study phase is changed from recruit-
ment to follow-up and to analysis, as appropriate. We expect the primary manuscript to be prepared based on data 
from 30 day follow-up.  We expect the final analysis to be complete within 12 months after follow-up is complete. 
8/1/2017
9/20/2017
11/9/2017
12/29/2017
2/17/2018
4/8/2018
5/28/2018
7/17/2018
9/5/2018
10/25/2018
FU & Reporting
Enrollment
Site initiation
Contracting
Regulatory

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2018-03-09 
7.0 ELIGIBILITY ASSESSMENT 
7.1 Inclusion Criteria  
• 
Adults age ≥ 21 years 
• 
High or extreme risk of surgical aortic valve replacement according to the local multidisciplinary 
heart team 
• 
Undergoing TAVR for valve-in-valve or native aortic valve failure (“on-label” TAVR) 
• 
Deemed likely to suffer coronary artery obstruction from TAVR according to multidisciplinary heart 
team 
• 
Concurrence of the study eligibility committee 
7.2 Exclusion criteria 
• 
Subjects unable to consent to participate, unless the subject has a legally authorized representative  
• 
Excessive target aortic leaflet calcification or masses on baseline CT 
• 
Survival despite successful procedure expected < 12 months 
• 
Planned concurrent valve intervention in the same setting (such as transcatheter mitral valve ther-
apy or paravalvular leak therapy) 
• 
Subjects unwilling to participate or unwilling to return for study follow-up activities.  
• 
Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures 
7.3 Rationale for selection criteria 
The selection criteria allow enrollment of the intended population with little anticipated selection bias. In-
stead of functional or geometric selection criteria, the study will enroll all subjects deemed otherwise suita-
ble for TAVR yet at risk of the problem to be addressed by BASILICA, the investigational procedure.  
There are no validated prediction models for coronary artery obstruction. Features predictive of coronary 
obstruction will be specifically outlined to the heart team and to the study eligibility committee and cap-
tured in the data collection form. 
Subjects are eligible if BASILICA laceration is contemplated for one or for two threatened coronary arteries. 
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.  
Composition of the study eligibility committee is described in section 14.10. 
8.0 Strategies for Recruitment  
Subjects will be recruited from the Structural Heart Disease clinical programs of the participating hospitals.   
The distribution of planned enrolling sites assures accessibility of the trial to ethnically, racially, and eco-
nomically diverse populations.  The study will track sex, age, ethnicity, and racial background of subjects. 

BASILICA prospective investigation 
Page 17 of 39 
2018-03-09 
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, without prohibitively expensive follow-up 
testing. 
During the early clinical development of the BASILICA procedure, 3 clinical patients were treated in one 
week at two centers, which suggests the recruitment objectives will be met. 
 
9.0 SAMPLE COLLECTION, STORAGE AND TRACKING PLAN 
Imaging data (from angiography, CT, and echocardiography) constitute the only specimens to be collected.  
CT examinations performed for clinical evaluation prior to signing informed consent may be used as the 
baseline scan. 
CT and fluoroscopy data will be analyzed at the NHLBI DIR Core Laboratory. These data will be transmitted 
on electronic media such as a DVD via carrier or using secure file transfer mechanisms abiding FISMA, 
HIPAA and local institutional standards (such as SFTP or https://secureemail.nih.gov).  
Imaging data are transmitted to a central facility (NHLBI) using secure HIPAA compliant methods and are 
stored in a secure Picture Archive Computer System (PACS), according to local institutional standards. 
Necropsy specimens will be handled according to local institutional medical standards and will be disposed 
accordingly. 
10.0 
BIOSTATISTICAL AND ANALYTICAL CONSIDERATIONS 
10.1 
Sample Size 
The sample size is not statistically derived.  This is a safety and feasibility study that enables patient access 
to a novel medical procedure, when these patients have no other good medical options to treat sympto-
matic aortic valve failure.  
Up to 60 subjects will be consented until 30 subjects undergo attempted BASILICA TAVR in this protocol.   
10.2 
Study Analysis 
Clinical events are classified by the local site Principal Investigator and confirmed by the NIH Principal Inves-
tigator.   The results of the study will be released within 12 months of study completion. 
Primary and secondary analyses will be stratified according to the setting for TAVR, whether native or bio-
prosthetic, and whether the bioprosthetic valve will intentionally be over-expanded to achieve a greater 
than nominal orifice area. 
The study will be analyzed using descriptive statistics, including a case-by-case narrative summary of major 
adverse events.  Kaplan-Meier estimates will be used to estimate the overall survival and the event-free 
survival Afterwards, we will survey for parameters associated with an increased risk of major adverse 
events by exploratory subgroup analysis and regression models. 
10.2.1 Primary efficacy endpoint 
The primary endpoint is Clinical success (measured at exit from the catheterization laboratory).  All of the 
following must be present: 

BASILICA prospective investigation 
Page 18 of 39 
2018-03-09 
- 
Successful BASILICA traversal and laceration of the intended aortic leaflet; and 
- 
Absence of procedural mortality; and 
- 
Successful access, delivery, and retrieval of the BASILICA device system; and 
- 
Successful TAVR device implantation; and 
- 
Absence of acute life-threatening ostial coronary artery obstruction (by immediate hemodynamics, 
by angiography, and by iFR <0.89 if obtained) 
- 
Freedom from emergency cardiac surgery or reintervention related to the BASILICA TAVR proce-
dure, including attempted implantation of coronary artery stents to treat TAVR-induced coronary 
artery obstruction.   
Additional details about primary endpoint 
Valve post-dilatation is not considered unplanned re-intervention.  When pre-positioned coronary artery 
stents are not able to be retrieved, they may be implanted without impacting the primary endpoint.  
10.2.2 Primary safety endpoint 
The primary safety endpoint is freedom from major adverse clinical events (MACE) according to VARC-2 at 
30days. 
10.2.3 Secondary Endpoints 
Secondary endpoints include  
- 
Technical success, defined as clinical success irrespective of coronary artery stenting  
- 
Clinical success without stroke, as determined by site physicians 
- 
Technical success of BASILICA only (delivery and removal of BASILICA catheter equipment, tra-
versal, and laceration of intended aortic leaflet) 
- 
Coronary artery obstruction measured as instantaneous wave-free pressure ratio (iFR) or related 
measurements using a solid-state pressure-transducer guidewire, if measured 
- 
Survival to discharge, to 30d, and to 12mo 
- 
Neurological events as reported by the site clinicians 
- 
Access and vascular complications 
- 
Peri-procedural and spontaneous acute myocardial infarction 
- 
Pericardial effusion or tamponade 
- 
VARC-2 bleeding complications 
- 
AKIN acute kidney injury 
- 
Freedom from hemolytic anemia related to BASILICA TAVR 
- 
BASILICA Device or Procedure related technical failure: acute embolism, mitral valve injury, tra-
versal into left atrium, coronary artery injury induced by BASILICA, etc. 
- 
Rotational orientation of transcatheter heart valve commissures with regard to coronary artery os-
tia 

BASILICA prospective investigation 
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2018-03-09 
- 
Hemodynamic instability caused by BASILICA before TAVR 
- 
TAVR thrombosis on CT or echocardiography during follow-up 
- 
Endocarditis during follow-up 
- 
Outcomes for laceration of native versus surgical aortic valves, for single versus double scallop lac-
eration, and for procedures with versus without bioprosthesis intentional overexpansion 
 
10.2.4 Rationale for primary endpoint 
The main clinical objective of BASILICA is to allow TAVR without causing death from acute coronary artery 
obstruction in patients identified at baseline because of existing valve design and geometry.  The primary 
endpoint is selected to provide a binary summary assessment of procedure success to help assess the clini-
cal utility of the investigational procedure. 
10.2.5 Independent Clinical Events Adjudication 
An independent Clinical Events Adjudication Committee will review all of the following that occur in the 
first year: 
- 
Deaths 
- 
Primary endpoints 
- 
Site-reported strokes 
The CEAC will classify relatedness of the above events to the BASILICA procedure. The PI and the CEAC will agree on a 
charter, but only after the CEAC contract is awarded.  CEAC adjudication prevails over PI classifications. 
10.3 
Stopping Rules and Data Safety Monitoring 
A 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. All members of the 
DSMB are unaffiliated to the study. 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. The DSMB may recom-
mend early termination of the study for considerations of safety and efficacy. Unanticipated Adverse De-
vice Effects (UADEs) will be submitted to the DSMB following the same timelines as the IRB (See section 
9.2.4). 
In the case of death or serious UADE, if the sponsor and the principal investigator 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. 
Each institutional IRB will review all Serious Adverse Events, Unanticipated Adverse Device Effects, and Un-
anticipated Problems, and may choose to suspend or terminate the protocol based on those findings. We 
believe this will protect subject safety.   
We propose different stopping rules based on whether the operator elects intentionally to over-expand the 
bioprosthesis. 

BASILICA prospective investigation 
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2018-03-09 
10.3.1 Anticipated mortality 
There are few data available to guide mortality assumptions. In an international registry of valve-in-valve 
TAVR, the short-term (30-day) mortality of coronary obstruction complicating TAVR was 50%, despite coro-
nary stenting {Ribeiro, 2017 #362183}. The long-term mortality is expected to be larger. There is no registry 
of subjects not offered valve-in-valve TAVR because of threatened coronary obstruction. 
Absent data, we are forced to use judgement and experience to estimate clinically acceptable mortality for 
this group of patients with “no good options.”  We assume that intentional fracture of surgical biopros-
thetic valve frames would confer incremental mortality, although there are no available data. To come to 
this determination, we polled our lead site investigators, who are selected for their high-volume experience 
and quality.  The best estimate of clinically-acceptable 30-day mortality was 15% for standalone BASILICA 
and 20% for BASILICA with valve fracture. 
10.3.2 Stopping Rules for no intentional overexpansion of bioprosthesis stratum 
The study will be monitored to ensure that the mortality within 30-days after the procedure does not sub-
stantially exceed an anticipated rate. We anticipate the rate of 30-day mortality is 15% or less and determine 
the stopping rule by a Bayesian approach [8]. The stopping boundary is reached if the posterior probability 
that the 30-day mortality rate exceeds 15% 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 = 0.9, b =5.1. 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. 
Number of subjects in the stratum 
Stop if the number of deaths within 30 days reaches 
2 
2 
3-6 
3 
7-11 
4 
12-16 
5 
17-21 
6 
22-26 
7 
27-30 
8 
We investigated the performance of the above stopping rule by a simulation study. In each simulation run, 
we generated a study with 30 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 
10% 
15% 
20% 
25% 
30% 
35% 
Proportion of Stopped Studies 
4.8% 
17.3% 
39% 
62.3% 
81.3% 
92.2% 
Average number of subjects 
29.1 
27 
23.5 
19.4 
15.4 
12.1 
Average number of 30-day mortality 
2.9 
4 
4.7 
4.9 
4.6 
4.2 
These simulation results suggest that our stopping rule has a low probability stopping a study when the 
true 30-day mortality rate is 15% or less, and the probability of stopping a study is high when the true 30-

BASILICA prospective investigation 
Page 21 of 39 
2018-03-09 
day mortality rate exceeds 15%.  There, we believe that our Bayesian stopping rule for 30-day mortality has 
satisfactory statistical properties. 
10.3.3 Stopping Rules for intentional overexpansion of bioprosthesis stratum 
The study will be monitored to ensure that the mortality within 30-days after the procedure does not sub-
stantially exceed an anticipated rate. We anticipate the rate of 30-day mortality is 20% or less and determine 
the stopping rule by a Bayesian approach [8]. The stopping boundary is reached if the posterior probability 
that the 30-day mortality rate exceeds 20% 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 data. This 
gives the prior parameters a = 1.2, b =4.8. 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. 
Number of subjects in the ”overexpansion of biopros-
thesis” stratum 
Stop if the number of deaths within 30 days 
reaches 
3-5 
3 
6-8 
4 
9-12 
5 
13-16 
6 
17-20 
7 
21-24 
8 
25-28 
9 
29-30 
10 
We investigated the performance of the above stopping rule by a simulation study. In each simulation run, 
we generated a study with 30 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 
10% 
15% 
20% 
25% 
30% 
35% 
40% 
Proportion of Stopped Studies (%) 
1.6% 
6.9% 
18.9% 
38.3% 
60.5% 
78.5% 
90.5% 
Average number of subjects 
29.6 
28.7 
26.7 
23.6 
19.7 
16 
12.7 
Average number of 30-day mortality 
3 
4.3 
5.3 
5.9 
5.9 
5.6 
5.1 
These simulation results suggest that our stopping rule has a low probability stopping a study when the 
true 30-day mortality rate is 20% or less, and the probability of stopping a study is high when the true 30-
day mortality rate exceeds 20%.  There, we believe that our Bayesian stopping rule for 30-day mortality has 
satisfactory statistical properties. 
10.4 
Off study criteria 
• 
Completion of the 12-month follow-up 
• 
The subject voluntarily withdraws 
• 
Significant subject non-compliance with follow-up visits 
• 
Death 

BASILICA prospective investigation 
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2018-03-09 
11.0 
ADVERSE EVENT REPORTING 
11.1 
Definitions 
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 sub-
ject’s participation in the research, whether or not considered related to the subject’s participation in the 
research. 
 
This will include: 
• 
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 cardiac catheterization procedure and recovery from the 
procedure and do not directly result from use of the investigational device. 
Serious Adverse Event (SAE):  A serious adverse event that results in any of the following and NOT directly 
related to the device.  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. 
Adverse Device Effect (ADE): Any untoward or unintended response to a medical device.  This definition in-
cludes any event resulting from insufficiencies or inadequacies in the instructions for use or the deploy-
ment of the device or any event that is a result of user error. 
During this clinical investigation, an event should be considered related to the device when it is the result 
of: 
• 
BASILICA procedure 
• 
Asahi-Intecc Astato XS 20 guidewire 
An event will be considered NOT related to the BASILICA procedure when it is the result of:  
• 
A pre-existing medical condition 
• 
Clearly attributable to TAVR but not BASILICA part of procedure (example: apical left ventricular 
perforation) 
Anticipated Adverse Device Effects (ADEs): An ADE is an adverse event with a reasonable possibility that the 
device or procedure caused or contributed to the event. The following ADEs are considered anticipated 
based on previous human experience: 
• 
BASILICA device procedure failure including failure to traverse, to lacerate, or to position catheters 
or guidewires  
• 
BASILICA device mechanical failure including wire fracture, including causing embolization requiring 
retrieval 

BASILICA prospective investigation 
Page 23 of 39 
2018-03-09 
• 
Embolization of air, valve debris, atheroma, or thrombus to coronaries, brain, limbs, or viscera 
causing myocardial infarction, stroke, or limb ischemia 
• 
Mitral valve injury such as chordal disruption causing deterioration in mitral valve function 
• 
Hemodynamic instability during BASILICA caused by traction on the aortic valve leaflets, or after 
BASILICA caused by acute or acute-on-chronic aortic valve regurgitation 
• 
Electrical coupling of traversal or laceration system and other conductive structures such as THV 
guidewire 
• 
Other mechanical device failure 
• 
Allergic reaction to anesthesia, contrast media, or device materials 
• 
Valve malposition, reposition, dislocation, migration, or embolization or deployment in unintended 
location 
• 
Prosthetic valve dysfunction, including stenosis, regurgitation and patient-prosthesis mismatch, 
causing symptoms or requiring unplanned re-intervention 
• 
Transcameral shunt, for example, from aorta to left atrium 
• 
Coronary artery injury 
• 
Atrial-ventricular conduction defects to include bundle branch block and complete heart block re-
quiring placement of a temporary or permanent pacemaker 
• 
Cardiac arrhythmia including ventricular fibrillation  
• 
Transient myocardial dysfunction attributed to rapid ventricular pacing required for aortic valve 
implantation, including brady-asystole or pulseless electrical activity, or requiring cardiopulmonary 
resuscitation 
• 
Angina and myocardial ischemia or myocardial infarction 
• 
Coronary artery obstruction or injury that may require intervention, which may represent a failure 
of BASILICA 
• 
Congestive heart failure, elevated natriuretic peptides, or cardiogenic shock that may require inter-
vention 
• 
Infective endocarditis or other infective complications of TAVR 
• 
Infection or sepsis including access sites, lung, urinary tract, or other system infection related to 
procedure or its complications 
• 
Left ventricular, ventricular septal, or left atrial perforation or pseudoaneurysm 
• 
Pericardial effusion or tamponade 
• 
Hypertension 
• 
Hypotension requiring fluid resuscitation, vasopressor support or mechanical circulatory support or 
chest compressions 
• 
Stroke, transient ischemic attacks, or seizure 
• 
Hemolysis (defined as anemia requiring transfusion with significant or dramatic schizocytes on pe-
ripheral blood examination and depressed haptoglobin)  
• 
Low platelets or thrombocytopenia 
• 
Mechanical injury to the myocardium, access vasculature, cardiac valves that may require interven-
tion 
• 
Bleeding leading to anemia and blood transfusions 
• 
Aortic valve thrombosis 
• 
Retroperitoneal bleed, hematoma, fistula, or other access site injury 
• 
Contrast-induced nephropathy requiring temporary or permanent hemodialysis or medical treat-
ment 
• 
Volume overload, pleural effusion, or dyspnea from procedure-related volume perturbations  
• 
Respiratory insufficiency failure requiring oxygen therapy, mechanical support or mechanical venti-
lation 

BASILICA prospective investigation 
Page 24 of 39 
2018-03-09 
• 
Pain including back pain, access site pain, and generalized pain 
• 
Mechanical circulatory support including emergency cardiopulmonary bypass 
• 
Emergency cardiac surgery 
• 
Cardiac arrest 
• 
Death 
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.  
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 (21 CFR 812.3(s)). 
Unanticipated Problem (UP): An unanticipated problem is any incident, experience, or outcome that meets 
ALL of the following criteria: 
• 
Unexpected in terms of nature, severity, or frequency in relation to: 
a. the research risks that are described in the IRB-approved research protocol and informed consent docu-
ment, Investigator’s Brochure or other study documents, and  
b. the characteristics of the subject population being studied, and  
• 
Related or possibly related to participation in the research, and  
• 
Places subjects or others at a greater risk of harm (including physical, psychological, economic, or 
social harm) than was previously known or recognized.  
Protocol Deviation: A protocol deviation is any change, divergence, or departure from the study design or 
procedures of an IRB-approved research protocol. 
Non-Compliance 
Non-compliance is defined as failure to comply with applicable NIH Human Research Protections Program 
(HRPP) policies, IRB requirements, or regulatory requirements for the protection of human research sub-
jects. 
Non-compliance may be further characterized as: 
1. Serious non-compliance: Non-compliance that: 
a. Increases risks, or causes harm, to participants. 
b. Decreases potential benefits to participants. 
c. Compromises the integrity of the NIH HRPP. 
d. Invalidates the study data. 
2. Continuing non-compliance: Non-compliance that is recurring. 
3. Minor (non-serious) non-compliance: Non-compliance that is neither serious nor continuing. 
 

BASILICA prospective investigation 
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2018-03-09 
11.2 
Adverse event management: 
The following adverse event management guidelines are intended to ensure the safety of each subject 
while on the study.  Adverse events and adverse device effects will be attributed to study procedure and 
graded by severity according to the following tables: 
11.2.1 Grading of adverse events and adverse device effects 
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 inter-
vention. 
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 re-
quires medical intervention and prolonged hospitalization.  
 
11.2.2 Attribution of adverse events to the research protocol 
The relatedness of adverse events will be classified as: 
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 alter-
native causes, such as underlying disease, concomitant medications, or con-
comitant 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 at-
tribution of the event to the device or procedure cannot be excluded. How-
ever, alternative causes—such as underlying disease, concomitant medica-
tions, or concomitant treatments—are presumably responsible. 
Unlikely 
It is doubtful the event is related to the research protocol. The event can rea-
sonably be explained by other factures, including underlying disease, concomi-
tant 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.  
 
 

BASILICA prospective investigation 
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2018-03-09 
11.2.3 Adverse Event Reporting 
Adverse event recording will start on Day (0) of the BASILICA TAVR procedure and will continue through the 
12 month Follow Up. New events or conditions present at baseline that increase in severity will be rec-
orded and evaluated and reported on the case report form. Once the subject has completed the 30 day 
follow up, only serious adverse events (SAE), serious adverse device effects (SADE), unanticipated device 
effects (UADE) and unanticipated problems (UP) will be reported to the Sponsor.  It is the responsibility of 
the site investigator to report adverse events and adverse device effects to their respective IRBs or other 
regulatory bodies according to their reporting requirements. Monitoring visits will be conducted by the 
Sponsor to review source documentation, and accuracy and completion of the adverse event case report 
forms. 
11.2.4 Adverse event reporting timeframes: 
Serious Adverse Events (SAEs) 
• 
All serious adverse events will be reported to the Sponsor immediately but not later than 3 
working days from the event. The respective institutional IRB should be notified according to 
their requirements.  
• 
The serious adverse event will be evaluated by the sponsor. If determined to be an unantici-
pated adverse device effect that increases the risk to the participating subjects, the sponsor 
will terminate the investigation within 5 days after making the determination, and not later 
than 15 working days after the sponsor was first notified of the event. [21 CFR 812.46] 
Unanticipated Adverse Device Effects (UADE) 
• 
Must be reported to the Sponsor and the institutional IRB immediately but no later than 10 
working days after the investigator learns of the event. [21 CFR 812.150] 
• 
Unanticipated Adverse Device Effects should be reported via telephone as well as on the ad-
verse event section of the case report form.  
• 
If the event is determined by the Sponsor to be a UADE, the Sponsor will report the event to all 
investigators to enable reporting to their respective IRB/regulatory bodies. The Sponsor will 
provide this notification to participating sites and to the FDA within 10 working days after they 
first receive notice of the effect.  [21 CFR 812.150] 
• 
All Unanticipated Adverse Device Effects will be reported by the Sponsor to the NHLBI IRB im-
mediately upon notification but no later than 10 working days.  
Deaths 
• 
The investigator will notify the Sponsor immediately but within 3 working days of notification 
of a subject’s death, whether the death is device related or clinical condition. Institutional IRB’s 
will be notified according to the specific institutional regulatory requirements for reporting a 
death.  
• 
The Sponsor will notify the NHLBI IRB of a subject’s death within 7 days.  
• 
A subject’s death will be recorded on the Case Report Form.  

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2018-03-09 
12.0 
HUMAN SUBJECT PROTECTION 
12.1 
Rationale for Subject Selection 
12.1.1 Study population: 
Subjects are selected for being adults who are determined otherwise likely to benefit from transcatheter 
aortic valve replacement yet are expected to suffer TAVR-related left coronary artery obstruction. The de-
termination will be made by the local institutional multidisciplinary heart team.   No patient will be ex-
cluded from participation based on gender, race or ethnicity.   
Subjects who are unable to provide consent may be enrolled, if allowed by participating IRBs. 
12.2 
Risks and Discomforts 
A formal risk analysis is provided in APPENDIX A. 
Risks of TAVR will be considered separately from the risks of preparatory BASILICA before TAVR.  Known 
risks of TAVR, which is a clinical procedure using approved medical devices as intended, include: 
• 
Death  
• 
Stroke/transient ischemic attack, clusters or neurological deficit  
• 
Paralysis  
• 
Permanent disability  
• 
Respiratory insufficiency or respiratory failure  
• 
Hemorrhage requiring transfusion or intervention  
• 
Cardiovascular injury including perforation or dissection of vessels, ventricle, myocardium or 
valvular structures that may require intervention  
• 
Pericardial effusion or cardiac tamponade  
• 
Embolization including air, calcific valve material or thrombus  
• 
Infection including septicemia and endocarditis  
• 
Heart failure  
• 
Myocardial infarction  
• 
Renal insufficiency or renal failure  
• 
Conduction system defect which may require a permanent pacemaker  
• 
Arrhythmia  
• 
Retroperitoneal bleed  
• 
AV fistula or pseudoaneurysm  
• 
Reoperation  
• 
Ischemia or nerve injury  
• 
Restenosis  
• 
Pulmonary edema  
• 
Pleural effusion  
• 
Bleeding  
• 
Anemia  
• 
Abnormal lab values (including electrolyte imbalance)  
• 
Hypertension or hypotension  
• 
Allergic reaction to anesthesia, contrast media, or device materials  
• 
Hematoma  
• 
Syncope  

BASILICA prospective investigation 
Page 28 of 39 
2018-03-09 
• 
Pain or changes at the access site  
• 
Exercise intolerance or weakness  
• 
Inflammation  
• 
Angina  
• 
Heart murmur  
• 
Fever  
• 
Cardiac arrest  
• 
Cardiogenic shock  
• 
Emergency cardiac surgery  
• 
Cardiac failure or low cardiac output  
• 
Coronary flow obstruction/transvalvular flow disturbance  
• 
Device thrombosis requiring intervention  
• 
Valve thrombosis  
• 
Device embolization  
• 
Device migration or malposition requiring intervention  
• 
Valve deployment in unintended location  
• 
Valve stenosis  
• 
Structural valve deterioration (wear, fracture, calcification, leaflet tear/tearing from the stent 
posts, leaflet retraction, suture line disruption of components of a prosthetic valve, thickening, 
stenosis)  
• 
Device degeneration  
• 
Paravalvular or transvalvular leak  
• 
Valve regurgitation  
• 
Hemolysis  
• 
Device explants  
• 
Nonstructural dysfunction  
• 
Mechanical failure of delivery system, and/or accessories  
• 
Rotational mal-orientation of Sapien 3 THV such that commissural post obstructs coronary os-
tium despite successful BASILICA 
 
Anticipated risks of preparatory BASILICA before TAVR include: 
• 
Death 
• 
Embolization of air, valve debris, atheroma, or thrombus to coronaries, brain, limbs, or viscera 
causing myocardial infarction, stroke, or limb ischemia 
• 
Severe aortic regurgitation after laceration before TAVI, causing hypotension or cardiogenic 
shock including requiring cardiopulmonary resuscitation, chest compressions, vasoactive medi-
cations, and/or mechanical circulatory support 
• 
Avulsion or other injury of the native or prosthetic aortic valve leaflet 
• 
Inadvertent injury of the mitral valve apparatus 
• 
Traversal into the left atrium or other non-target chamber 
• 
Pericardial effusion or tamponade requiring drainage 
• 
Electrical coupling of traversal guidewire and bioprosthetic valve frame 
• 
Native coronary artery ostial injury from electrosurgery or BASILICA guide catheter mechanical 
disruption 
• 
Vascular access site injury 
• 
Hemolysis related to blood flow around the lacerated aortic leaflets 
• 
Acute kidney injury related to BASILICA and to follow-up CT examination 

BASILICA prospective investigation 
Page 29 of 39 
2018-03-09 
 
The sponsor and investigators recognize these risks are high and reflect the underlying comorbidities, yet 
consider procedural hemorrhage overall to be an acceptable compromise to enable treatment of the un-
derlying mitral valve failure in patients otherwise ineligible. 
12.2.1 Risks Related to Radiation 
In this research protocol, subjects will be exposed to radiation from 2 CT scans.  The CT scans are per-
formed for research surveillance of transcatheter heart valve dysfunction.  It is estimated that the amount 
of research radiation that a subject will be exposed to during participation in this research protocol will be 
approximately 3-4 REM from the CT scans, and 72mSv[9] from approximately 60-100 minutes of research 
fluoroscopy during performance of BASILICA and TAVR.  This is equivalent to 740 chest X-rays. We be-
lieve the total fluoroscopy exposure to be justifiable in this setting, given the seriousness of their cardiovas-
cular disease and limited options. We estimate the benefit to the research subjects for these procedures to 
outweigh the risks.  
12.2.2 Data collection from patients who have undergone BASILICA at participating sites 
before this protocol begins enrollment 
As of the time of submission of this protocol for review, 3 patients are known to have undergone 
standalone TAVR with BASILICA.  We wish to aggregate all available follow-up data on these patients to the 
extent possible, including patients who have died during the follow-up period. This number of patients ana-
lyzed retrospectively will not count against (“reduce”) the number of prospectively enrolled patients. 
Subjects must have undergone BASILICA TAVR before enrollment begins in this protocol, which is expected 
October 2017.  Retrospective findings will be analyzed separately from the subjects in the main (prospec-
tive) investigational IDE arm. 
12.2.3 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 and de-identified for transmission to participating subcontracting investigators, such as 
core imaging laboratories, clinical events adjudication committee, and statistician. 
DICOM data will be stored in a secured NIH research PACS system for analysis, including personally identifi-
able information.  
13.0 
TEST ARTICLE 
13.1 
Asahi-Intecc Astato XS 20, 510(k) K103057 
13.1.1 Indications For Use 
The Astato 0.014” guidewire is used for transcatheter electrosurgery in two steps in this procedure.  First it 
is used for leaflet traversal during electrification.  This procedure is similar to the use of the Astato XS20 
and an amputated Asahi Confienza Pro 12 in the transcaval IDE investigation recently published [10]. 
Second, the midshaft is focally denuded and electrified for the leaflet traversal step.  This is described in 
the pre-clinical [5] and early clinical [6] LAMPOON manuscripts. 
Neither of these procedures are addressed in the indications for use: 

BASILICA prospective investigation 
Page 30 of 39 
2018-03-09 
Asahi-Intec Astato XS 20: This product is intended to facilitate the placement and exchange of diagnos-
tic and therapeutic devices during intravascular procedures. This device is intended for peripheral vas-
cular use only. 
13.1.2 In vitro testing of bedside modification 
We performed a benchtop investigation of the tensile strength implications of intended (“conventional”) 
and unintended (“undesirable”) bedside modification of the Astato guidewire shaft.   Using the available 
testing equipment, the BASILICA modification of the Astato guidewire left a fracture force exceeding 75N in 
all tests, compared with the ISO 11070-2014, part 8.6 limit (which is 5N) by over tenfold.  See Appendix B. 
We believe this demonstrates the safety of the guidewire modification when following the prescribed tech-
nique. 
14.0 
INVESTIGATOR ADMINISTRATIVE REQUIREMENTS 
14.1 
Good Clinical Practice 
The study will be conducted in accordance with the International Conference on Harmonisation (ICH) E6 
(Guideline for Good Clinical Practice), Title 21 of the Code of Federal Regulations, Parts 50 (Protection of 
Human Subjects), and 56 (Institutional Review Boards), and other appropriate regulatory requirement(s). 
The Investigator will be thoroughly familiar with the BASILICA TAVR technique as described in the protocol 
and the Investigational plan. Essential clinical documents will be maintained to demonstrate the validity of 
the study and the integrity of the data collected. Regulatory files should be established at the beginning of 
the study, maintained for the duration of the study and retained according to the appropriate regulations. 
14.2 
IRB Submissions 
The IRB/IEC and other appropriate institutional regulatory bodies will review all appropriate study docu-
mentation in order to safeguard the rights, safety, and well-being of the subjects. The study will only be 
conducted at sites where IRB/IEC and other appropriate institutional regulatory body approval have been 
obtained. The protocol, informed consent, safety updates, annual progress reports, and any revisions to 
these documents will be provided to the IRB/IEC and other appropriate institutional regulatory bodies by 
the Investigator. 
14.3 
Subject Information and Informed Consent 
After the study has been fully explained, written informed consent will be obtained from the subject or 
his/her legal representative prior to study participation. The method of obtaining and documenting the in-
formed consent and the contents of the consent will comply with ICH-GCP and all applicable regulatory re-
quirement(s). 
Subjects who are unable to provide consent may be enrolled, if allowed by participating IRBs.  Consent for 
these subjects must be obtained from a legally authorized representative. The process for obtaining this 
consent must conform to local human subjects protection policies and to state laws. 
Waiver of consent is requested to collect de-identified clinical data into a retrospective registry arm of pa-
tients treated before IDE enrollment begins nationwide, on the grounds that the retrospective collection of 
de-identified clinical data imparts no increase over minimal risk and that informed consent is impractical in 
this population of extremely ill and elderly patients, many of whom have poor survival despite TAVI, and 
many of whom have severe disability. 

BASILICA prospective investigation 
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2018-03-09 
14.4 
Subject Confidentiality 
In order to maintain subject privacy, all CRFs, accountability records, study reports, and communications 
will identify the subject by initials and the assigned subject number. The Investigator will grant monitor(s) 
and auditor(s) from the Sponsor or its designee and regulatory authority (ies) access to the subject’s origi-
nal 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 per-
mitted by the applicable laws and regulations. 
14.5 
Protocol Compliance 
The Investigator will conduct the study in compliance with the protocol provided by the Sponsor, and given 
approval/favorable opinion by the IRB/IEC and other appropriate institutional regulatory bodies. Modifica-
tions to the protocol should not be made without agreement of both the Investigator and the Sponsor. 
Changes to the protocol will require written IRB/IEC and other appropriate institutional regulatory body 
approval/favorable opinion prior to implementation, except when the modification is needed to eliminate 
an immediate hazard(s) to subjects. The IRB/IEC may provide, if applicable regulatory authority (ies) permit, 
expedited review and approval/favorable opinion for minor change(s) in ongoing studies that have the ap-
proval /favorable opinion of the IRB/IEC and other appropriate institutional regulatory bodies. The Sponsor 
will submit all protocol modifications to the regulatory authority(ies) in accordance with the governing reg-
ulations. 
When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to subjects, 
the Investigator will contact the Sponsor, if circumstances permit, to discuss the planned course of action. 
Any departures from the protocol must be fully documented in the CRF and source documentation. 
14.6 
Direct Access to Source Data 
Monitoring and auditing procedures developed by the Sponsor will be followed, in order to comply with 
GCP guidelines. 
Regulatory authorities, the IRB/IEC and other appropriate institutional regulatory bodies, and/or the Spon-
sor 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 Investigator, who must provide 
support at all times for these activities. 
14.7 
Case Report Form Completion 
CRFs will be completed for each study subject. It is the Principal Investigator’s responsibility to ensure the 
accuracy, completeness, and timeliness of the data reported in the subject’s CRF. Source documentation 
supporting the CRF data should indicate the subject’s participation in the study and should document the 
dates and details of study procedures, AEs, and subject status. 
The Principal Investigator or designated representative, should complete the CRF screens as soon as possi-
ble after information is collected, preferably on the same day that a study subject is seen for an examina-
tion, treatment, or any other study procedure but no more than 5 days post procedure. An explanation 
should be given for all missing data. 
The Principal Investigator must sign and date the Investigator’s Statement at the end of the CRF to endorse 
the recorded data. 

BASILICA prospective investigation 
Page 32 of 39 
2018-03-09 
14.8 
Record Retention 
The Investigator will maintain all study records according to ICH-GCP and applicable regulatory require-
ment(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 ap-
plicable regulatory requirement(s). If the 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. 
The Sponsor has full rights over any invention, discovery, or innovation, patentable or not, that may occur 
when performing the study. 
14.9 
Publication and Presentation of Study Findings and Use of Information 
It is anticipated that the results of this study will be presented at scientific meetings and/or published in a 
peer reviewed scientific or medical journal. A Publications Committee comprised of Investigators participat-
ing in the study and representatives from the Sponsor, as appropriate, will be formed to oversee the publi-
cation and presentation of the study results, which will reflect the experience of all participating clinical 
sites. No publication or disclosure of study results will be permitted except under the terms and conditions 
of a separate written agreement between Sponsor and the investigator and/or the investigator's institu-
tion. 
14.10 Study Eligibility Committee 
Clinical data for all research candidates are confirmed by the study eligibility committee before enroll-
ment. 
The study eligibility committee consists of the NHLBI investigators and the local site principal investiga-
tors.  A quorum of the committee requires a local site investigator where the candidate is not to be en-
rolled, as well as at least two NHLBI investigators. 
 
15.0 
SPONSOR REGULATORY REQUIREMENTS 
15.1 
Role of Sponsor 
As the study sponsor of this clinical study, Dr. Robert Lederman has the overall responsibility for the con-
duct of the study, including assurance that the study meets the regulatory requirements of the appropriate 
regulatory bodies.  
15.2 
General Duties 
The Sponsor's general duties consist of submitting the appropriate regulatory applications, selecting inves-
tigators, obtaining their signed agreement, providing them with the information necessary to conduct the 
study, ensuring proper clinical site monitoring, and ensuring study subject informed consent is obtained.   
15.3 
Monitoring 
The study will be monitored by the Sponsor designee, an independent contract research organization. 
Monitoring will be done by personal visits and will include on-site review of the informed consent docu-
ments and case report forms for completeness and clarity, cross-checking with source documents, and clar-
ification of administrative matters will be performed. The review of medical records will be performed in a 

BASILICA prospective investigation 
Page 33 of 39 
2018-03-09 
manner to ensure that subject confidentiality is maintained. The site monitor will ensure that the investiga-
tion is conducted according to protocol design and regulatory requirements by frequent communications 
(letter, e-mail, telephone, and fax). 
15.4 
Site Selection and Training 
The sponsor or its designee (national co-principal investigator) will ensure appropriate training in the tech-
nique of caval-aortic access prior to enrollment at any participating institution. 
15.4.1 Site selection: 
Site selection will be based on  
1. Physician expression of interest and need to apply this treatment approach to patients at the site. 
2. Physician prior experience performing or proctoring 10 transcaval TAVR procedures to assure com-
petence in transcatheter electrosurgery.  Preference given to sites with prior experience with LAM-
POON TMVR experience. 
3. Site prior participation in IDE protocols evaluating a treatment of structural heart disease 
4. Site ability to obtain CT examinations that are satisfactory for consideration of BASILICA TAVR. 
5. Site investigators willing and able to comply with the requirements of this protocol. 
A waiver for criterion 2 is specifically applied to Site #1, which was the first to perform BASILICA TAVR in 
patients. To compensate for limited transcaval experience, every research BASILICA procedure will be proc-
tored by experienced transcaval operators until the criterion is met. 
15.4.2 Site training: 
Site training will consist of 
• 
Principal investigator and/or sponsor didactic training about the technique, preclinical, and clinical 
experience to date. 
• 
Proctored conduct of BASILICA TAVR procedures in patients at the local site, at the sole discretion 
of the Sponsor and/or Principal Investigator.   
• 
Completion of training, and suitability for independent BASILICA TAVR enrollment, will be certified 
by the Principal Investigator and with the concurrence of the Sponsor.  
 

BASILICA prospective investigation 
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2018-03-09 
REFERENCES 
1. 
Dvir D, Webb JG, Bleiziffer S, Pasic M, Waksman R, Kodali S, Barbanti M, Latib A, Schaefer U, Rodes-
Cabau J, Treede H, Piazza N, Hildick-Smith D, Himbert D, Walther T, Hengstenberg C, Nissen H, 
Bekeredjian R, Presbitero P, Ferrari E, Segev A, de Weger A, Windecker S, Moat NE, Napodano M, 
Wilbring M, Cerillo AG, Brecker S, Tchetche D, Lefevre T, De Marco F, Fiorina C, Petronio AS, Teles 
RC, Testa L, Laborde JC, Leon MB, Kornowski R, Valve-in-Valve International Data Registry I, 
Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA, 
2014;312(2):162. [25005653] 
2. 
Webb JG, Mack MJ, White JM, Dvir D, Blanke P, Herrmann HC, Leipsic J, Kodali SK, Makkar R, Miller 
DC, Pibarot P, Pichard A, Satler LF, Svensson L, Alu MC, Suri RM, Leon MB, Transcatheter Aortic 
Valve Implantation Within Degenerated Aortic Surgical Bioprostheses: PARTNER 2 Valve-in-Valve 
Registry. J Am Coll Cardiol, 2017;69(18):2253. [28473128] 
3. 
Ribeiro HB, Rodés-Cabau J, Blanke P, Leipsic J, Park JK, Bapat V, Makkar R, Simonato M, Barbanti M, 
Schofer J, Bleiziffer S, Latib A, Hildick-Smith D, Presbitero P, Windecker S, Napodano M, Cerillo AG, 
Abdel-Wahab M, Tchetche D, Fiorina C, Sinning JM, Cohen MG, Guerrero ME, Whisenant B, 
Nietlispach F, Palma JH, Nombela-Franco L, de Weger A, Kass M, de Brito FS, Lemos PA, Kornowski 
R, Webb J, Dvir D, Incidence, Predictors and Clinical Outcomes of Coronary Obstruction Following 
Transcatheter Aortic Valve Replacement for Degenerative Bioprosthetic Surgical Valves: Insights 
from the VIVID Registry  [In Press]. European heart journal, 2017 
4. 
Simonato M, Webb J, Kornowski R, Vahanian A, Frerker C, Nissen H, Bleiziffer S, Duncan A, Rodes-
Cabau J, Attizzani GF, Horlick E, Latib A, Bekeredjian R, Barbanti M, Lefevre T, Cerillo A, Hernandez 
JM, Bruschi G, Spargias K, Iadanza A, Brecker S, Palma JH, Finkelstein A, Abdel-Wahab M, Lemos P, 
Petronio AS, Champagnac D, Sinning JM, Salizzoni S, Napodano M, Fiorina C, Marzocchi A, Leon M, 
Dvir D, Transcatheter Replacement of Failed Bioprosthetic Valves: Large Multicenter Assessment of 
the Effect of Implantation Depth on Hemodynamics After Aortic Valve-in-Valve. Circ Cardiovasc 
Interv, 2016;9(6). [27301396] 
5. 
Khan JM, Rogers T, Schenke WH, Mazal JR, Faranesh AZ, Greenbaum AB, Babaliaros VC, Chen MY, 
Lederman RJ, Intentional Laceration of the Anterior Mitral Valve Leaflet to Prevent Left Ventricular 
Outflow Tract Obstruction During Transcatheter Mitral Valve Replacement: Pre-Clinical Findings. 
JACC Cardiovasc Interv, 2016;9(17):1835. [27609260] 
6. 
Babaliaros VC, Greenbaum AB, Khan JM, Rogers T, Wang DD, Eng MH, O'Neill WW, Paone G, 
Thourani VH, Lerakis S, Kim DW, Chen MY, Lederman RJ, Intentional Percutaneous Laceration of the 
Anterior Mitral Leaflet to Prevent Outflow Obstruction During Transcatheter Mitral Valve 
Replacement: First-in-Human Experience. JACC Cardiovasc Interv, 2017;10(8):798. [28427597] 
7. 
Dvir D, Leipsic J, Blanke P, Ribeiro HB, Kornowski R, Pichard A, Rodes-Cabau J, Wood DA, Stub D, 
Ben-Dor I, Maluenda G, Makkar RR, Webb JG, Coronary obstruction in transcatheter aortic valve-in-
valve implantation: preprocedural evaluation, device selection, protection, and treatment. Circ 
Cardiovasc Interv, 2015;8(1). [25593122] 
8. 
Geller NL, Follman D, Leifer ES, Carter SL, Design of Early Trials in Stem Cell Transplantation: A 
Hybrid Frequentist-Bayesian Approach in Advances in Clinical Trial Biostatistics, N.L. Geller, Editor 
2003, Chapman & Hall / CRC Press  
9. 
Uniyal SC, Chaturvedi V, Sharma SD, Rawat A, Patient Dosimetry during Interventional Cardiac 
Procedures in a Dedicated Catheterization Laboratory. Radiat Prot Dosimetry, 2016. [27744352] 
10. 
Greenbaum AB, Babaliaros VC, Chen MY, Stine AM, Rogers T, O'Neill WW, Paone G, Thourani VH, 
Muhammad KI, Leonardi RA, Ramee S, Troendle JF, Lederman RJ, Transcaval Access and Closure for 
Transcatheter Aortic Valve Replacement: A Prospective Investigation. J Am Coll Cardiol, 
2017;69(5):511. [27989885] 

BASILICA prospective investigation 
Page 35 of 39 
2018-03-09 
11. 
Fischer R, Factors to Consider When Making Benefit-Risk Determinations in Medical Device 
Premarket Approval and De Novo Classifications, F.a.D.A. Department of Health and Human 
Services, Center for Devices and Radiologic Health, Editor 2012, Food and Drug Administration: 
Silver Spring, Maryland. 
 
 
 

KEY LEVEL 
1 
2 
3 
4 
5 
Probability 
Rare 
Uncommon 
Common 
Normal 
 
Severity 
Easy to correct, no anticipated harm 
to patient 
Difficult to correct, no antici-
pated harm to patient 
Potentially harmful to patient 
Likely harmful, even with im-
mediate correction 
Life threatening 
Risk Score 
1-4 
5-9 
10-20 
>20 
 
Risk Interpretation 
Negligible 
Tolerable  
Tolerable but undesirable 
Intolerable 
 
BASILICA prospective investigation 
Page 36 of 39 
2017-11-13 
APPENDIX A: Risk Analysis 
This is a patient-centered risk analysis[11] in accordance with 21 CFR 812.25(c).  It considers probable and not possible risk.  This risk analysis applies to candi-
dates for TAVR with BASILICA, who have a fatal disease with few or no therapeutic options.  
Category 
Failure 
Impact 
Severity Likelihood / 
frequency 
Score Available evidence to 
consider risk 
Mitigation 
BASILICA 
Insufficiently basal leaflet 
laceration 
Failure to spare 
coronary ostium 
4 
2 
8 
Inadequate leaflet splaying 
causing inadequate coronary 
artery protection from bio-
prosthetic leaflet 
Standard coronary artery protection, 
bailout Impella 
 
Mitral chordal laceration Mitral valve regur-
gitation 
4 
2 
8 
Mitral valve regurgitation 
Snare in LVOT, assess for chordal entrap-
ment by TEE before laceration 
 
Traversal into left atrium 
Puncture of aortic 
sinus or aorto-
mitral curtain 
2 
3 
6 
Guidewire traversal into LA is 
probably clinically inconse-
quential; Requires withdrawal 
and repeat traversal 
Guidewire positioning relative to biopros-
thetic valve frame; CT-derived landmarks; 
Inability to snare if LA position; May require 
repeat traversal; Low energy and short 
burns to minimize collateral RF damage 
 
Rotational mal-orienta-
tion of Sapien 3 THV such 
that commissural post 
obstructs coronary os-
tium despite successful 
BASILICA 
Failure to spare 
coronary ostium 
4 
3 
12 
Coronary obstruction by THV 
commissural posts subverts 
the objective of BASILICA 
which is to prevent coronary 
obstruction 
Attempt rotational alignment with greature 
curvature of S3 THV delivery system; Model 
alignment on 3D-printed aorta; Use con-
comittant standard coronary stent protec-
tion methods 
 
Severe aortic regurgita-
tion after laceration be-
fore TAVI 
Cardiogenic shock 
3 
3 
9 
Hypoperfusion; accelerated 
TAVI implantation 
Preposition TAVI Pigtail or THV; Tachypac-
ing; Mechanical support devices as needed 
 
Electrical coupling of lac-
eration system and THV 
guidewire  
Likely dissipation 
of current. Possi-
ble endocardial in-
jury. 
2 
1 
2 
Failed electrosurgery, or inad-
vertent electrosurgery via 
TAVI guidewire causing LV en-
docardial injury and failed lac-
eration 
THV Pigtail in LV during laceration to avoid 
electrical coupling 

KEY LEVEL 
1 
2 
3 
4 
5 
Probability 
Rare 
Uncommon 
Common 
Normal 
 
Severity 
Easy to correct, no anticipated harm 
to patient 
Difficult to correct, no antici-
pated harm to patient 
Potentially harmful to patient 
Likely harmful, even with im-
mediate correction 
Life threatening 
Risk Score 
1-4 
5-9 
10-20 
>20 
 
Risk Interpretation 
Negligible 
Tolerable  
Tolerable but undesirable 
Intolerable 
 
BASILICA prospective investigation 
Page 37 of 39 
2017-11-13 
Category 
Failure 
Impact 
Severity Likelihood / 
frequency 
Score Available evidence to 
consider risk 
Mitigation 
 
Electrical coupling of tra-
versal guidewire and bio-
prosthetic valve frame 
Likely dissipation 
of current. Possi-
ble endocardial in-
jury. 
2 
1 
2 
Failed electrosurgery, or inad-
vertent heating of surgical bi-
oprosthetic valve frame 
Direct traversal wire away from valve 
frame; Surrounding fibrotic tissue makes 
this interaction unlikely 
 
Native coronary artery 
ostial injury from electro-
surgery or BASILICA guide 
catheter mechanical dis-
ruption 
Left main coronary 
artery disruption 
4 
2 
8 
Require PCI with late sequelae Left main coronary stent using bailout de-
vices already in place 
Electrosur-
gery 
Ventricular fibrillation 
Life-threatening 
but reversible 
4 
1 
4 
VF from electrosurgical stimu-
lation of LVOT after successful 
bioprosthetic leaflet traversal 
Prevent: Short bursts; Survey: Continuous 
ECG monitoring; Treat: Defibrillation and 
antiarrhythmics as needed. 
 
Difficult laceration 
Potential proce-
dure failure 
2 
2 
4 
Procedure failure precluding 
purported benefit of BASILICA 
Focal denudation of guidewire; Focal kink 
of guidewire; Focus charge using Piggyback 
insulation; Focus charge using non-conduc-
tive dextrose injection during electrosur-
gery 
 
Thromboembolism 
Electrosurgery 
may cause intra-
vascular coagula-
tion and char 
2 
1 
2 
Thromboembolism including 
stroke 
Prevent: Anticoagulation; limit electrosur-
gery duration and energy; Consider analogy 
to LV endocardial radiofrequency ablation 
for EP 
Percutane-
ous proce-
dures 
Vascular access site in-
jury 
Additional arterial 
access for BASIL-
ICA (two sheaths) 
2 
3 
6 
Vascular access site injury 
Ipsilateral access for two BASILICA sheaths 
to avert carina injury 

KEY LEVEL 
1 
2 
3 
4 
5 
Probability 
Rare 
Uncommon 
Common 
Normal 
 
Severity 
Easy to correct, no anticipated harm 
to patient 
Difficult to correct, no antici-
pated harm to patient 
Potentially harmful to patient 
Likely harmful, even with im-
mediate correction 
Life threatening 
Risk Score 
1-4 
5-9 
10-20 
>20 
 
Risk Interpretation 
Negligible 
Tolerable  
Tolerable but undesirable 
Intolerable 
 
BASILICA prospective investigation 
Page 38 of 39 
2017-11-13 
Category 
Failure 
Impact 
Severity Likelihood / 
frequency 
Score Available evidence to 
consider risk 
Mitigation 
 
ATN from procedural 
contrast and from fol-
low-up contrast CT 
Temporary or 
permanent he-
modialysis 
3 
2 
6 
Temporary or permanent 
hemodialysis 
Minimize contrast exposure. Request 
low-energy and low-contrast time-re-
solved CT to minimize contrast.  Follow 
operator discretion about timing of 
contrast exposure 
 
 
 
 
 
 
 
 
 
 
 

BASILICA prospective investigation 
Page 39 of 39 
2017-11-13 
 
APPENDIX B: Tensile strength implications of bedside modification of Astato XS 20 guidewire 
See attachment.