Comparison of Anticoagulation With Left Atrial Appendage Closure After AF Ablation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Boston Scientific Corporation

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
               
 
             
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1  of 1 0 2  
 
 
 
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure 
after A F A blati o n  
O P TI O N  
 
C LI NI C A L I N V E S TI G A TI O N P L A N 
B S C Pr oject N u m ber: S 2 2 3 9  
N C T # 9 2 3 2 0 9 5 5  
A p pr o ve d electr o nicall y o n 1 9 -Ja n-2 0 2 2  
 
 
S p o ns ore d B y  
B ost o n Scie ntific C or p orati o n  
G lo bal  C lin ical Tr ials, In terv e ntio n al C ard io lo g y  
3 0 0 B os to n S cien tific Way   
M arlb o ro u g h, M A 0 1 7 5 2 -1 2 3 4 U S A  
B ost o n Scie ntific I nter n ati o nal S A  
Parc Val Sai nt -Q ue nti n,  
Bâti me nt H,  
2 R ue Re né Ca u dr o n,  
7 8 9 6 0 V oisi ns le Bret o n ne u x, Fra nce   
B ost o n Scie ntific ( A ustralia) Pt y Lt d  
P O B o x 3 3 2  
B O T A N Y  
N S W 1 4 5 5 A ustralia  
 
T his pr ot oc ol c o nt ai ns c o nfi de nti al i nf or m ati o n  f or use b y t he I n v esti gat ors a n d t heir 
desi g nate d re prese nt ati ves partici pati n g i n t his cli nical i n vesti gati o n. T he pr ot oc ol  s h o ul d be 
hel d c o nfi de ntial a n d mai ntai ne d i n a sec ure l ocati o n . 
D o n ot c o py or distri b ute wit h o ut writte n per missi o n fr o m B ost o n Scie ntific C or p or ati o n.  
 
 
 
 
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2  of 1 0 2  
  
 
 
C o nt act I nf or m ati o n  
R ole  
C o nt act  
B S C Cli nic al C o nt acts     
Elisa bet h Ga bi n, Se ni or Cli nical Trial Ma na ger  
B ost o n Scie ntific I C  
3 0 0 B ost o n Scie ntific Wa y  
Marl b or o u g h, M A 0 1 7 5 2 U S A  
Tele p h o ne: + 1 5 0 8 -6 8 3 -4 7 5 3  
E mail: Elisa bet h. Ga bi n @ bsci.c o m  
 
A n ne C or naille, Se ni or Cli nical Trial Ma na ger  
B ost o n Scie ntific I nter n ati o nal S A S  
2 R ue Re né Ca u dr o n, Bâti me nt H  
7 8 9 6 0 V oisi ns -le-Bret o n ne u x, Fra nce   
Tele p h o ne :  + 3 3 6 0 8 8 6 3 6 5 9  
E mail: A n ne. C or naille @ bsci.c o m  
 
W hit ne y A n ders o n, Cli nical Trial Ma n a ger  
B ost o n Scie ntific I C  
3 0 0 B ost o n Scie ntific Wa y  
Marl b or o u g h, M A 0 1 7 5 2 U S A  
Tele p h o ne: + 1 5 0 8 6 8 3 4 3 8 8  
E mail: W hit ne y. A n ders o n 1 @ bsci.c o m   
 
St u d y Pri nci p al 
I n vesti g at or 
O ussa ma Waz ni , M D 
Secti o n Hea d, Car di ac El ectr o p h ysi ol o g y a n d Paci n g  
T he Cle vela n d Cli nic  
9 5 0 0 E ucli d A ve n ue  
Cle vela n d, O H 4 4 1 9 5  
Ve n d ors/ L a bs  
A list of ve n d ors/la b o rat ories i n v ol ve d i n t he trial is 
mai ntai ne d b y t he s p o ns or .  
 
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
               
 
             
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3  of 1 0 2  
 
O ri gi n al A p pr o v al : 1 4 Dec 2 0 1 8   
C urre nt Versi o n:  E  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
A  
1 4 D E C 2 0 1 8  
Te m pl ate 9 0 7 0 2 6 3 7 _ Re v/ Ver A J  
N A  
N A  
N A  
B  
0 9 A P R 2 0 1 9  
Te m pl ate 9 0 7 0 2 6 3 7 _ Re v/ Ver A L  
Secti o n 5  
U p d ate d I n dic ati o ns f or Use  
T o cl arif y c urre nt de vice 
i n dic ati o n f or c o u ntries 
w here C E m ar k a p plies  
Secti o n 8  
U p d ate d R oll -i n s u bject i nf o r m ati o n 
T o cl arif y w hic h sites, 
re q uire R oll -i ns, as well as 
t he e x pecte d n u m ber of R oll-
i ns 
Secti o n 9  
U p d ate d I ncl usi o n criteri a  
T o cl arif y deter mi n ati o n of 
s uit a bilit y f or t he defi ne d 
pr ot oc ol p h ar m ac ol o gic 
re gi m e n  
Secti o n 1 1  
U p d ate d d at a c ollecti o n re q uire m e nts  
T o cl arif y w h at is re q uire d t o 
be c ollecte d at e a c h visit  
Secti o n 1 1  
A d de d bli n di n g f or Q u alit y -of -Life  
Q uesti o n n aires a n d str o k e sc ales  
B ase d o n F D A fee d b ac k  
Secti o n 1 1  
A d de d l a n g u a ge ar o u n d w h at s h o ul d 
be d o ne if a s u bject’s NI H S S a n d/ or 
M R S h a ve c h a n ge d a n d/ or if t here is 
s us pici o n of a ne ur ol o gic e v e nt 
B ase d o n F D A fee d b ac k  
Secti o n 1 1  
A d de d l a n g u a ge ar o u n d i nc o m plete 
de vice se al a n d f oll o w -u p i m a gi n g  
B ase d o n F D A fee d b ac k  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4  of 1 0 2  
  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
Secti o n 1 3  
U p d ate d st atistic al l a n g u a ge  
T o c o rrect err o rs, as well as 
cl arif y st u d y a n al yses  
Secti o n 1 7  
U p d ate d l a n g u a ge ar o u n d t he 
O P TI O N D F U  
T o cl arif y rel ati o ns hi p 
bet wee n t he O P TI O N D F U 
a n d t he c o m m erci al D F U f or 
c o u ntries w here t he C E m ar k 
a p plies  
C  
1 5 J a n 2 0 2 0  
Te m pl ate 9 0 7 0 2 6 3 7 _ Re v/ Ver A L  
Secti o n 4  
U p d ate d cli nic al st u d y o ver vie w  
T o acc ur atel y reflect st u d y 
st at uses  
Secti o n 8  
A d de d l a n g u a ge re g ar di n g i m pl a nt of 
r oll-i n s u bjects as o p p ose d t o 
e nr oll m e nt of r oll -i n s u bjects 
T o better ali g n wit h t he 
p ur p ose of g ai ni n g i m pl a nt 
e x perie nce vi a r oll -i n s u bjects 
pri or t o e nr oll m e nt i n t he 
r a n d o mize d c o h ort  
Secti o n 8  
I ncre ase d t he gl o b al n u m ber of sites t o 
1 5 0  
T o i ncre ase t he st u d y 
e nr oll m e nt r ate  
Secti o n 9  
A d diti o n al l a n g u a ge re g ar di n g t he use 
of ot her c ar di ac i m a gi n g m o d alities t o 
deter mi ne e xcl usi o n.  C orrecti o n of 
E xcl usi o n Criteri a # 4 t o a d d “ … a n d 
c ar di o versi o n ”  
T o all o w f or st a n d ar d of c are 
assess m e nts t o be use d f or 
deter mi ni n g s u bject 
eli gi bilit y.  E C # 4 c o rrecte d 
i n secti o n 9. 3 t o m atc h 
e xisti n g pr ot oc ol s y n o psis 
fr o m Re v B. 
Secti o n 1 1  
A d de d a secti o n re g ar di n g R oll -I n 
s u bject wi n d o ws 
T o cl arif y visit ti mi n g f or 
R oll -I n s u bjects 
Secti o n 1 1  
I ncl u de d “ Hi g h-ris k P F O n ot detecte d 
at b aseli ne ” as a re as o n t o n ot pr ocee d 
wit h i m pl a nt.  
T o ali g n wit h T T E e x cl usi o n 
criteri a  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 5  of 1 0 2  
  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
Secti o n 1 1  
A d de d det ail f or r a n d o miz ati o n desi g n 
defi ne d as 1: 1 ( de vice:  c o ntr ol)  
T o pr o vi de cl arit y of desi g n  
Secti o n 1 2  
A d de d t he f oll o wi n g n ote: Cli nic al 
st u d y d at a est a blis hi n g s afet y a n d 
effecti ve ness are b ase d o n 
de m o nstr ati o n of peri -de vice fl o w ≤5 
m m as a m e as ure of a de q u ac y of L A A 
se al. Per t he W A T C H M A N F L X D F U, 
if a de q u ate se al is n ot de m o nstr ate d, 
decisi o n t o disc o nti n ue O A C is at 
p h ysici a n  discreti o n  pr o vi de d t h at a n y 
le a k de m o nstr ate d is ≤ 5 m m. N o n-
a p pr o ve d m e as ures/ pr o ce d u res t o 
i m pr o ve se al (e. g.  ‘ kissi n g’ 
W A T C H M A N, v asc ul ar pl u gs, 
e n d o v asc ul ar c oils, etc.) m ust n ot be 
atte m pte d d uri n g t he c o urse of t his 
st u d y. 
Re atte m pts at cl os ure f or a n y 
le a k size h as n ot bee n pr o ve n 
i n r a n d o mize d cli nic al tri als 
t o be s afe a n d/ or effecti ve. 
Secti o n 1 3  
A d de d t he f ail ure t o disc o nti n ue A A D 
after t he bl a n ki n g peri o d as f ail ure  
T o be c o nsiste nt wit h m e dic al 
liter at ure. 
D  
2 5 Se p 2 0 2 0  
Te m pl ate 9 0 7 0 2 6 3 7 _ Re v/ Ver A M  
Secti o n 4  
U p d ate d cli nic al st u d y o ver vie w  
T o acc ur atel y reflect st u d y 
st at uses  
Secti o n 4  
A d de d n ote t h at ne xt ge ner ati o n 
W A T C H M A N Access S yste ms m a y 
bec o m e a v ail a ble d uri n g e nr oll m e nt 
a n d t he y m a y be c o nsi dere d f or t he 
tri al. 
T o a v oi d a f ut ure pr ot oc ol 
a m e n d m e nt d ue t o  
c o m merci aliz ati o n  of ne xt 
ge ner ati o n W A T C H M A N 
Access S yste ms.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6  of 1 0 2  
  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
Secti o n 8  
U p d ate d m e dic ati o n disc o nti n u ati o n 
re q uire m e nts t o ali g n wit h st u d y visits  
T o a v oi d de vi ati o ns i f a 
m e dic ati o n is st o p pe d wit hi n 
a visit wi n d o w  
Secti o n 1 1  
A d de d a d diti o n al l a n g u a ge all o wi n g 
I C E at i m pl a nt a n d C T f or f oll o w-u p 
i m a gi n g 
B ase d o n Steeri n g C o m mittee 
fee d b ac k t o re d uce 
i nt u b ati o ns d uri n g t he 
C O VI D p a n de mic.  
Secti o n 1 1  
U p d ate d ti mi n g o n b aseli ne T T E fr o m 
6 0 d a ys pri or t o r a n d o miz ati o n t o 1 8 0 
d a ys pri or t o r a n d o miz ati o n  
B ase d o n Steeri n g C o m mittee 
fee d b ac k, t o pr o vi de sites 
m ore fle xi bilit y, a n d re d uce 
t he li k eli h o o d of u n necess ar y 
a d diti o n al pr o ce d ures.  
Secti o n 1 1  
U p d ate d d at a c ollecti o n re q uire m e nts 
a n d sc he d ule  
T o a d d ne w i m a gi n g 
m o d alities, a n d all o w rece nt 
he m o gl o bi n a n d pl atelet 
v al ues wit hi n a s u bject’s 
m e dic al rec or d t o be use d at 
b aseli ne  
Secti o n 1 1  
U p d ate d A F assess m e nt t y pe t o 
i ncl u de l o n g st a n di n g persist e nt 
T o m a k e cle a r t h at all A F 
t y pes are bei n g rec o r de d i n 
t he st u d y 
Secti o n 2 0  
U p d ate d t a ble of A ntici p ate d A d verse 
E ve nts  
T o ali g n wit h I F U  
Secti o n 2 1  
U p d ate d A E rec urre nce re p orti n g 
re q uire m e nts  
T o better cl arif y w he n a n 
e v e nt m eets re p orti n g criteri a  
Secti o n 2 1  
U p d ate d S afet y Defi niti o ns t a ble, 
Rel ati o ns hi p t a ble, a n d I n vesti g at or 
Re p orti n g Re q uire m e nts t a ble  
T o i nc or p or ate ne w 
re g ul ati o ns a n d pr o vi de 
f urt her cl arit y 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 7  of 1 0 2  
  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
E  
1 4 J a n 2 0 2 2  
Te m pl ate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
Secti o n 4  
U p d ate d W A T C H M A N Cli nic al 
St u dies St at us  
T o pr o vi de f urt her 
i nf o r m ati o n as t o w hic h 
st u dies h a ve bee n c o m plete d.  
Secti o n 1 0  
U p d ate d t he De vice Gr o u p 
Cl assific ati o n  
T o pr o vi de f urt her 
i nstr ucti o ns t o sites a b o ut 
s u bject cl assific ati o n st at us 
Secti o n 1 0  
U p d ate d “l ost t o f oll o w u p ” defi niti o n  
T o pr o vi de f urt her cl arit y t o 
t he n u m ber of atte m pts i n 
w hic h t o c o nt a ct p atie nts t h at 
are l ost t o f oll o w u p.  
Secti o n 1 1  
U p d ate d D at a C ollecti o n Sc he d ule  
T o pr o vi de f urt her det ails f or 
t he f oll o w u p visits t h at are 
c o n d ucte d b y p h o ne or office.  
Secti o n 1 1  
U p d ate d F oll o w pr oce d ures  
T o pr o vi de t he o pti o n f or 
office or p h o ne c all visits a n d 
ass oci ate d st u d y pr oce d ures 
t o be d o ne gi ve n t he c urre nt 
e n vir o n m e nt wit h C O VI D -
1 9. A d diti o n all y, t o pr o vi de 
g ui d a nce if o utsi de f acilit y 
st a n d ar d of c a re assess m e nt 
d at a us a ge.  
Secti o n 1 1  
L oc al L a b or at or y  
T o cl arif y l a b certific ati o n 
d oc u m e nt ati o n fili n g 
re q uire m e nts.  
Secti o n 1 2  
U p d ate d Cr oss o ver Gr o u p  
T o cl arif y C R F i nf o r m ati o n 
t o e ntere d i n E D C f or 
p atie nts t h at h a d cr osse d 
o ver.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
             
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8  of 1 0 2  
  
 
 
 
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate n u m ber a n d versi o n  
Pr ot oc ol 
Secti o n  
M o difie d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or M o dific ati o n  
Secti o n 2 1  
U p d ate d S afet y Re p orti n g Secti o n  
T o f urt her cl arif y e v e nt 
re p orti n g re q uire m e nts a n d 
u p d ate d d ue t o re g ul ati o ns 
refere nce d  
 
 
 
Secti o n 2 8  
U p d ate d Refere nces  
T o pr o vi de a d diti o n al 
refere nces t o  t he u p d at es i n 
st at us f or W A T C H M A N 
Cli nic al tri als.  
 
 
 
Secti o n 2 9  
U p d ate d Defi niti o ns  
T o pr o vi de f urt her det ail t o 
t he defi niti o ns  
 
 
 
 
 
 
 
 
 
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 9  of 1 0 2  
  
2.  Pr ot oc ol S y n o psis  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
St u d y 
O bjecti ve(s)  
T he pri mar y o bje cti ve of t his st u d y is t o deter mi ne if left atrial a p pe n da ge 
cl os ure wit h t he W A T C H M A N F L X De vice is a reas o na bl e alter nati ve t o 
oral a ntic oa g ulati o n f oll o wi n g perc uta ne o us cat h eter a blati o n f or hi g h ris k 
patie nts wit h n o n -val v ular atrial fi brillati o n.  
Pl a n ne d 
I n dic ati o n(s) 
f or Use  
T he pla n ne d i n dicati o n f or use wit hi n t he O P TI O N st u d y is as f oll o ws:  
T he W A T C H M A N a n d W A T C H M A N F L X De vice are i n dicate d t o re d uce 
t he ris k of t hr o m b oe m b olis m fr o m t he left atrial a p pe n da ge i n s u bjects wit h 
n o n -val v ular atri al fi brillati o n w h o:  
•  Are at i ncreas e d ris k f or str o ke a n d s yste mic e m b olis m base d o n  
C H A 2D S 2-V A Sc sc ores f oll o wi n g cat heter a bl ati o n of atrial 
fi brillati o n; a n d 
•  A re dee me d t o be s uita bl e f or a ntic o a g ulati o n t hera p y 
 
N ote: I n c o u ntries w h ere C E mar k  a p plies, t he O P TI O N i n dicati o n is wit hi n 
t he C E mar k  a p pr o ve d I n dicati o n f or Use.   
St u d y Desi g n  
T his st u d y is a pr os pecti ve, ra n d o mize d, m ulti -ce nter, gl o bal i n vesti gati o n t o 
deter mi ne if left atrial a p pe n da ge cl os ure wit h t he W A T C H M A N F L X 
De vice is a reas o n a ble alt er nati ve t o or al a ntic oa g ulati o n i n patie nts after A F 
a blati o n.  
Pl a n ne d 
N u m ber of 
S u bjects  
A ma xi m u m of 1 6 0 0 s u bjects will be ra n d o mize d i n t he st u d y. 
N ote t he t ot al n u m ber of e nr olle d p atie nts is ex pecte d t o excee d t he n u m b er 
of r a n d o mize d s u bjects si nce sites wit h o ut W A T C H M A N F L X ex perie n ce are 
re q uire d t o perf or m t w o r oll-i n c ases. A m axi m u m of 26 0 p atie nts will be 
tre ate d i n t he r oll-i n p h ase of t he st u dy, i ncl u di n g a p pr oxi m ately 1 3 0 r oll-i n 
s u bjects i n t he U nite d St ates.  
T he r oll -i n c o h ort will be a n alyze d se p ar ately fr o m t he pri m ary c o h ort of 
r a n d o mize d s u bjects. 
Pl a n ne d 
N u m ber of 
Ce nters  / 
C o u ntries  
U p t o 1 5 0 i n vesti gati o nal ce nters w orl d wi de  
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 0  of 1 0 2  
  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
Pri m ar y 
Effecti v e ness 
E n d p oi nt  
W A T C H M A N t hera p y is n o n -i nferi or f or t he occ urre nce of str o ke (i ncl u di n g 
isc he mic a n d/ or he m orr ha gic), all ca use deat h, a n d s yste mic e m b olis m at 3 6 
m o nt hs.  
Pri m ar y S afet y 
E n d p oi nt  
W A T C H M A N t hera p y is s u peri or f or n o n -pr oce d ural blee di n g t hr o u g h 3 6 
m o nt hs (I S T H maj or blee di n g a n d cli nicall y rel e v a nt n o n -maj or blee di n g)  
Sec o n d ar y 
E n d p oi nt  
W A T C H M A N t hera p y is n o n -i nferi or f or I S T H m aj or blee di n g at 3 6 m o nt hs 
(i ncl u di n g pr oce d ural blee di n g) 
A d diti o n al 
A n al ysis  
T he occ urre n ce of:  
•  Str o ke  
•  Is c he mic str o ke 
•  He m orr ha gi c str o ke  
•  Disa bli n g str o ke  
•  N o n -disa bli n g str o ke  
•  S yste mic e m b olis m  
•  Pr oce d ural a n d n o n -pr oce d ural blee di n g  
•  All -ca use d eat h  
•  Car di o vasc ular/ u n k n o w n deat h  
•  N o n -car di o vasc ular deat h  
•  De vice relate d T hr o m b us  
•  De vice Seal  
•  Si n gle pr oce d ure free d o m fr o m A F  
•  Healt hcare res o urce utilizati o n  
•  Q ualit y of life  
Met h o d of 
Assi g ni n g 
Patie nts t o 
Treat me nt  
A s u bject w h o si g ns i nf or me d c o nse nt is c o nsi dere d e nr olle d i n t he st u d y.  
S u bjects will be ra n d o mize d t o O A C or W A T C H M A N F L X i n e q ual 
fas hi o n.  Ra n d o mizati o n will be stratifie d b y se q u e ntial vs. c o nc o mita nt 
pla n ne d a blati o n t o hel p e ns ure bal a nce of treat me nt assi g n me nts wit hi n t he 
se q ue ntial a n d c o n c o mita nt gr o u ps. 
F oll o w -U p 
Sc he d ule  
St u d y pr oce d ures a n d f oll o w -u p visits will occ ur as f oll o ws:  
•  C o nse nt –  M ust be o btai ne d wit hi n 3 0 da ys pri or t o ra n d o mizati o n  
•  Ra n d o mizati o n  
o  Pri or a blati o n ( Se q ue ntial gr o u p) –  ra n d o mizati o n m ust be 
perf or me d b et wee n 9 0 a n d 1 8 0 da ys after t he m ost rece nt A F 
a blati o n pr oce d ure . W A T C H M A N F L X  I m pl a nt –  m ust be 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 1  of 1 0 2  
  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
perf or me d wit hi n 1 0 da ys f oll o wi n g ra n d o mizati o n if s u bject 
is ra n d o mize d t o t he de vi ce ar m 
o  Pla n ne d pr os pecti ve a blati o n ( C o nc o mita nt gr o u p) –  t he 
a blati o n +/ ̶ W A T C H M A N  F L X  I m pla nt m ust be perf or me d 
wit hi n 1 0 da ys  of ra n d o mizati o n   
•  3 M o nt h F oll o w -u p ( 9 0 ± 1 5 da ys fr o m ra n d o mizati o n)  
•  1 2 -M o nt h F oll o w -u p ( 3 6 5 ± 3 0 da ys fr o m ra n d o mizati o n) 
•  2 4 -M o nt h F oll o w -u p ( 7 3 0 ± 6 0 da ys fr o m ra n d o mizati o n)  
•  3 6 -M o nt h F oll o w -u p ( 1 0 9 5 + 6 0  da ys fr o m r a n d o mizati o n)  –  t his 
f oll o w-u p m ust  occ ur o n or after 1 0 9 5 da ys  a n d o n or bef ore 1 1 5 5 
da ys  
N ote: f or R oll -i n s u bjects t he date of i m pla nt will be use d t o calc ul ate 
F oll o w -u p wi n d o ws i nstea d of t he date of ra n d o mi zati o n.  
St u d y D ur ati o n  
T he d urati o n of t he st u d y is e x pecte d t o last a p pr o xi matel y 6 4  m o nt hs. T he 
d urati o n of i n di vi d ual s u bject partici pati o n is e x pecte d t o last a p pr o xi matel y 3 6 
m o nt hs b ut ma y var y per s u bject.  
C o ntr ol Gr o u p 
Me dic ati o n 
T her a p y  
F oll o wi n g ra n d o mizati o n, c o ntr ol s u bjects m ust  c o nti n ue or start mar ket -
a p pr o ve d O A C use d per I F U f or atrial fi brillati o n str o ke pre ve nti o n  a n d 
s h o ul d re mai n o n it f or t he d urati o n of t he trial. 
De vice Gr o u p 
Me dic ati o n 
T her a p y  
After t he W A T C H M A N F L X i m pla nt, De vice Gr o u p s u bjects will be 
prescri be d mar ket -a p pr o ve d O A C a n d as piri n ( 7 5 -1 0 0 m g rec o m me n de d) u ntil 
t he 3-m o nt h visit  f oll o we d b y as piri n u ntil  at least t he 1 2 -m o nt h  visit  
(rec o m me n de d f or d urati o n of t he trial). 
Test De vice a n d 
sizes 
T he W A T C H M A N F L X Left Atrial A p pe n d a ge Cl os ure De vice wit h 
Deli ver y S yste m (c o nsisti n g of t he Deli ver y Cat heter wit h a pre -l oa de d 
Cl os ure De vice)  
W A T C H M A N F L X is a vaila ble i n 2 0, 2 4, 2 7, 3 1, a n d 3 5 m m m o dels t o fit 
left atrial a p pe n d a ge osti a wi dt hs ra n gi n g fr o m 1 4. 0 - 3 1. 5 m m.  
I ncl usi o n 
Criteri a  
1.  T he s u bject is of le gal a g e t o partici pate i n t he st u d y per t he la ws of 
t heir res pecti ve ge o gra p h y.  
2.  U n der we nt a pri or cat het er a blati o n pr o ce d ure f or n o n -val v ular A F 
bet wee n 9 0 a n d 1 8 0  da ys pri or t o ra n d o mizati o n (se q ue ntial) or is 
pla n ni n g t o ha ve  cli nicall y i n dicate d  cat het er a bl ati o n wit hi n 1 0  da ys 
of ra n d o mizati o n (c o nc o mita nt).   
3.  T he s u bject has a calc ul ate d C H A 2 D S 2 -V A Sc sc ore of 2 or great er 
f or males or 3 or greater f or fe mal es. 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 2  of 1 0 2  
  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
4.  T he s u bject is dee me d b y t he treati n g p h ysicia n t o be s uita ble f or t he 
pr ot oc ol defi ne d p h ar mac ol o gic re gi me n s. 
5.  T he s u bject is a ble t o u n der g o T E E e x a mi nati o ns.  
6.  T he s u bject or le g al re prese ntati ve is a ble t o u n dersta n d a n d is 
willi n g t o pr o vi de writte n i nf or me d c o nse nt t o partici pate i n t he trial.  
7.  T he s u bject is a ble a n d willi n g t o ret ur n f or re q uir e d f oll o w -u p visits 
a n d e xa mi nati o ns.  
E xcl usi o n 
Criteri a  
1.  T he s u bject is c urre ntl y e nr olle d i n a n ot her i n vesti gati o nal st u d y t hat 
w o ul d directl y i nterfere wit h t he c urre nt st u d y, e x ce pt w he n t he 
s u bject is partici pati n g i n a ma n dat or y g o ver n me ntal re gistr y, or a 
p urel y o bser vati o nal re gistr y wit h n o ass ociate d tr eat me nts. Eac h 
i nsta nce m ust be br o u g ht t o t he atte nti o n of t he s p o ns or t o deter mi ne 
eli gi bilit y, re gar dless of t y pe of c o -e nr oll me nt bei n g pr o p ose d.  
2.  T he s u bject re q uires l o n g -ter m a ntic oa g ulati o n t hera p y f or reas o ns 
ot her t ha n A F -relate d str o ke ris k re d ucti o n, f or e x a m ple d ue t o a n 
u n derl yi n g h y perc o a g ula ble state (i.e., e v e n if t he de vice is 
i m pla nte d, t he s u bjects w o ul d n ot be eli gi ble t o disc o nti n ue O A C d ue 
t o ot her me dical c o n diti o ns re q uiri n g c hr o nic O A C t hera p y).  
3.  T he s u bject is dee me d b y t he treati n g p h ysicia n t o be u ns uita ble f or 
c hr o nic antic o a g ulati o n a n d/ or as piri n t hera p y  d u e t o blee di n g ris k, 
aller g y, or ot her reas o ns.  
4.  T he s u bject ha d or is pla n ni n g t o ha ve a n y car diac or maj or n o n -
car diac i nter ve nti o nal or s ur gical pr oce d ure (e xcl u di n g n o n -val v ular 
A F a blati o n  a n d car di o v ersi o n ) wit hi n 3 0 da ys pri or t o or 6 0 da ys 
after ra n d o mizati o n [i ncl u di n g, b ut n ot li mite d t o: perc uta ne o us 
c or o nar y i nter ve nti o n ( P CI), ot her car diac a blati o n ( V T a blati o n, 
etc.), etc.].  
5.  T he s u bject ha d a str o ke or tra nsie nt isc he mic attac k ( TI A) wit hi n t he 
6 0 da ys pri or t o ra n d o mi zati o n.  
6.  T he s u bject ha d a pri or maj or blee di n g e ve nt p er I S T H d efi niti o n 
wit hi n t he 1 4 da ys pri or t o ra n d o mizati o n. Lac k of res ol uti o n of 
relate d cli nical se q uelae, or pla n ne d a n d p e n di n g i nter ve nti o ns t o 
res ol ve blee di n g/ blee di n g s o urce, are a f urt her e x cl usi o n re gar dless 
of ti mi n g of t he blee di n g e ve nt.  
7.  T he s u bject has ha d a m y ocar dial i nfarcti o n ( MI) d oc u me nte d i n t he 
cli nical rec or d as eit her a n o n -S T ele vati o n MI ( N S T E MI) or as a n 
S T -ele vati o n MI ( S T E MI), wit h or wit h o ut i nter ve nti o n, wit hi n 9 0 
da ys pri or t o ra n d o mizati o n.  
8.  T he s u bject has a hist or y of atrial se ptal r e pair or has a n A S D/ P F O 
de vice.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 3  of 1 0 2  
  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
9.  T he s u bject has a n i m pla nte d mec ha nical val ve pr ost hesis i n a n y 
p ositi o n.  
1 0.  T he s u bject is of c hil d beari n g p ote ntial a n d is, or pla ns t o bec o me 
pre g na nt d uri n g t he ti me of t he st u d y ( met h o d of assess me nt u p o n 
st u d y p h ysicia n’s discreti o n)  
1 1.  T he s u bject has a d o c u m e nte d life e x p ecta nc y of l ess t ha n t w o years.  
1 2.  T he s u bject has a car diac t u m or.  
1 3.  T he s u bject has si g ns/s y m pt o ms of ac ute or c hr o nic pericar ditis.  
1 4.  T here is e vi de n ce of ta m p o na de p h ysi ol o g y.  
1 5.  T he s u bject has c o ntrai n dicati o ns (a nat o mical or me dical) t o 
perc uta n e o us cat h eterizati o n pr oce d ures . 
1 6.  T he s u bject has d oc u m e nte d N Y H A Class I V heart fail ure . 
1 7.  T he s u bject has d oc u m e nte d s ur gical cl os ure of t h e left atrial 
a p pe n da g e.  
1 8.  T he s u bject has a n acti ve i nfecti o n.  
Tr a nst h or acic 
Ec h o  E xcl usi o n 
Criteri a  
1.  T he s u bject has L V E F < 3 0 %  
2.  T he s u bject has a n e xisti n g pericar dial eff usi o n wit h a circ u mfere ntial 
ec h o-free s p ace > 5 m m.  
3.  T he s u bject has a hi g h - ris k pate nt f ora me n o vale ( P F O) wit h a n atri al 
se ptal a ne ur ys m e x c ursi o n > 1 5 m m or le n gt h > 1 5 m m.  
4.  T he s u bject has a hi g h -ris k P F O wit h a lar ge s h u nt defi ne d as earl y, 
wit hi n 3 beats a n d/ or s u bsta ntial passa ge of b u b bl es.  
5.  T he s u bject has si g nifica nt mitral val ve ste n osis (i.e., M V  area < 1. 5 
c m
2).  
N ote: Criteria o btai ne d fr o m car diac i ma gi n g perf or me d wit hi n 1 8 0 da ys pri or 
t o ra n d o mizati o n ma y be use d if all t he e xcl usi o n criteria ca n be e val uate d. 
M ulti ple 
I nter ve nti o ns 
D uri n g I n de x 
Pr oce d ure  
P erc uta ne o us  cat heter a bl ati o n usi n g c urre ntl y a vaila ble  n o n -s ur gical 
sta n dar d tec h ni q u es a n d mar ket-a p pr o ve d tec h n ol o g y  ma y  be perf or me d at 
t he ti me of t he W A T C H M A N F L X  i m pla nt pr o ce d ure o nl y  f or 
C o nc o mit a nt  A bl ati o n s u bjects    
 
• 
T he pr oce d ures m ust oc c ur o n t he sa me da y wit h t he a blati o n 
occ urri n g pri or t o t he W A T C H M A N F L X i m pla nt .  
• 
Cat heter  a blati o n of t he L A A , n o n -sta n dar d a blati o n tec h ni q ues (e. g. 
C F A Es  a n d h y bri d a bl ati o n ) a n d a n y n o n -A F -relat e d a blati o n (e. g. 
V T) are n ot per mitte d .  
• 
Ot her c o nc o mita nt pr o ce d ures are als o n ot per mitte d, i ncl u di n g, b ut 
n ot li mite d t o, tra nsc uta ne o us val ve pr o ce d ures, p ace ma ker or I C D 
ge nerat or c ha n g e, etc.   
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 4  of 1 0 2  
  
C o m p aris o n of A n tic oa g ulati o n wit h Left Atrial A p pe n da ge Cl o s ure after A F 
A blati o n  (O P TI O N ) 
N ote: Se q ue ntial  A blati o n  s u bjects w h o nee d a re peat a blati o n ca n n ot 
c o m bi ne it wit h t he W A T C H M A N F L X i m pla nt pr oce d ure.  
F or all patie nts,  ca v otric us pi d ist h m us (C TI ) a blati o n a n d car di o v ersi o n ma y 
be perf or me d d uri n g a bl ati o n . 
St atistic al Test 
Met h o d  
H y p ot heses testi n g i n t his st u d y will use sta n dar d statistical met h o d ol o g y. 
Eac h pri mar y e n d p oi nt will be assesse d vs. a perf or ma nce g o al. T o declare 
s uccess, t he pri mar y e n d p oi nt s m ust be met. T he details of eac h e n d p oi nt 
a nal ysis are liste d i n t he t a ble bel o w.   
 
E n d p oi nt  
Assess me nt 
peri o d  
E x pecte d 
R ate  
N o n -
I nferi orit y 
M ar gi n                       
Test  
( α =2. 5 %)  NI 
( α = 5 %) S u p   
E x pecte d 
Attriti o n  
P o wer 
s u bjects  
Pri mar y 
Efficac y 
E n d p oi nt  
3 6 -m o nt h 
f oll o w-u p 
visit  
1 0 %  i n b ot h 
ar ms 
5 %  
O ne -si de d 
NI T est of 
K M e ve nt 
rates  
1 5 %  
8 4 %  
( N = 1 6 0 0) 
Pri mar y 
Safet y 
E n d p oi nt  
3 6 -m o nt h 
f oll o w-u p 
visit  
De vice: 1 4 %  
C o ntr ol: 2 0 %  
N A  
T w o -si de d 
l o g-ra n k test 
2 0 %  
> 8 6. 4 %  
( N = 1 6 0 0) 
Sec o n dar y 
E n d p oi nt   
3 6 -m o nt h 
f oll o w-u p 
visit  
De vice: 1 1 %  
C o ntr ol: 1 1 %   
5. 2 5 %  
O ne -si de d 
NI T est of 
K M e ve nt 
rates  
2 0 %  
8 4. 3 % 
( N = 1 6 0 0)     
 
 
 
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 5  of 1 0 2  
  
3.  T a ble of C o nte nts  
1.  T I T L E P A G E  .......................................................................................................................1  
2.  
P R O T O C O L S Y N O P SI S  .........................................................................................................9  
3.  
T A B L E O F C O N T E N T S  .......................................................................................................1 5  
3. 1.  T a ble of Fi g ures  .....................................................................................................2 1  
3. 2.  T a ble of T a bles  ......................................................................................................2 1  
4.  
IN T R O D U C TI O N .................................................................................................................2 2  
4. 1.  B ac k gr o u n d  ............................................................................................................2 2  
4. 2.  W A T C H M A N T her a p y  ........................................................................................2 3  
4. 3.  St u d y R ati o n ale  .....................................................................................................3 1  
5.  
D E VI C E D E S C RI P TI O N  ......................................................................................................3 1  
6.  
S T U D Y O B J E C TI V E  ...........................................................................................................3 6  
7.  
S T U D Y E N D P OI N T S  ...........................................................................................................3 6  
7. 1.  Pri m ar y Effecti v e ness E n d p oi nt  ..........................................................................3 6  
7. 2.  Pri m ar y S afet y E n d p oi nt  ......................................................................................3 6  
7. 3.  Sec o n d ar y E n d p oi nt  ..............................................................................................3 6  
7. 4.  A d diti o n al A n al yses  ..............................................................................................3 6  
8.  
S T U D Y D E SI G N  .................................................................................................................3 7  
8. 1.  Sc ale a n d D ur ati o n  ................................................................................................3 8  
8. 2.  Tre at me nt Assi g n me nt  ..........................................................................................3 8  
8. 2. 1.  
De vice Gr o u p Treat me nt  ..........................................................................3 8  
8. 2. 2.  
C o ntr ol Gr o u p Treat me nt  .........................................................................3 9  
8. 3.  J ustific ati o n f or t he St u d y Desi g n  ........................................................................3 9  
9.  
S U B J E C T S E L E C TI O N  ........................................................................................................3 9  
9. 1.  St u d y P o p ul ati o n a n d Eli gi bilit y  ..........................................................................3 9  
9. 2.  I ncl usi o n Criteri a ..................................................................................................4 0  
9. 3.  E xcl usi o n Criteri a  .................................................................................................4 0  
9. 4.  Tr a nst h or acic Ec h oc ar di o gr a p hic E xcl usi o n Criteri a  ......................................4 2  
1 0.  S U B J E C T A C C O U N T A BI LI T Y  .............................................................................................4 2  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 6  of 1 0 2  
  
1 0. 1.  P oi nt of E nr oll me nt  ...............................................................................................4 2  
1 0. 2.  S u bject St at us a n d Cl assific ati o n  .........................................................................4 2  
1 0. 2. 1.  Scree n Fail ure  ...........................................................................................4 2  
1 0. 2. 2.  Ra n d o mize d  ..............................................................................................4 3  
1 0. 2. 3.  De vice Gr o u p Classificati o ns  ...................................................................4 3  
1 0. 2. 3. 1.  I nte nt ........................................................................................4 3  
1 0. 2. 3. 2.  Atte m pt  ....................................................................................4 4  
1 0. 2. 3. 3.  I m pla nt .....................................................................................4 4  
1 0. 3.  St u d y C o m pleti o n, Wit h dr a w al, or L ost t o F oll o w -U p  .....................................4 4  
1 0. 4.  E n d of St u d y Acti o n Pl a n  .....................................................................................4 5  
1 1.  S T U D Y M
E T H O D S  .............................................................................................................4 5  
1 1. 1.  D at a C ollecti o n –  R oll -I n S u bjects.......................................................................4 5  
1 1. 2.  D at a C ollecti o n –  R a n d o mize d S u bjects  .............................................................4 6  
1 1. 3.  St u d y C a n di d ate Scree ni n g  ..................................................................................4 9  
1 1. 4.  I nf or me d C o nse nt..................................................................................................4 9  
1 1. 5.  B aseli ne Assess m e nt Wi n d o w  ...............................................................................4 9  
1 1. 6.  R a n d o miz ati o n .......................................................................................................5 0  
1 1. 6. 1.  Se q ue ntial A blati o n gr o u p  ........................................................................5 0  
1 1. 6. 2.  C o nc o mita nt A blati o n gr o u p  ....................................................................5 0  
1 1. 7.  I n de x Pr oce d ure ....................................................................................................5 0  
1 1. 8.  St u d y Me dic ati o n Re gi m e n  ..................................................................................5 2  
1 1. 8. 1.  De vice Gr o u p St u d y Me dicati o n Re gi me n  ...............................................5 2  
1 1. 8. 2.  C o ntr ol Gr o u p St u d y Me dicati o n Re gi me n  ..............................................5 2  
1 1. 9.  F oll o w -U p Pr oce d ures ( Office( preferre d) or P h o ne c all)  ..................................5 2  
1 1. 1 0.  
L A A I m a gi n g ( T E E, I C E, a n d C T)  .......................................................5 3  
1 1. 1 0. 1.  Baseli ne Tra nst h oracic Ec h ocar di o gra m ( T T E)  .......................................5 3  
1 1. 1 0. 2.  I m pla nt a n d F oll o w-U p I ma gi n g ( T E E/I C E/ C T)  .....................................5 4  
1 1. 1 1.  
Str o ke or S yste mic E m b olis m  ................................................................5 4  
1 1. 1 1. 1.  Str o ke Scales  .............................................................................................5 4  
1 1. 1 1. 2.  Str o ke or S yste mic E m b olis m a n d L A A I ma gi n g ( All s u bjects)  .............5 5  
1 1. 1 2.  
De vice T hr o m b us  ....................................................................................5 5  
1 1. 1 3.  
De vice Se al  ...............................................................................................5 6  
1 1. 1 4.  
St u d y C o m pleti o n  ...................................................................................5 6  
1 1. 1 5.  
S o urce D oc u me nts  ..................................................................................5 7  

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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
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1 1. 1 6.  
L oc al L a b or at or y  ....................................................................................5 8  
1 2.  C O N T R O L G R O U P C R O S S O V E R  ........................................................................................5 8  
1 3.  S T A TI S TI C A L C O N SI D E R A TI O N S  ......................................................................................5 8  
1 3. 1.  E n d p oi nts  ...............................................................................................................5 8  
1 3. 1. 1.  Pri mar y Efficac y E n d p oi nt  .......................................................................5 8  
1 3. 1. 1. 1.  H y p ot heses  ...............................................................................5 8  
1 3. 1. 1. 2.  Sa m ple Size  ..............................................................................5 9  
1 3. 1. 1. 3.  Statistical Met h o ds  ...................................................................5 9  
1 3. 1. 2.  Pri mar y Safet y E n d p oi nt  ...........................................................................6 0  
1 3. 1. 2. 1.  H y p ot heses  ...............................................................................6 0  
1 3. 1. 2. 2.  Sa m ple Size  ..............................................................................6 0  
1 3. 1. 2. 3.  Statistical Met h o ds  ...................................................................6 1  
1 3. 1. 3.  Sec o n dar y E n d p oi nt  ..................................................................................6 1  
1 3. 1. 3. 1.  H y p ot heses  ...............................................................................6 1  
1 3. 1. 3. 2.  Sa m ple Size  ..............................................................................6 1  
1 3. 1. 3. 3.  Statistical Met h o ds  ...................................................................6 2  
1 3. 2.  Ge ner al St atistic al Met h o ds  .................................................................................6 2  
1 3. 2. 1.  A nal ysis Sets  .............................................................................................6 2  
1 3. 2. 2.  C o ntr ol of S yste matic Err or/ Bias  ..............................................................6 2  
1 3. 2. 3.  N u m ber of S u bjects per I n vesti gati ve Site  ...............................................6 2  
1 3. 3.  D at a A n al yses  ........................................................................................................6 3  
1 3. 3. 1.  Descri pti o n of Baseli ne Varia bles  ............................................................6 3  
1 3. 3. 2.  A d diti o nal E n d p oi nts/ Meas ure me nts  ........................................................6 3  
1 3. 3. 3.  S u b gr o u p A nal yses  ...................................................................................6 4  
1 3. 3. 4.  J ustificati o n of P o oli n g .............................................................................6 4  
1 3. 3. 4. 1.  P o oli n g of I n vesti gati o nal Ce nters  ...........................................6 4  
1 3. 3. 5.  M ulti varia ble A nal yses  .............................................................................6 5  
1 3. 3. 6.  Se nsiti vit y A nal yses f or t he Pri mar y E n d p oi nts  .......................................6 5  
1 3. 3. 7.  Missi n g Data  .............................................................................................6 5  
1 3. 3. 8.  Ot her A nal yses  ..........................................................................................6 5  
1 3. 3. 9.  I nteri m A nal yses .......................................................................................6 6  
1 3. 3. 1 0.  C ha n ges t o Pla n ne d A nal yses  ...................................................................6 6  
1 4.  H E A L T H E C O N O MI C S O U T C O M E S  ...................................................................................6 6  
1 5.  D A T A M
A N A G E M E N T  .......................................................................................................6 6  
1 5. 1.  D at a C ollecti o n, Pr o cessi n g, a n d Re vie w  ............................................................6 6  
1 5. 2.  D at a Rete nti o n  .......................................................................................................6 7  

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 8  of 1 0 2  
  
1 5. 3.  C ore L a b or at ori es  .................................................................................................6 7  
1 6.  D E VI A TI O N S ......................................................................................................................6 8  
1 7.  D E VI C E / EQ UI P M E N T A C C O U N T A BI LI T Y  .........................................................................6 8  
1 7. 1.  C o m merci al E q ui p me nt  ........................................................................................6 8  
1 7. 2.  I n vesti g ati o n al E q ui p me nt ...................................................................................6 8  
1 8.  C O M P LI A N C E  ....................................................................................................................6 9  
1 8. 1.  St ate me nt of C o m pli a nce  ......................................................................................6 9  
1 8. 2.  I n vesti g at or Res p o nsi bilities ................................................................................7 0  
1 8. 2. 1.  Dele gati o n of Res p o nsi bilit y  ....................................................................7 1  
1 8. 3.  I nstit uti o n al Re vie w B o ar d/ Et hics C o m mittee ..................................................7 2  
1 8. 4.  S p o ns or Res p o nsi bilities  .......................................................................................7 2  
1 8. 4. 1.  R ole of B ost o n Scie ntific Re prese ntati ves  ...............................................7 3  
1 8. 5.  I ns ur a nce ................................................................................................................7 3  
1 9.  M
O NI T O RI N G  ....................................................................................................................7 3  
2 0.  P O T E N TI A L R I S K S A N D B E N E FI T S  ...................................................................................7 4  
2 0. 1.  A ntici p ate d A d verse E v e nts  .................................................................................7 4  
2 0. 2.  A ntici p ate d A d verse D e vice Effects  .....................................................................7 5  
2 0. 3.  Ris ks Ass oci ate d wit h t he St u d y De vice  ..............................................................7 5  
2 0. 4.  Ris ks ass oci ate d wit h P artici p ati o n i n t he Cli nic al St u d y  .................................7 5  
2 0. 5.  Me dic ati o n Ris ks  ...................................................................................................7 6  
2 0. 6.  Ris k Mi ni miz ati o n Acti o ns  ...................................................................................7 6  
2 0. 7.  A ntici p ate d Be nefits  ..............................................................................................7 6  
2 0. 8.  Ris k t o Be nefit R ati o n ale  ......................................................................................7 6  
2 1.  S A F E T Y R E P O R TI N G  .........................................................................................................7 7  
2 1. 1.  Re p ort a ble E ve nts b y i n vesti g ati o n al site t o B ost o n Scie ntific  .........................7 7  
2 1. 2.  Defi niti o ns a n d Cl assific ati o n ...............................................................................7 8  
2 1. 3.  Rel ati o ns hi p t o St u d y De vice(s)  ...........................................................................8 0  
2 1. 4.  I n vesti g at or Re p orti n g Re q uire me nts .................................................................8 2  
2 1. 5.  B ost o n Scie ntific De vice Deficie ncies  ...................................................................8 4  
2 1. 6.  Re p orti n g t o Re g ul at or y A ut h orities / I R Bs / E Cs / R E Bs/ I n vesti g at ors  .......8 4  

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
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2 1. 7.  S u bject De at h Re p orti n g  ......................................................................................8 4  
2 2.  IN F O R M E D C O N S E N T  ........................................................................................................8 5  
2 3.  C O M MI T T E E S  ...................................................................................................................8 6  
2 3. 1.  S afet y M o nit ori n g Pr ocess  ....................................................................................8 6  
2 3. 2.  Steeri n g C o m mittee  ...............................................................................................8 6  
2 3. 3.  Cli nic al E ve nts C o m mittee  ...................................................................................8 7  
2 3. 4.  D at a M o nit ori n g C o m mittee  ................................................................................8 7  
2 4.  S U S P E N SI O N O R T E R MI N A TI O N ........................................................................................8 7  
2 2. 1  Pre m at ure Ter mi n ati o n of t he St u d y  ..................................................................8 7  
2 2. 1. 1  
Criteria f or Pre m at ure T er mi nati o n of t he St u d y  ......................................8 8  
2 2. 2  Ter mi n ati o n of St u d y P artici p ati o n b y t he I n vesti g at or or Wit h dr a w al of 
I R B/ E C / R E B A p pr o v al ......................................................................................8 8  
2 2. 3. Re q uire me nts f or D oc u me nt ati o n a n d S u bject F oll o w -u p  ................................8 8  
2 2. 4  Criteri a f or S us pe n di n g/ Ter mi n ati n g a St u d y Site  ............................................8 9  
2 5.  S T U D Y R E GI S T R A TI O N A N D R E S U L T S  .............................................................................8 9  
2 5. 1.  St u d y Re gistr ati o n  .................................................................................................8 9  
2 5. 2.  Cli nic al I n vesti g ati o n Re p ort  ...............................................................................8 9  
2 6.  P U B LI C A TI O N P O LI C Y  ......................................................................................................8 9  
2 7.  R EI M B U R S E M E N T A N D C O M P E N S A TI O N F O R S U B J E C T S  .................................................9 0  
2 7. 1.  S u bject Rei m b urse me nt  ........................................................................................9 0  
2 7. 2.  C o m pe ns ati o n f or S u bject’s He alt h I nj ur y .........................................................9 0  
2 8.  B I B LI O G R A P H Y .................................................................................................................9 0  
2 9.  A B B R E VI A TI O N S A N D D E FI NI TI O N S  .................................................................................9 3  
2 9. 1.  A b bre vi ati o ns .........................................................................................................9 3  
2 9. 2.  Defi niti o ns  ..............................................................................................................9 6  
2 9. 2. 1.  Val v ular Atrial Fi brillati o n  .......................................................................9 6  
2 9. 2. 2.  N o n -Val v ular Atrial Fi brillati o n  ...............................................................9 6  
2 9. 2. 3.  Blee di n g defi niti o ns  ..................................................................................9 6  
2 9. 2. 3. 1.  Blee di n g Aca de mic R esearc h C o ns orti u m ( B A R C)  ................9 6  
2 9. 2. 3. 2.  I S T H .........................................................................................9 7  
2 9. 2. 4.  Car diac Perf orati o n  ...................................................................................9 8  

C o nfi de ntial  
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2 9. 2. 5.  Left Ve ntric ul ar ( L V) D ysf u ncti o n  ...........................................................9 8  
2 9. 2. 6.  M ortalit y  ...................................................................................................9 8  
2 9. 2. 7.  Str o ke/ TI A defi niti o ns  ..............................................................................9 9  
2 9. 2. 8.  S yste mic E m b olis m  ................................................................................1 0 1  
2 9. 2. 9.  Pr oce d ure relate d C o m plicati o ns  ............................................................1 0 1  
2 9. 2. 1 0.  Oral A ntic oa g ula nt C o m plia nce  .............................................................1 0 2  
 
 
 

C o nfi de ntial  
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3. 1.  T a ble of Fi g ures  
Fi g ure 1: W A T C H M A N Deli ver y S yste m ( Deli ver y Cat heter & L A A Cl os ure De vice)  ...... 3 2  
Fi g ure 2: W A T C H M A N Access S yste m  ................................................................................ 3 5  
Fi g ure 3: W A T C H M A N Tr u Seal Access S yste m  .................................................................. 3 5  
Fi g ure 4: St u d y Fl o w Dia gra m  ............................................................................................... 3 9  
 
3. 2.  T a ble of T a bles  
Ta ble 4. 1: Descri pti o n of W A T C H M A N Pr o d ucts  ................................................................ 2 3  
Ta ble 4. 2: Cli nical St u dies of t he W A T C H M A N T M  or W A T C H M A N F L X T M  De vice  ........ 2 4  
Ta ble 9. 2 -1: I ncl usi o n Criteria  ................................................................................................ 4 0  
Ta ble 9. 3 -1: E xcl usi o n Criteria  ............................................................................................... 4 1  
Ta ble 9. 4 -1: Tr a nst h oraci c Ec h o E xcl usi o n Criteri a  ............................................................... 4 2  
Ta ble 1 1. 1 -1: R oll -I n St u d y Visits .......................................................................................... 4 5  
Ta ble 1 1. 2 -1: Ra n d o mize d S u bject St u d y Visits  .................................................................... 4 6  
Ta ble 1 1. 2 -2: Dat a C ollecti o n Sc he d ule  ................................................................................. 4 7  
Ta ble 1 1. 1 4 -1: St u d y E xit Data C ollecti o n Re q uire me nts  ...................................................... 5 6  
Ta ble 2 0. 1 -1: A ntici pate d A d verse E v e nts  ............................................................................. 7 4  
Ta ble 2 1. 2 -1: Safet y D efi niti o ns  ............................................................................................. 7 8  
Ta ble 2 1. 3 -1: Criteria f or Assessi n g Relati o ns hi p of St u d y De vice, C o m parat or, Pr oce d ure t o 
A d verse E v e nt  ...................................................................................................... 8 1  
Ta ble 2 1. 4 -1: I n vesti gat or Re p orti n g Re q uire me nts ............................................................... 8 2  
Ta ble 2 9. 1 -1 : A b bre viati o ns ................................................................................................... 9 4  
 
 
 

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
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4.  I ntr o d ucti o n 
4. 1.  B ac k gr o u n d  
Atrial fi brillati o n ( A F) is o ne of t he m ost c o m m o n a b n or mal r h yt h m dist ur ba nces a n d affects 
a p pr o xi matel y 5. 5 milli o n pe o ple w orl d wi de, i ncl u di n g 1 0 % of pe o ple ol d er t ha n 7 5 1years. 
T here are ma n y fact ors t hat ca use a n d s ustai n atri al fi brillati o n ma ki n g treat me nt strate gies 
diffic ult f or cli nicia ns. S y m pt o ms of A F ca n b e mi n or  t o se vere. T h e m ost de bilitati n g 
c o nse q ue nce of A F is t hr o m b us f or mati o n fr o m sta g na nt bl o o d fl o w lea di n g t o 
t hr o m b oe m b olis m a n d str o ke.  As s uc h, t he rate of isc he mic str o ke attri b ute d t o n o n-val v ular 
A F is esti mate d t o a vera g e 5 % per year, w hic h is 2 -7 ti mes t hat o f t h ose wit h o ut A F2. T h us, 
t hr o m b oe m b olic pr otecti o n i n patie nts wit h A F at hi g h ris k of str o ke is ce ntral t o treat me nt.  
Treat me nt wit h warfari n t hera p y f or t h e pre v e nti o n of t hr o m b oe m b oli ori gi nati n g i n t he left 
atrial a p pe n d a ge has b ee n well d oc u me nte d 3 -5. Warfari n t hera p y t ar geti n g a n I nter n ati o nal 
N or malize d Rati o (I N R) bet wee n 2. 0 –  3. 0 h as bee n c o nsi dere d t he g ol d sta n dar d treat me nt 
hist oricall y f or patie nts wit h n o n -val v ular A F f or pre ve nti o n of str o ke.  W hile warfari n has 
re mai ne d t he o pti m u m treat ment f or ma n y years, t here are n u mer o us c halle n ges wit h t he 
dr u g, s uc h as fre q ue nt n ee d f or m o nit ori n g a n d d osa ge a dj ust me nts, dietar y a n d meta b olic 
i nteracti o ns, a n d c o n cer ns of patie nt c o m plia nce.  A d diti o nall y, t he p ote ntial f or fre q ue nt a n d 
fatal blee di ng are hi g h c o ncer ns f or patie nts a n d care gi vers, a n d ofte n it is f o u n d t his dr u g is 
n ot well t olerate d  6 , 7.  
C urre ntl y a vaila ble alter nati ves t o warfari n are t he direct  oral a ntic oa g ula nts ( D O A Cs), 
w hic h i ncl u de da bi gatra n, ri var o xa b a n, a pi xa ba n, a n d e d o xa b a n. U nli ke warfari n, D O A Cs 
ca n be a d mi nistere d wit h o ut t he nee d f or m o nit ori n g, ha ve fe wer f o o d a n d dr u g i nteracti o ns, 
a n d pr o vi de a n i m pr o ve d effecti ve ness/safet y rati o. Da bi gatra n at t he d ose of 1 5 0 m g t wice 
dail y is s h o w n t o be s u peri or t o warfari n i n pre v e nti o n of str o ke a n d s yste mic 
t hr o m b oe m b olis m, has a fa v ora bl e safet y pr ofile i ncl u di n g si g nifica ntl y less i ntracra nial 
blee di n g a n d c o m para ble e xtracra nial blee di n g, a n d is ass ociate d wit h less car di o vas c ular 
m ortalit y 7 -1 0. Ri var o xa ba n at a dail y d ose of 2 0 m g is s h o w n t o be n o ni nferi or t o warfari n i n 
pre ve nti o n of str o ke or s yste mic e m b olis m. T he ris k of maj or blee di n g is n ot si g nifica ntl y 
differe nt f or ri var o xa ba n vers us warfari n; h o w e ver, i ntracra ni al a n d fat al blee di n g is less 
fre q ue nt wit h ri var o xa b a n 1 1. I n c o m paris o n t o warfari n, a pi x a ba n at a d ose of 5 m g t wice 
dail y is als o s h o w n t o be s u peri or i n pre v e nti o n of str o ke a n d s yste mic t hr o m b oe m b olis m, 
ca uses less blee di n g, a n d is ass ociate d wit h a l o wer m ortalit y rate 1 2. E d o xa ba n is s h o w n t o 
be n o n -i nferi or t o warfari n wit h res pect t o t he pre v e nti o n of str o ke or s yste mic e m b olis m, 
a n d is ass ociate d wit h si g nifica ntl y l o wer rates of blee di n g a n d deat h fr o m car di o vas c ular 
ca uses 1 3. W hile D O A Cs si g nifica ntl y re d uce t h e n ee d f or fre q u e nt m o nit ori n g, d osa ge 
a dj ust me nts, a n d dietar y a n d meta b olic i nteracti o ns , t here are still c o ncer ns of patie nt 
c o m plia nce a n d bl ee di n g c o m plicati o ns wit h t hese ne wer a ge nts.  
 
A d diti o nall y, patie nts i n A F ma y see k s y m pt o m relief t hr o u g h car diac a blati o n treat me nt i n 
a n eff ort t o mai ntai n n or mal si n us r h yt h m.  W hile car diac a blati o n ca n be effecti ve at 
re d uci n g t he s y m pt o ms ass ociate d wit h t he arr h yt h mia, O A C is still rec o m me n de d. B ot h t he 
A C C/ A H A/ H R S a n d E S C G ui deli nes c urre ntl y rec o m me n d c o nti n ue d O A C after a n A F 

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
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cat heter a blati o n pr oce d ure f or p atie nts at ris k f or str o ke. T he 2 0 1 7 H R S A F c o nse ns us 
d oc u me nt pr o vi des rati o n ale f or w h y a ntic oa g ulati o n s h o ul d n ot be st o p pe d p ost a blati o n : 
1.  Rec urre n ces of A F are c o m m o n b ot h earl y a n d late f oll o wi n g A F a blati o n  
2.  As y m pt o matic A F is c o m m o n, a n d is m ore c o m m o n f oll o wi n g A F a blati o n t ha n pri or 
t o A F a blati o n 
3.  A F a blati o n destr o ys a p orti o n of t he atria a n d t h e i m pact of t his o n str o ke ris k is 
u ncertai n  
4.  T here h a ve bee n n o lar g e, ra n d o mize d pr os p ecti ve trials t hat ha ve assess e d t he safet y 
of disc o nti n ui n g O A C i n p ost -A blati o n patie nts  
5.  St u dies ha ve s h o w n t hat str o kes i n patie nts wit h A F mi g ht n ot be relate d t o a n A F 
e ve nt  
Des pite t he a b o ve, m a n y patie nts desire t o st o p O A C after cat heter a blati o n beca use t h e y are 
n o l o n ger s y m pt o matic.  
 
As t he ris k of str o ke i ncreases wit h a g e a n d t he disa bilit y a n d t olera nce c o ncer ns wit h 
a vaila ble dr u g t hera p y p ersist, t he nee d f or p er ma n e nt pr otecti o n a gai nst t hr o m b oe m b olis m 
i n A F patie nts re m ai ns u n met. T he s p o ns or de vel o pe d t he W A T C H M A NT M  a n d 
W A T C H M A N F L X
T M  Left Atrial A p pe n d a ge Cl os ure ( L A A C) De vice, a p er ma ne nt 
i m pla nta ble de vice t o se al off t he left atrial a p pe n d a ge, t he l ocati o n w here t he vast maj orit y 
of t hr o m bi ori gi nate i n A F patie nts.  T his de vice h as bee n s h o w n t o  pr o vi d e a n alter nati ve t o 
wa rfari n t hera p y i n n o n-val v ular A F patie nts w h o re q uire t hr o m b oe m b olic pr otecti o n. T he 
c urre nt st u d y is desi g ne d t o deter mi ne if left atri al a p pe n da g e cl os ure wit h t he W A T C H M A N 
F L X D e vice is a reas o n a ble alter nati ve t o or al a ntic oa g ulati o n , i ncl u di n g warfari n a n d t he 
direct oral a ntic oa g ula nts,  f oll o wi n g perc uta ne o us cat heter a blati o n f or n o n-val v ular atrial 
fi brillati o n. 
4. 2.  W A T C H M A N T her a py  
T w o ge nerati o ns of t he W A T C H M A N Cl os ure De vice wit h D eli ver y S yste m, as i de ntifie d i n 
t he T a ble 4. 1 , are disc usse d bel o w. T he W A T C H M A N Access S yste m (re q uire d access or y 
f or use i n W A T C H M A N pr oce d ures) a n d eac h ge nerati o n of t he W A T C H M A N Cl os ure 
De vice wit h D eli ver y S yste m are pr o vi de d st erile a n d as si n gle use de vices.  
 
T a ble 4. 1 : Descri pti o n of W A T C H M A N P r o d ucts  
N a me  
Descri pti o n  
W A T C H M A N ™ 
Access S yste m  
T he first C E -mar ke d a n d F D A -a p pr o ve d 
ge nerati o n of t he W A T C H M A N Access 
S yste m. T his Access S yste m ma y be use d 
wit h eit her t he W A T C H M A N ( Ge n 2. 5) or 
W A T C H M A N F L X Cl os ure De vice wit h 
Deli ver y S yste m  
W A T C H M A N Tr u Seal  
Access S yste m  
B ost o n Scie ntific’s ne xt C E -mar ke d a n d 
F D A -a p pr o ve d ge nerati o n W A T C H M A N 
Access  S yste m.  

C o nfi de ntial  
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N a me  
Descri pti o n  
W A T C H M A N ™ L A A 
Cl os ure De vice wit h 
Deli ver y S yste m  
T he first c o m mercialize d ge nerati o n of t he 
W A T C H M A N L A A Cl os ure De vice wit h 
Deli ver y S yste m  ( n ote: als o referre d t o 
i nter nall y as Ge n 2. 5).  
W A T C H M A N F L X ™ 
Cl os ure De vice wit h 
Deli ver y S yste m  
B ost o n Scie ntific’s ne xt ge nerati o n 
W A T C H M A N L A A Cl os ure De vice wit h 
Deli ver y S yste m.  
 
F or si m plicit y, t he t w o ge nerati o ns of t he Cl os ure De vice wit h Deli ver y S yste m will be 
refere nce d as W A T C H M A N ( Ge n 2. 5) a n d W A T C H M A N F L X a n d t he i m pla nte d p orti o n of 
t he pr o d ucts will be referre d t o as t h e Cl os ure De vi ce.  A d diti o nal ne xt ge nerati o n 
W A T C H M A N Access S yste ms  ma y bec o me a vail a ble d uri n g e nr oll me nt.  If t he y are a p pr o ve d 
or cleare d f or c o m mercial use, t he y ma y be c o nsi d ere d f or t his trial.   
 
T he i m pla nte d c o m p o ne nt of t he st u d y de vice, h ereafter referre d t o as t he W A T C H M A N F L X 
D e vice, is desi g ne d t o pre ve nt t he e m b olizati o n of t hr o m bi t hat ma y f or m i n t he L A A.  T he 
W A T C H M A N 
F L X D e vice ma y re d uce t he occ urre n ce of isc he mic str o ke a n d s yste mic 
t hr o m b oe m b olis m i n patie nts wit h n o n-val v ular A F w h o re q uire treat me nt f or p ote ntial 
t hr o m b us f or mati o n.  It ma y als o re d uce t he ris k of life-t hreate ni n g blee di n g e ve nts s uc h as 
he m o rr ha gic str o k e b y p ote ntiall y re m o vi n g t he need f or a ntic oa g ulati o n t hera p y.  
A first ge nerati o n of F L X de vice ( F L X 1. 0) was e val uate d i n a li mite d mar ket release f oll o wi n g 
C E mar k . Fee d b ac k fr o m t hat e x perie nce was  i nc or p orate d i nt o t he d esi g n of t he ne xt 
ge nerati o n F L X ( F L X 2. 0) c urre ntl y e m pl o ye d i n t his st u d y. T he c urre nt W A T C H M A N F L X 
de vice recei v e d  C E mar k  i n Fe br uar y  2 0 1 9  a n d F D A a p pr o val i n J ul y 2 0 2 0 . 
 
Vari o us cli nical trials ha ve esta blis he d t he safet y a n d perf or ma nce of t he W A T C H M A N L A A 
Cl os ure Tec h n ol o g y ( A ccess S yste m a n d Deli ver y S yste m) w hic h is d esi g ne d t o  pre v e nt 
t hr o m b us e m b olizati o n fr o m t he left atrial a p pe n da ge a n d re d u ce t he ris k of life-t hr eate ni n g 
blee di n g e ve nts i n patie nts wit h n o n -val v ular atrial fi brillati o n . T a ble 4. 2  o utli nes t he vari o us 
cli nical trials . T he E V O L V E st u d y teste d safet y a n d efficac y i n w hat was at t he ti me t he ne xt-
ge nerati o n W A T C H M A N ( Ge n 4) de vice.  T he PI N N A C L E F L X te st t he safet y a n d effi cac y 
of t he W A T C H M A N F L X de vice.  
 
T a ble 4. 2 : Cli nic al St u dies of t he W A T C H M A NT M  or W A T C H M A N F L X T M  De vice  
St u d y  
D ates of E nr oll me nt  
E nr olle d 
S u bjects  
Sites  
F oll o w -U p  
Pil ot  
(feasi bilit y st u d y) 
A u g 2 0 0 2 –  Ja n 2 0 0 5 
6 6  
8  
U. S. s u bjects c o m plete d 5 
years; O U S s u bjects 
c o m plete d u p t o 9  years.  
P R O T E C T A F  
( pi v otal st u d y) 
Fe b 2 0 0 5 –  J u n 2 0 0 8 
8 0 0  
5 9  
C o m plete t hr o u g h 5 years  
C A P Re gistr y  
A u g 2 0 0 8 –  J u n 2 0 1 0 
5 6 6  
2 6  
C o m plete  
A S A P  
Ja n 2 0 0 9 –  N o v 2 0 1 1  
1 5 0  
4  
C o m plete  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2 5  of 1 0 2  
  
St u d y  
D ates of E nr oll me nt  
E nr olle d 
S u bjects  
Sites  
F oll o w -U p  
(feasi bilit y st u d y) 
E V O L V E 
(re gistr y) 
Ma y 2 0 0 9 –  J u ne 
2 0 1 1  
6 9  
3  
C o m plete  
P R E V AI L  
( pi v otal st u d y) 
N o v 2 0 1 0 –  J u n 2 0 1 2 
4 6 1  
4 1  
C o m plete  
C A P 2 Re gistr y  
Se p 2 0 1 2 –  Mar 2 0 1 4  
5 7 9  
4 7  
C o m plete  
E W O L U TI O N 
( E U re gistr y) 
Oct 2 0 1 3 –  Ma y 2 0 1 5  
1 0 2 0  
4 7  
C o m plete  
W A S P ( Asia 
Pacific Re gistr y)  
Ja n 2 0 1 4 –  Oct 2 0 1 5  
2 0 1  
9  
C o m plete  
W A T C H M A N 
N E S Te d  
( U S P A S) 
Mar  2 0 1 6 -N o v 2 0 1 6  
2 0 0 0  
All 
c o m mercial 
sites 
F oll o w u p o n g oi n g t hr o u g h 
5  years  
S A L U T E (Ja pa n 
st u d y) 
Fe b 2 0 1 7 -J ul y 2 0 1 7 
7 1  
1 0  
C o m plete  
A S A P -T O O 
( O A C 
c o ntrai n dicate d 
p o p ulati o n)  
Fe b 2 0 1 7 -Oct 2 0 2 0  
8 8 8  
U p t o 1 3 0  
E nr oll me nt cl ose d;  f oll o w-
u p o n g oi n g t hr o u g h 5 years  
PI N N A C L E F L X  
Ma y 2 0 1 8 - N o v 2 0 1 8  
4 0 0  
2 9  
C o m plete  
F L XI BI LI T Y  
J ul 2 0 1 9 –  J ul 2 0 2 0 
3 0 0  
1 7  
O n g oi n g t hr o u g h 1 year  
I C E L A A 
J ul y 2 0 2 0-A u g 2 0 2 1  
1 0 0  
1 0  
C o m plete  
C H A M PI O N  
 
Oct 2 0 2 0 -prese nt  
3 0 0 0  
2 0 0  
O n g oi n g  
 
I n t he PI L O T st u d y, the W A T C H M A N D e vice was s uccessf ull y i m pla nte d i n 6 6/ 7 5 ( 8 8 %) 
s u bjects, wit h disc o nti n uati o n of warfari n i n 6 8 % of s u bjects  at 4 5 d a ys, 9 2 % of s u bjects b y 
si x m o nt hs, a n d 9 6 % of s u bjects  b y 6 0 m o nt hs. Mea n f oll o w -u p i n t his st u d y was 6. 1 y ears. 
T here were n o deat hs, n o de vice e m b olizati o ns relate d t o t he Cl os ure De vice , a n d n o e vi de nce 
of l o n g -ter m er osi o n. T h ese res ults s u p p orte d pr o gressi o n t o a pi v otal st u d y.  
 
T he first pi v otal st u d y, 
W A T C H M A N L eft 
Atrial 
A p pe n da g e S yste m f or E m b olic 
P R O T E C Ti o n i n Patie nts wit h Atrial Fi brillati o n 1 4  ( P R O T E C T- A F), de m o nstrate d n o n -
i nferi orit y of t he 
W A T C H M A N D e vice t o l o n g -ter m warfari n t hera p y f or t he pri mar y 
effecti ve ness e n d p oi nt of str o ke, s yste mic e m b olis m , a n d car di o vas c ular d eat h.  
 
T he p u blis he d  a nal ysis of the P R O T E C T A F 1 5  trial has s h o w n t hat t he W A T C H M A N D e vice 
ac hie ve d s u peri orit y f or t he c o m bi ne d e n d p oi nt of all str o ke, car di o vas c ular or u ne x plai ne d 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2 6  of 1 0 2  
  
deat h a n d s yste mic e m b olis m (f or Ba y esia n a nal ysis, p osteri or pr o ba bilities are us e d t o 
deter mi ne s u peri orit y; > 9 5 % re prese nts s u peri orit y).  
• T he o bser ve d pri mar y effecti ve n ess e ve nt rate was 2. 3 perce nt a n d 3. 8 perce nt i n t he 
W A T C H M A N a n d c o ntr ol gr o u ps, res pecti vel y, de m o nstrati n g a 4 0 %  perce nt relati ve ris k 
( R R) re d ucti o n i n pri mar y effecti ve ness i n t he W A T C H M A N gr o u p ( R R = 0. 6 0, p osteri or 
pr o ba bilit y of s u peri orit y = 9 6 perce nt % ). 
 
Sec o n dar y a n al ysis als o s h o we d a rel ati ve ris k re d u cti o n a n d s u peri orit y t o c o ntr ol f or all -ca us e 
m ortalit y a n d car di o vas c ular m ortalit y.  
• All-Ca use M ortalit y: t he W A T C H M A N gr o u p was s u peri or t o t he c o ntr ol gr o u p, 3. 2 %  
perce nt t o 4. 8 perce nt % res pecti vel y, re pres e nti n g a 3 4 perce nt%  rel ati ve ris k re d ucti o n 
i n all-ca use m ortalit y i n t he W A T C H M A N gr o u p ( Hazar d rati os  [ H R] = 0. 6 6, p = 0. 0 3 7 9).  
• Car di o vasc ular M ortalit y: t he W A T C H M A N gr o u p was s u peri or t o t he c o ntr ol gr o u p, 1. 0 
perce nt %  a n d 2. 4 perce nt % 
res p ecti vel y, re prese nti n g a 6 0 perce nt%  relati ve ris k 
re d ucti o n i n car di o vasc ul ar deat h i n t he W A T C H M A N gr o u p ( H R = 0. 4 0, p = 0. 0 0 4 5). 
 
T he C o nti n ue d Access t o P R O T E C T Re gistr y 1 6( C A P Re gistr y) pr o vi de d c o nti n ue d access of 
t he W A T C H M A N D e vi ce t o P R O T E C T - A F i n vesti gat ors a n d de m o nstrate d a decrease i n 
pr oce d ural c o m plicati o ns of peri car di al eff usi o n wit h ta m p o na de, car di ac  perf orati o n , a n d 
de vice e m b olizati o n ( 1. 2 %, 0. 2 %, 0 %, res pecti vel y).  
  
T he A S A Pla vi x St u d y wit h W A T C H M A N Left Atrial A p pe n da ge Cl os ur e Tec h n ol o g y 
( A S A P) st u d y was a m ulti-ce nter, pr os pecti ve n o n -ra n d o mize d st u d y of 1 5 0 s u bjects e nr olle d 
at f o ur sites i n E ur o pe. S u bjects were f oll o we d p ost -i m pla nt at 3, 6, 1 2, 1 8, a n d 2 4 m o nths. 
T he pri mar y o bje cti ve of t his st u d y was t o c haract erize t he perf or ma nce of t he 
W A T C H M A N Left Atrial A p pe n da ge ( L A A) Cl os ure De vice i n n o n -val v ul ar atrial 
fi brillati o n s u bjects f or w hic h warfari n t hera p y was c o ntrai n dicate d. T h e o v erall res ults fr o m 
t he A S A P st u d y de m o nstrate d t he f oll o wi n g:  
 
•  
Is c he mic str o ke was r e p orte d i n 3 s u bjects f or a rat e of 1. 7 per 1 0 0 pt. -yrs.  T his rate 
is si g nifica ntl y l o wer t ha n ot her trials assessi n g str o ke rat es i n s u bjects wit h atrial 
fi brillati o n w h o are u na bl e t o ta ke a ntic oa g ula nt t hera p y.   
•  
All str o ke a n d isc he mic str o ke rates i n t he A S A P st u d y were si milar t o t h ose o bser ve d 
i n t he ra n d o mize d n o n-i nferi orit y P R O T E C T A F st u d y wit h s u bjects eli gi ble f or 
warfari n t hera p y.  I n P R O T E C T A F, t he rates of all -ca use d eat h, all str o ke, a n d 
isc he mic stro ke were 3. 0, 2. 3, a n d 2. 2 e ve nts per 1 0 0 pt -yrs, res pecti vel y.  I n t he 
A S A P st u d y rates f or deat h, all str o ke, a n d isc he mic str o ke were 5. 1, 2. 3, a n d 1. 7 
e ve nts per 1 0 0 pt -yrs, res pecti vel y.  T hese rates are c o m para ble des pite s u bjects i n 
A S A P ha vi n g a hi g her C H A D S 2 str o ke ris k ( 2. 8 vs. 2. 2 i n P R O T E C T A F). 
•  
I m pla nt of t h e W A T C H M A N de vice ca n b e safel y perf or me d i n s u bjects wit h 
c o ntrai n dicati o ns t o warfari n t hera p y 1 7. 
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2 7  of 1 0 2  
  
T he sec o n d pi v otal st u d y, Pr os pecti ve Ra n d o mi ze d E v al uati o n of t he W A T C H M A N L A A 
Cl os ure De vice I n Patie nts wit h Atrial Fi brillati o n Vers us L o n g T er m 
Warfari n T h era p y 
( P R E V AI L), w as c o n d u cte d t o pr o vi de a d diti o nal i nf or mati o n o n t he i m pl a nt pr oce d ure a n d 
c om plicati o n rates ass oci ate d wit h t he de vice. 
1 8I n t his trial, L A A occl usi o n was n o n-i nferi or 
t o warfari n f or isc h e mic str o ke pre ve nti o n or s yste mic e m b olis m ( S E) > 7 d a ys’ p ost-pr oce d ure. 
Alt h o u g h n o n -i nferi orit y was n ot ac hie ve d f or o verall efficac y, e v e nt rates were l o w a n d 
n u mericall y c o m para ble i n b ot h ar ms. Pr oce d ural safet y h as si g nifica ntl y i m pr o ve d o ver t he 
pre vi o us trials, P R O T E C T A F a n d C A P. P R E V AI L o nl y data, d ata fr o m s u bjects e nr olle d i n 
t he P R E V AI L st u d y wit h o ut t he pri or P R O T E C T A F st u d y i nf or mati o n us e d i n t he Ba yesia n 
a nal ysis , s h o we d t hat the isc he mic str o ke rate ( 1. 6 7  vs. 0. 7 3  per 1 0 0 pt. -years) fa v ore d t o t he 
C o ntr ol gr o u p, w hile t he he m orr ha gic str o ke rate ( 0. 1 8  vs. 0. 5 4  per 1 0 0 pt. -years) a n d deat h 
(car di o v asc ular or u ne x plai ne d) rate ( 1.8 8  vs. 1. 9 8  per 1 0 0 pt. -y ears) fa v ore d t he 
W A T C H M A N gr o u p.  T he P R E V AI L tri al pr o vi des a d diti o nal data t hat L A A occl usi o n is a 
reas o na bl e alter nati ve t o warfari n t hera p y f or str o k e pre ve nti o n i n patie nts wit h N V A F w h o d o 
n ot ha ve a n a bs ol ute c o ntrai n dicati o n t o s h ort -ter m warfari n t hera p y.1 9 
 
T he C o nti n ue d Access Pr ot oc ol ( C A P 2) was a pr os pecti ve, n o n -ra n d o mize d, m ultice nter 
st u d y t o all o w c o nti n ue d access t o t he W A T C H M A N L A A Cl os ure T ec h n ol o g y d uri n g t he 
data a nal ysis, re p orti n g a n d re vie w of t h e P R E V AI L pi v otal st u d y Pre -M ar ket A p plicati o n b y 
F D A.  T h e first of 5 7 8 s u bjects were  e nr olle d o n 2 5 -Se p -2 0 1 2.  T he fi n al s u bjects were 
e nr olle d o n 2 1 -Mar -2 0 1 4 a n d  ha ve c o m plete d 5 years of f oll o w -u p .  S u bjects i n t his trial 
were at a hi g h -ris k of str o ke wit h a mea n C H A2D S 2-V A Sc of 4. 5 ( +/ - 1. 3).  A d diti o nall y, 
9 8 % were at m o derate t o hi g h ris k of blee di n g.  Patie nts i n t his trial ha d a n isc he mic str o ke 
rate of 2.2 p er 1 0 0 patie nt -years , w hic h is i n li ne wit h t he ot her W A T C H M A N trials.2 0    
 
T he p ur p ose of t he E Val uati o n of t he Ne xt Ge nerati o n 
W A T C H M A N L A A Cl os ure 
Tec h n O L o g y i n 
N o n -Val v ular 
A F Pati E nts  ( E V O L V E) st u d y 
was t o e val uat e t he 
i m pla nta bilit y of t he Ge n 4 W A T C H M A N L A A Cl os ure De vice i n patie nts wit h n o n-val v ular 
atrial fi brillati o n ( A F) wit h a C H A D S 2 str o ke ris k stratificati o n of 1 or greater. T h e pri mar y 
o bjecti ves of t he st u d y were t o ass ess s uccessf ul deli ver y a n d rel ease of t he W A T C H M A N 
( Ge n 4) Cl os ure De vic e, t he occ urre nce of s eri o us pericar dial eff usi o ns a n d t he disc o nti n uati o n 
of warfari n at 4 5 d a ys. Patie nts w h o ha d n o n -val v ular par o x ys mal, p ersiste nt,  or per m a ne nt 
A F, h a d a C H A D S 2 sc ore of ≥1, a n d were eli gi ble f or warfari n t hera p y were s cree ne d as 
ca n di dates f or t he st u d y a n d i m pla nt.  
 
I n t he E V O L V E st u d y, t he s uccessf ul deli ver y a n d releas e of t he W A T C H M A N Ge n 4 Cl os ure 
De vice a n d t he occ urre n ce of seri o us pericar dial eff usi o ns were eit her c o nsiste nt wit h or a n 
i m pr o ve me nt u p o n t he res ults fr o m t he P R O T E C T A F st u d y. T heref ore, t he ac ute o bjecti ves 
of t he st u d y were m et a n d de m o nstrate peri car dial eff usi o n a n d de vice reca pt ure rates l o wer 
t ha n t hat see n wit h t he Ge n 2. 5 De vice i n P R O T E C T A F. T his de m o nstrates t hat t he Ge n 4 
W A T C H M A N L A A Cl os ure De vic e c o ul d be s afel y i m pla nte d i n patie nts  wit h n o n -val v ular 
atrial fi brillati o n ( A F) wit h C H A D S 2 str o ke ris k sc ore of 1 or greater. T he cl ose d distal e n d of 
t his ge nerati o n de vice was si milar t o W A T C H M A N F L X, h o we ver, f or b usi ness p ur p oses, t he 
c o m mercializ ati o n of t he Ge n 4 de vice was n ot p urs ue d i n lie u of d e vel o pi n g W A T C H M A N 
F L X . 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2 8  of 1 0 2  
  
 
T he R E gistr y o n W A T C H M A N O utc o mes i n Real -Life Utilizati o n ( E W O L U TI O N) st u d y was 
a n o bser vati o nal, pr os p ecti ve, si n gle -ar m, m ultice nter cli nical st u d y ( E ur o pe, Mi d dle E ast, 
R ussia) t hat c o m pile d  real-w orl d cli nical o ut c o me data f or 
W A T C H M A N L A A Cl os ure 
De vice i n a c o m mercial setti n g a n d c ollect e d  h ealt h care usa ge data f or rei m b urse me nt 
decisi o ns i n certai n c o u ntries; E W O L U TI O N c o nti n ues t o b uil d o n t he e xisti n g W A T C H M A N 
cli nical datab ase .  E W O L U TI O N is a p urel y o bs er vati o nal p ost -m ar ket d ata c ollecti o n st u d y. 
C o nsec uti ve e nr oll me nt was str o n gl y e nc o ura ge d, a n d ac hie ve d i n m ost sites, t o mi ni mize 
selecti o n bias a n d mai ntai n t he stre n gt hs of a lar ge-scal e, all-c o mers cli nical re gistr y. A t otal 
of 1 0 2 0 p atie nts sc h e d ule d f or a W A T C H M A N i m pla nt at 4 7 ce nters i n 1 3 c o u ntries were 
e nr olle d, a n d s u bj ects were  f oll o we d f or t w o years after W A T C H M A N i m pla ntati o n acc or di n g 
t o sta n dar d me dical practice. A nal yses i n cl u ded  pr oce d ural a n d l o n g -ter m data, i ncl u di n g 
str o ke/e m b olis m, blee di n g, a n d deat h. 2 1 -2 3 
 
B aseli ne/i m pla nt data, t he res ults of t he peri -pr oce d ural a n al yses, a n d dat a t hr o u g h t he first 
a n n ual visit  were prese nt e d f or t he 1 0 2 0 s u bjects  w h o u n der we nt  t he i m pla nt pr oce d ure.2 2 -2 3  
T he E W O L U TI O N p o p ulati o n was at hi g h ris k f or str o ke prese nti n g wit h C H A D S 2  ( 2. 8 ± 1. 3) 
a n d C H A 2D S 2-V A Sc ( 4. 5 ± 1. 6) sc ores. T he p o p ul ati o n ha d a  m o d erate -t o-hi g h ris k of blee di n g 
wit h a n a vera g e H A S -B L E D sc ore: 2. 3 ± 1. 2. A p pr o xi matel y 7 2 % of patie nts i n E W O L U TI O N 
were d ee me d u ns uita ble f or O A C b y t heir p h ysicia n. T he de vice w as s uccessf ull y de pl o ye d i n 
9 8. 5 % of patie nts wit h n o or mi ni mal resi d ual fl o w ac hie ve d i n 9 9. 8 % of i m pla nte d patie nts. 
T here were t we nt y -si x ( 2. 8 %, 1. 6– 3. 6 %) seri o us a d verse e ve nts occ urri n g i n 2 3 s u bjects 
re p orte d as relati n g t o t he pr oce d ure at 7 da ys.  Ei g htee n were c o nsi dere d Maj or Car diac E ve nts 
( 1. 8 %). T here was o ne case of deat h as a c o nse q u e nce of a n air e m b olis m d uri n g t he i m pla nt 
pr oce d ure. T hree a d diti o nal deat hs  wit hi n 7  da ys a p pear u nrelat e d t o t he de vice. T hes e rates of 
pr oce d ural s uccess a n d  7 -da y de vice -rel ate d S A Es were l o wer t ha n t h ose f o u n d i n P R O T E C T 
A F , C A P, P R E V AI L , a n d C A P 2.  
 
T he a n n ual rate of is c h e mic str o ke was 1. 3/ 1 0 0 pt. -years, w hi c h tra nslates i nt o a n 8 4 % ris k 
re d ucti o n, as c o m pare d wit h t he calc ulate d str o ke rate of 7. 2/ 1 0 0 pt. -years i n t he a bse nce of str o ke 
pre ve nti ve t h era p y f or si milar C H A 2D S 2-V A Sc  sc ores. T here 
were n o occ urre n ces of 
peri pr oce d ural str o k es a n d n o fat al str o kes i n t he st u d y. C o m bi ni n g isc he mic str o ke wit h TI A a n d 
s yste mic t hr o m b oe m b olis m, t he a n n ual rate is 2. 0/ 1 0 0 pt. -years, tra nslati n g i nt o a n 8 0 % ris k 
re d ucti o n as c o m pare d t o t he e x pecte d rate of 1 0. 1// 1 0 0 pt. -years b ase d o n C H A 2D S 2-V A Sc  
sc ores. Ma j or blee di n g ( w hic h i ncl u des fatal a n d life t hreate ni n g) ali g ns wit h t he L A A C-s pecific 
m o dificati o ns a n d refi n e me nts descri be d b y T zi kas et al . i n t he c o nse ns us d oc u me nt o n 
defi niti o ns, e n d p oi nts a n d data c ollecti o n re q uire me nts. I ntracra nial blee di n g a n d car di ac 
ta m p o na de are al w a ys c o nsi dere d maj or blee di n g wit h o ut f urt her assess me nt criteria. T he a n n ual 
rate of maj or blee di n g i n t he st u d y was 3. 3/ 1 0 0 pt. -years, w hic h c orres p o n ds t o a 3 4 % ris k 
re d ucti o n, as c o m pare d wit h t he rate of 5. 0// 1 0 0 pt. -years t ha t w o ul d b e e x pecte d u n der V K A 
t hera p y base d o n a c o m p ara ble H A S-B L E D sc ore. T he maj orit y of t he blee di n g e ve nts occ urre d 
o utsi de t he peri pr oce d ural peri o d. T he rate of maj or blee di n g e ve nts, e xcl u di n g pr oce d ural 
blee di n gs, is 2. 7/ 1 0 0 pt. -years, w hic h c orres p o n ds t o a 4 6 % re d ucti o n as c o m pare d wit h t he 
e x pecte d rate of 5. 0/ 1 0 0 pt. -years bas e d o n H A S -B L E D sc ore.  
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 2 9  of 1 0 2  
  
T he W A T C H M A N A Sia Pacific Re gistr y ( W A S P) is a n Asia/ Pacific re gistr y wit h i de ntical 
desi g n t o E W O L U TI O N t hat c o m piles real -w orl d cli nical o utc o me data f or t he W A T C H M A N 
L A A Cl os ure De vice i n a c o m mercial s etti n g a n d c ollects healt h care usa g e dat a f or 
rei m b urse me nt decisi o ns i n certai n c o u ntries. Li ke E W O L U TI O N, 
W A S P is a p urel y 
o bser vati o nal p ost -mar k et data c ollecti o n st u d y.  Res ults are i n li ne 
wit h t he lar ger 
E W O L U TI O N st u d y: s uccessf ul i m pla ntati o n occ urre d i n 9 8. 5 % of patie nts; 7 -da y 
de vice/ pr oce d ure -relate d S A E rate was 3. 0 %. After 2 years of f oll o w-u p t he rates of isc h e mic 
str o ke/ TI A/s yste mic e m b olis m a n d maj or blee di n g were 1. 9 a n d 2. 3  per 1 0 0 -P Y, res p ecti vel y, 
re pres e nti n g relati ve re d u cti o ns of 7 7 % a n d 4 9 % v ers us e x pecte d rates per ris k sc ores 2 4. 
 
 
T he W A T C H M A N N e w E nr ol me nt P ost -A p pr o val S ur veilla nce A nal ysis Pla n ( N E S Te d S A P) is 
desi g ne d t o assess l o n g -ter m safet y a n d effecti v e ness o utc o mes ass o ciat e d wit h t he use a n d 
i m pla ntati o n of t he W A T C H M A N Left Atrial A p pe n da ge ( L A A) Cl os ure T ec h n ol o g y i n a r o uti ne 
cli nical setti n g.  T his is a n a nal ysis pla n t hat will utilize data c ollect e d b y t he A C C F’s L A A O 
Re gistr y. All data a nal yse d will be fr o m patie nts recei vi n g a B ost o n Scie ntific C or p orati o n 
W A T C H M A N de vi ce at h os pitals partici pati n g i n t he L A A O Re gis tr y. As part of re g ulat or y 
re q uire me nts, t he W A T C H M A N N E S Te d S A P will c ollect de vice safet y a n d effecti ve n ess data 
o n 2, 0 0 0 patie nts e nr oll e d i n t he L A A O Re gistr y.  Si nce t he N E S Te d S A P le vera g es L A A O 
Re gistr y patie nt data, patie nt data ele me nts c ollecte d f or t he N E S Te d S A P will be i de ntical t o 
t h ose c ollecte d f or L A A O Re gistr y patie nts. 
 
T he pri mar y c o h ort dat a of 1 0 0 0 s u bjects ha v e  bee n  re p orte d.  C o m pare d wit h pre vi o us trials a n d 
re gistries ( Fi g ure), t he p atie nts were ol der a n d ha d hi g her baseli ne str o ke a n d blee di n g ris ks ( m ea n 
a ge 7 6. 5 ± 8. 1, C H A 2 D S 2 -V A Sc 5. 0 ± 1. 4, H A S -B L E D 2. 7 ± 1. 0, 3 8 % fe male). T he c o m p osite 
pri mar y safet y e n d p oi nt e ve n t rat e of 1. 4 9 % c o m pares fa v ora bl y t o t he rates o bser ve d i n pri or 
trials. T he u p per 9 5 % c o nfi de nce i nter val f or t he pri mar y safet y e n d p oi nt ( 2. 3 2 %) was bel o w t he 
pre -s pecifie d t hr es h ol d ( 3. 3 6 %). T h us, p r oced ural safet y res ults fr o m t h e U S N E S Te d P ost -
a p pr o val st u d y are c o nsiste nt wit h pri or cli nical st u dies i n a hi g her ris k p o p ulati o n. C o nti n ue d 
cli nical o utc o mes s ur veilla nce will g ui de L A A O as a n o pti o n f or hi g h -ris k patie nts wit h n o n -
val v ular atrial fi brillati o n w h o ha ve reas o ns t o see k a n alter nati ve t o oral a ntic oa g ulati o n 2 5. 
 
S A L U T E is a s t u d y t o e val uate t he S A fet y a n d effecti ve n ess of t he L eft atrial a p pe n d a ge 
cl os ure t hera p y f or p atie nts 
wit h n o n -val v U lar atrial fi brillati o n at i ncreas e d ris k of 
T hr o m b o E m b olis m .  T his st u d y was c o n d ucte d i n Ja pa n; e nr oll me nt a n d l o n g -ter m f oll o w-u p  
are c o m plete.  A t otal of 5 4 s u bjects (i ncl u di n g 1 2 R oll -i n) wit h N V A F w h o ha d a C H A 2 D S 2-
V A Sc sc ore ≥2 were e nr olle d. All 4 2 s u bjects i n t he i nte nti o n t o treat (I T T) c o h ort u n der we nt 
s uccessf ul i m pla ntati o n of t he L A A C d e vice wit h o ut a n y seri o us c o m plicati o ns, ac hie vi n g t he 
pres pecifi e d perf or ma n ce g oal. T he effecti ve L A A C rate was mai ntai ne d at 1 0 0 % fr o m 4 5 
da ys t o 1 2 m o nt hs p ost -i m pla nt, ac hie vi n g t he pres pecifie d perf or ma n ce g o al. D uri n g f oll o w-
u p, 1 s u bject die d of h eart fail ure, a n d 3 ha d isc he mic n o n -disa bli n g str o kes, b ut t here were n o 
cases of he m orr ha gic str o ke or s yste mic e m b olis m. T he fi nal res ults of t he S A L U T E trial 
de m o nstrate d t hat t he 
W A T C H M A N L A A C de vice is a n effecti ve a n d safe alter nati ve 
n o n p har mac ol o g ic al t hera p y f or str o ke ris k re d ucti o n i n Ja pa nese N V A F p atie nts w h o are n ot 
o pti mal ca n di dates f or lifel o n g a ntic oa g ulati o n 2 6 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 0  of 1 0 2  
  
 
T he  Assess me nt of t he W A T C H M A N T M  De vice i n Patie nts U ns uita ble f or Oral 
A ntic oa g ulati o n ( A S A P -T O O)  St u d y is desi g ne d  t o esta blis h t he safet y a n d effecti ve ness of 
t he W A T C H M A NT M  Left Atrial A p pe n da ge Cl os ure De vice, i ncl u di n g t he p ost -i m pla nt 
me dicati o n re gi me n, f or s u bjects wit h n o n -val v ular atrial fi brillati o n w h o are dee me d n ot t o 
be eli gi ble f or a ntic o a g ulati o n t hera p y t o re d u ce t h e ris k of str o ke. T h e de vi ce is i nte n de d t o 
re d uce t h e ris k of t hr o m b oe m b olic isc he mic str o ke a n d s yste mic e m b olis m .  E nr oll me nt 
starte d i n Fe br uar y 2 0 1 7 a n d was ter mi nat e d Oct o ber 1 5, 2 0 2 0 d ue t o sl o w e nr oll me nt wit h a 
t otal of 4 8 1 ra n d o mize d s u bjects. F oll o w u p is o n g oi n g. 
 
 
PI N N A C L E F L X is a pr os pecti ve, n o n -ra n d o mize d, m ulti-ce nter i n vesti gati o n t o esta blis h t he 
safet y a n d effic ac y of t he 
W A T C H M A N F L X L A A C De vice. T he trial has c o m plete d 
e nr oll me nt of t he 4 0 0 s u bjects re q uire d f or t he pri mar y a nal yses  a n d f oll o w -u p is c o m plete.  
T he me a n a g e was 7 3. 8 ± 8. 6 years a n d t he mea n C H A 2 D S 2 -V A Sc sc ore was 4. 2 ± 1. 5. T he 
i nci de nce of t he pri mar y safet y e n d p oi nt ( occ urre n ce of eit her deat h, isc he mic str o ke, s yste mic 
e m b olis m, or de vice - or pr oce d ure -relate d e ve nts re q uiri n g car diac s urger y wit hi n 7 da ys p ost -
pr oce d ure or b y h os pital disc har ge, w hic h e ver was later) was 0. 5 % wit h a o ne -si de d 9 5 % u p per 
c o nfi de nce i nter val ( CI) of 1. 6 %, meeti n g t he perf or ma nce g oal ( P G) of 4. 2 % ( P < 0. 0 0 0 1). T he 
i nci de nce of t he pri mar y effecti ve n ess e n d p oi nt (effecti ve L A A cl os ure ( peri-de vice fl o w ≤5 
m m) at 1 2 m o nt hs) was 1 0 0 %, wit h a o ne si de d 9 5 % l o wer CI of 9 9. 1 %, a g ai n meeti n g t he P G 
of 9 7. 0 % ( P < 0. 0 0 0 1). De vice -relat e d t hr o m b us was re p orte d i n 7 patie nts, n o patie nts 
e x perie n ce d pericar dial eff usi o n re q u iri n g o p e n car diac s ur ger y, a n d t here were n o de vice 
e m b olizati o ns. L A A cl os ure wit h t his ne xt g e nerati o n L A A cl os ur e de vice was ass oci ate d wit h 
a l o w i nci de nce of a d v ers e e ve nts a n d a hi g h i nci de nce of a nat o mic cl os ur e. 2 7 
 
F L Xi bilit y is a E ur o pea n pr os pecti ve, n o n -ra n d o mize d, m ulti-ce nter i n vesti gati o n desi g ne d t o 
c ollect real -w orl d cli nical o utc o me data f or patie nts w h o are i m pla nte d wit h t he W A T C H M A N 
F L X de vice i n a c o m mercial cli nical setti n g acc or di n g t o its la belli n g  ( p ost-mar ket, sta n dar d 
of care st u d y ). T he p ur p ose of F L Xi bilit y is t o pr o vi de a d diti o nal e vi de nce of t he safet y a n d 
perf or ma n ce of t h e de vi ce. T h e trial c o m plete d e nr oll me nt i n J ul y 2 0 2 0 a n d f oll o w -u p is 
o n g oi n g . 
I Ca n s E e Left Atrial A p pe n da ge (I C E L A A) Cli nical St u d y is a pr os pecti ve, n o n-
ra n d o mize d, si n gle-ar m, m ulti -ce nter i n vesti gati o n t o assess t he use of I C E t o g ui de 
W A T C H M A N F L X i m pla nts f or s u bjects wit h n o n -val v ular atri al fi brillati o n t o re d uce t he 
ris k of str o ke . A p pr o xi m atel y 1 0 0 s u bjects will be f oll o we d t hr o u g h t he e nr oll me nt peri o d, at 
de vice i m pla nt, t he n at i nter vals of 4 5 da ys. T h e pri mar y o bjecti ve of t his  st u d y is t o assess 
t he use of i ntracar diac ec h ocar di o gra p h y (I C E) i m a gi n g of t he Left Atrial A p pe n da ge 
d uri n g  W A T C H M A N F L X Left Atrial A p p e n da g e Cl os ure ( L A A C) i m pla nt pr oce d ure f or 
s u bjects wit h n o n-val v ular atrial fi brillati o n. T his st u d y has c o m plete d e nr oll me nt a n d f oll o w 
u p.  
 
T he C H A M PI O N st u d y is a pr os pecti ve, ra n d o mize d, m ulti-ce nter gl o bal i n vesti gati o n t o 
deter mi ne if left atrial a p pe n da ge cl os ure wit h t he W A T C H M A N F L X De vice is a 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 1  of 1 0 2  
  
reas o na bl e alter nati ve t o N O A Cs i n patie nts wit h n o n-val v ular atri al fi brillati o n.  A ma xi m u m 
of 3 0 0 0 s u bjects will be f oll o we d t hr o u g h t he e nr oll me nt peri o d, at de vice i m pla nt, t he n at 
i nter vals of 9 0 da ys, 1 2 0 da ys ( L A A i ma gi n g), 1 2 m o nt hs, 2 4 m o nt hs, 3 6 m o nt hs, 4 8 m o nt hs 
a n d 6 0 m o nt hs. T he pri mar y o bjecti ve of t his st u d y is t o deter mi ne if left atrial a p pe n da g e 
cl os ure wit h t he W A T C H M A N F L X de vice is a reas o na bl e alter nati ve t o n o n -vita mi n K oral 
a ntic oa g ula nts ( N O A Cs) i n patie nts wit h n o n -val v ular atrial  fi brillati o n. T his st u d y is 
c urre ntl y e nr olli n g.  
 
4. 3.  St u dy R ati o n ale  
L A A cl os ure wit h a W A T C H M A N De vice is c urre ntl y use d i n patie nts w h o are c o nsi d ere d 
p o or ca n di dates f or l o n g -ter m O A C; h o we ver, patie nts w h o u n der g o A F cat heter a blati o n 
pr oce d ures a n d are at ris k f or str o ke are n ot necessaril y dee me d p o or ca n di dates f or O A C 
u nless ot her fact ors e xist  (i.e., fact ors u nrelat e d t o t he A F cat heter a blati o n pr oce d ure). 
O P TI O N  is desi g ne d t o d eter mi ne if left atrial a p pe n da ge cl os ure wit h t he W A T C H M A N 
F L X D e vice is a reas o n a ble alter nati ve t o or al a ntic oa g ulati o n f oll o wi n g perc u ta ne o us 
cat heter a blati o n f or n o n -val v ular atrial fi brillati o n . 
5.  De vice Descri pti o n  
T he W A T C H M A N F L X Deli ver y S yste m c o nsists of t he Deli ver y Cat h eter a n d t he pre -l oa de d 
Cl os ure De vice,  Fi g ure 1 . T he W A T C H M A N F L X Deli ver y S yste m is use d i n c o nj u ncti o n 
wit h a 
W A T C H M A N Access S yste m. T o get her, t he W A T C H M A N 
Access S yste m a n d 
W A T C H M A N F L X Deli ver y S yste m per mit de vice place me nt i n t he L A A via fe m oral ve n o us 
access a n d cr ossi n g t he i nter -atrial s e pt u m i nt o t he left atri u m.  T h e W A T C H M A N Access 
S yste m is c o m merciall y a vaila ble  a n d a re q uir e d access or y f or use wit h t he W A T C H M A N 
F L X pr oce d ures.   T he W A T C H M A N Tr u Seal Access S yste m is c o m merciall y a vaila bl e  i n 
select ge o gra p hi es a n d is c o m pati ble wit h t he 
W A T C H M A N F L X Deli ver y S yste m.   If 
a d diti o nal ge nerati o ns of t he W A T C H M A N Access S yste ms bec o me  c o m merciall y a v aila ble 
d uri n g t he e nr oll me nt p h ase of t he st u d y, t hese Access S yste ms ma y  be use d i n O P TI O N .  
 
5. 1. 1.  W A T C H M A N F L X Delivery Syste m a n d wit h Pre -l o a de d L A A C Device 
T he Deli ver y Cat heter f or W A T C H M A N F L X c o nsists of a n i n ner c ore wire wit h a rei nf orce d 
brai de d jac k et t hat is c o n necte d t o t he de pl o y me nt k n o b at t he pr o xi mal e n d a n d a scre w t hr ea d 
asse m bl y at t he distal e n d. T he o uter s heat h has a n o verall pr ofile of 1 2 F.  
 
T he W A T C H M A N F L X  D e vice is pre-l oa de d i nt o a Deli ver y Cat heter a n d is de pl o ye d b y 
l o ose ni n g t he val v e o n t he Deli ver y S yste m a n d retracti n g t he o uter s heat h. T he W A T C H M A N 
F L X D e vice ca n b e partiall y reca pt ur e d a n d re de pl o ye d if t he de vi ce is t o o distal. If t he Cl os ure 
D e vice is de pl o ye d t o o pr o xi mal, it ca n b e f ull y reca pt ure d.  T he W A T C H M A N F L X D e vice 
has t he a d d e d a bilit y o ver t he e xisti n g W A T C H M A N ( Ge n 2. 5) d e vice t o b e re d e pl o ye d after 
bei n g f ull y reca pt ure d. As wit h t he e xisti n g W A T C H M A N De vice, t he Cl os ure D e vice is 
releas e d b y r otati n g t he d e vice de pl o y me nt k n ob c o u nter cl oc k wise.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 2  of 1 0 2  
  
 
T he W A T C H M A N F L X De vice is c o m prise d of a self -e x pa n di n g niti n ol fra me str uct ure wit h 
fi xati o n a nc h ors ar o u n d t he Cl os ure D e vice peri meter a n d a per m ea ble p ol yester fa bric t hat 
c o vers t he atrial faci n g s urface of t he Cl os ure D e vi ce. T he Cl os ure D e vice is c o nstrai ne d wit hi n 
t he Deli ver y Cat heter u ntil de pl o y me nt i n t he L A A. T he 
W A T C H M A N F L X De vice is 
a vaila ble i n 5 sizes , fr o m 2 0 t o 3 5 m m. It is si milar t o t he c urre ntl y a vaila ble W A T C H M A N 
(G e n 2. 5) D e vice, b ut c o vers a sli g htl y lar ger ra n ge  of a p pe n d a ge osti u m dia meters,  fr o m 1 4  
t o 31. 5  m m.  A p pr o priate Cl os ure  De vice sizi n g is deter mi ne d b y L A A m eas ure m e nts usi n g 
fl u or osc o p y (fl u or o) a n d ec h ocar di o gra p hi c g ui da nce . 
 
Fi g ure 1 : W A T C H M A N Deli ver y S yste m ( Deli ver y C at heter & L A A Cl os ure De vice)  
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 3  of 1 0 2  
  
 
 
Si milar t o t he pre vi o us W A T C H M A N De vices, t he W A T C H M A N F L X De vice is desi g ne d t o 
be per ma ne ntl y i m pla nte d at or sli g htl y distal t o t he osti u m ( o pe ni n g) of t he L A A t o tra p 
p ote ntial e m b oli bef ore t he y e xit t he L A A. T he pl ace me nt pr oce d ure ca n b e d o ne u n der l o cal 
or ge neral a nest hesi a i n a cat heteri z ati o n la b orat or y.  
 
I n a d diti o n, W A T C H M A N F L X i nc or p orat es t he f oll o wi n g n o vel feat ures t o e n ha nce t he user 
e x perie n ce f or t he 
W A T C H M A N L A A Cl os ur e Tec h n ol o g y c o m p are d t o t he e xisti n g 
W A T C H M A N Cl os ure De vice wit h D eli ver y S yste m:  
•  Cl ose d Distal E n d –  Pr o vi des i m pr o ve d de pl o y me nt sta bilit y a n d c o ntr ol, wit h 
atra u matic distal str uct ur e . 
•  F ull y Reca pt ura ble a n d Re de pl o ya ble –  Desi g ne d t o d ecrease t he n u m ber of de vices 
use d a n d s heat h e xc ha n ges per case, 
w hic h 
ma y re d uce pr oce d ure ti me a n d 
c o m plicati o ns ass ociate d wit h s heat h e xc ha n g e.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 4  of 1 0 2  
  
•  Decrease d Reca pt ur e F orce –  Desi g ne d t o i m pr o ve user e x p erie n ce.  
•  I n crease d C o nf or m a bilit y –  Desi g ne d t o c reate b etter left atri al a p pe n d a g e seal d ue t o 
t he i ncreas e d n u m ber of c o ntact p oi nts ar o u n d t he L A A osti u m, desi g ne d t o pr o m ote 
s h ort-ter m heali n g. 
•  Decrease d E x p ose d 
Met al V ol u me o n Pr o xi mal Face –  M a y pr o m ote s h ort-ter m 
heali n g.  
•  E n ha nce d Ra di o p acit y –  Desi g ne d t o i m pr o ve visi bilit y u n der fl u or osc o p y.  
•  S maller a n d Lar ger De vi ce Size  –  Desi g ne d t o a ll o w f or tr eat me nt of c o m ple x, s hall o w 
L A A a n at o mies. 
•  Greater O v erla p i n De vi ce Sizi n g C h oices  –  Desi g ne d t o all o w f or treat me nt of a wi der 
ra n ge of a p pe n d a ge sizes. 
 
5. 1. 2.  W A T C H M A N Access Syste m a n d W A T C H M A N Tr u Se al Access Syste m ( Access 
S he at h a n d Dil at or)  
T he 1 4 F ( 1 2 F I D) tr a nsse ptal Access S heat h f or b ot h t he W A T C H M A N Access S yste m a n d 
W A T C H M A N Tr u Seal Access S yste m is utilize d t o gai n access t o t he L A A a n d ser ves as a 
c o n d uit f or t he W A T C H M A N F L X Deli ver y S yste m. T he distal e n d of t h e Access S heat h is 
a vaila ble i n t hr ee c ur ve st yles t o assist wit h place m e nt of t he s h eat h i nt o t he L A A.  T he vari o us 
c ur ve st yles all o w f or c o a xial place me nt of t he s h eat h i nt o t he L A A. T he distal ti p c o ntai ns a 
mar ker ba n d f or i n sit u vis ualizati o n as well as sizi n g mar ker ba n ds use d t o ga u ge if t he Access 
S heat h is p ositi o ne d at t he a p pr o pri ate de pt h i n t he L A A base d o n t he de vice size selecte d.  
 
T he Access S heat h a n d Dilat or are utilize d t o g ai n access t o t he L A A after i nitial tra nsse ptal 
access i nt o t he left atri u m has bee n esta blis he d. O nce t he Access S heat h is p ositi o ne d i nt o t he 
left atri u m a n d t he Dilat or has bee n re m o ve d, t he Access S heat h t he n s er ves as a c o n d uit f or 
t he Deli ver y S yste m. T he Deli ver y S yste m is i ntr o d uce d i nt o t he Access S heat h a n d t he 
c o m p o ne nts s na p t o get her t o act as o ne d uri n g de vice i m pla ntati o n.  
 
W A T C H M A N Tr u Seal Access S yste m , w hic h uses a n i de ntical dilat or t o t he W A T C H M A N 
Access S yste m,  is a n e n h a nce d n e xt-ge n erati o n Access S yste m t o re place t he e xisti n g matri x 
of t he 
W A T C H M A N Access S yste m.  T he 
W A T C H M A N Tr u Seal Access S yste m is 
c o m pati ble wit h all c o m merciall y a v aila ble W A T C H M A N Left Atrial A p pe n da ge Cl os ure 
De vices wit h D eli ver y S yste ms.  
 
I n v esti gat ors sh o ul d h a v e e x p erie nce usi n g  t h e 
W A T C H M A N F L X De vice a n d Tr u Seal 
Access S yste m, pri or t o utilizi n g t he m t o get her i n t he trial.   
 
 

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 5  of 1 0 2  
  
 
 
Fi g ure 3 : W A T C H M A N Tr u Se al Access S yste m 
 
 
 
Fi g ure 2 : W A T C H M A N Access S yste m 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 6  of 1 0 2  
  
 
5. 1. 3.  I n dic ati o ns f or Use 
T he pla n ne d i n dicati o n f or use wit hi n t he O P TI O N st u d y is as f oll o ws:  
T he W A T C H M A N a n d W A T C H M A N F L X De vice are i n dicate d t o re d uce t he ris k of 
t hr o m b oe m b olis m fr o m t he left atrial a p p e n da g e i n s u bjects wit h n o n -val v ular atrial 
fi brillati o n w h o: 
•  Are at i ncreas e d ris k f or str o ke a n d s yste mic e m b olis m base d o n C H A 2D S 2-V A Sc 
sc ores f oll o wi n g c at heter a blati o n of atrial fi brillati o n; a n d 
•  A re dee me d s uita ble  f or a ntic oa g ulati o n t hera p y 
 
N ote: I n c o u ntries w h ere C E mar k  a p plies, t he O P TI O N i n dicati o n is wit hi n t he C E mar k  
a p pr o ve d I n di cati o n f or Use.  
6.  St u d y O bjecti ve  
T he pri mar y o bje cti ve of t his st u d y is t o deter mi ne if left atrial a p pe n da ge cl os ure wit h t he 
W A T C H M A N F L X D e vice is a reas o na ble alter nati ve t o oral a ntic oa g ul ati o n f oll o wi n g 
perc uta n e o us cat h eter a bl ati o n f or n o n -val v ular atrial fi brillati o n.  
7.  St u d y E n d p oi nts  
7. 1.  Pri m ary Effective ness E n d p oi nt  
W A T C H M A N t hera p y is n o n -i nferi or f or t he occ urre nce of str o ke (i ncl u di n g isc he mic 
a n d/ or he m orr h a gic), all ca use deat h, a n d s yste mi c e m b olis m at 3 6 m o nt hs.   T his e n d p oi nt is 
defi ne d as t he Ka pla n M eier esti mate of ti me t o first occ urre nce of str o ke (i ncl u di n g isc he mic 
a n d/ or he m orr h a gic), all ca use deat h, or  s yste mic e m b olis m at 3 6 m o nt hs. 
7. 2.  Pri m ary S afety E n d p oi nt  
W A T C H M A N t hera p y is s u peri or f or n o n -pr oce d ural blee di n g t hr o u g h 3 6 m o nt hs (I S T H 
maj or blee di n g a n d cli nic all y rele va nt n o n -m aj or blee di n g) . T his e n d p oi nt is defi ne d as the 
Ka pla n  Meier esti mate of ti me t o first occ urre n ce of n o n -pr oce d ural I S T H maj or blee di n g or  
cli nicall y rele va nt n o n -m aj or blee di n g  t hr o u g h 3 6 -m o nt hs . 
7. 3.  Sec o n d ary  E n d p oi nt  
W A T C H M A N t hera p y is n o n -inferi or  f or I S T H maj or blee di n g at 3 6 m o nt hs (i ncl u di n g 
pr oce d ural blee di n g) . T his e n d p oi nt is defi ne d as t he  Ka pla n Mei er esti mat e s of ti me t o first 
occ urre nce  of maj or ble e di n g at 3 6 m o nt hs . 
7. 4.  A d diti o n al A n alyses  
1.  T he occ urre n ce a n d i n ci de nce of:  

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 7  of 1 0 2  
  
•  Str o ke  
o  Is c he mic str o ke 
o  He m orr ha gi c str o ke  
o  Disa bli n g str o ke  
o  N o n -disa bli n g str o ke  
•  S yste mic e m b olis m  
•  Pr oce d ural a n d n o n -pr oce d ural blee di n g  a n d classificati o ns; I S T H  maj or bl ee di n g a n d 
cli nicall y rele va nt n o n-m aj or blee di n g  
•  All -ca use d eat h  
o  Car di o vasc ular/ u n k n o w n deat h  
o  N o n -car di o vasc ular deat h  
•  De vice relate d T hr o m b us  
2.  De vice  s uccess (De vic e de pl o ye d a n d i m pla nte d i n c orrect p ositi o n ) 
3.  Rate s of effecti ve  ( defi ne d as jet size of ≤5 m m) a n d c o m plete ( defi ne d as n o peri -de vice 
fl o w) L A A cl os ure at 3 - a n d 1 2-m o nt hs  p ost i m pla nt  
4.  Free d o m fr o m A F  (see secti o n 1 3 f or defi niti o n)  
5.  Healt hcare res o urce utilizati o n  
6.  Q ualit y of life  
8.  St u d y Desi g n  
T his st u d y is a pr os pecti ve, ra n d o mize d, m ulti -ce nter, gl o bal i n vesti gati o n t o deter mi ne if left 
atrial a p pe n d a ge cl os ur e wit h t he W A T C H M A N F L X De vice is a reas o n a ble alter nati ve t o 
oral a ntic oa g ulati o n i n patie nts after perc uta ne o us a blati o n  of n o n -val v ular A F . 
 
I m pla nti n g in vesti gat ors will i ncl u de p h ysicia ns w h o ha ve W A T C H M A N ( Ge n 2. 5) a n d / or 
W A T C H M A N F L X i m pla nt e x perie n ce.  T h e W A T C H M A N F L X i m pla nti n g i n vesti gat or 
d oes n ot ha ve t o be t he s a me p h ysicia n  perf or mi n g a blati o n wit hi n t he trial.   All i m pla nti n g 
p h ysicia ns m ust ha ve c o m plete d W A T C H M A N F L X i m pla nt trai ni n g.  All  sites wit h o ut 
W A T C H M A N F L X e x p erie nce (i.e., h a ve i m pla nte d >  2 W A T C H M A N F L X de vices 
c o m merciall y or wit hi n t he PI N N A C L E F L X I D E) will be re q uire d t o i m pl a nt t w o R oll-i n 
s u bjects pri or t o i m planti n g i n t he mai n c o h ort of s u bjects.  R oll -i n s u bjects will be declare d 
pri or t o i m pla nt, m ust be c o m plete d pri or t o i m pla nti n g i n t he mai n ra n d o mize d c o h ort, a n d 
m ust meet all pr ot oc ol re q uire me nts .   
 
Sites will be li mite d t o t w o W A T C H M A N F L X i m pla nti n g i n vesti gat ors per i nstit uti o n i n 
ge o gra p hies w h ere t he de vice is i n vesti gati o nal.  
 
N ote: W hile t he de vic e is c o nsi dere d i n vesti gati o n al i n t he U nite d States, s ites w h o 
partici pate d i n t he PI N N A C L E F L X trial  a n d w h o ha d  t w o trai ne d W A T C H M A N F L X 
i m pla nti n g p h ysicia ns i n t hat st u d y ma y a d d o ne a d diti o nal i m pla nti n g p h ysicia n  f or t he 
O P TI O N st u d y . 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 8  of 1 0 2  
  
P erc uta ne o us  cat heter a bl ati o n usi n g c urre ntl y a vaila ble n o n -s ur gical sta n d ar d tec h ni q ues a n d 
mar ket -a p pr o ve d te c h n ol o g y  ma y  be perf or me d at t he ti me of t he W A T C H M A N  F L X  
i m pla nt pr oce d ure o nl y f or C o nc o mit a nt  A bl ati o n s u bjects   
 
•  T he pr oce d ures m ust occ ur o n t he sa me da y wit h t he a blati o n occ urri n g pri or t o t he 
W A T C H M A N F L X i m pla nt . 
•  C at heter a blati o n of t he L A A, n o n -sta n dar d a blati o n tec h ni q ues (e. g., C F A Es  a n d 
h y bri d a blati o n ) a n d a n y n o n -A F -relate d a blati o n (e. g., V T) are n ot per mitte d . 
•  Ot her c o nc o mita nt pr o ce d ures are  als o n ot per mitte d, i ncl u di n g, b ut n ot li mite d t o, 
tra nsc uta ne o us v al ve pr o ce d ures, p ace ma ker,  or I C D ge nerat or c ha n g e, etc . 
 
N ote: Se q ue ntial  A blati o n  s u bjects w h o nee d a re peat a blati o n ca n n ot c o m bi ne it wit h t he 
W A T C H M A N F L X i m pla nt pr oce d ure.  
F or all patie nts, C TI a bl ati o n a n d car di o versi o n ma y be perf or me d d uri n g a blati o n . 
8. 1.  Sc ale a n d D ur ati o n  
A ma xi m u m of 1 6 0 0  s u bjects will be ra n d o mize d i n t he st u d y at a ma xi m u m of 1 5 0 gl o bal 
sites.  A ma xi m u m of 2 6 0 a d diti o nal patie nts will be treate d i n t he r oll -i n p hase of t he st u d y. 
 
T he d urati o n of t he st u d y is e x pecte d t o last a p pr o xi matel y 6 4  m o nt hs. T he d urati o n of 
i n di vi d ual s u bject partici pati o n is e x pecte d t o last a p pr o xi matel y 3 6 m o nt hs b ut ma y var y per 
s u bject.  
 
Gi ve n t he n u m ber of sites t hat ha ve PI N N A C L E F L X e x p erie n ce, a n d t h e t otal n u m ber of 
pla n ne d sites, it is e x pect e d t hat t he n u m ber of r oll -i ns i n t he U nite d States will be 
a p pr o xi matel y 1 3 0.  
8. 2.  Tre at me nt Assi g n me nt  
A s u bject w h o si g ns i nf or me d c o nse nt is c o nsi dere d e nr olle d i n t he st u d y.  S u bjects will be 
ra n d o mize d t o O A C or W A T C H M A N F L X i n e q ual pr o p orti o n .  Ra n d o mizati o n will be 
stratifie d b y se q ue ntial vs. c o nc o mita nt pla n ne d a blati o n +/- W A T C H M A N i m pla ntati o n, t o 
hel p e ns ure b ala nce of treat me nt assi g n me nts wit hi n t he se q ue ntial a n d c o nc o mita nt gr o u ps.  
T he pla n ne d a bl ati o n pr o ce d ure t y p e, c o nc o mita nt or se q ue ntial, m ust be s p ecifie d pri or t o 
ra n d o mizi n g t he s u bject. 
8. 2. 1.  De vice Gr o u p Tre at me nt  
S u bjects ra n d o mize d t o t he de vice gr o u p will be i m pla nte d wit h t he W A T C H M A N F L X 
de vice.  W A T C H M A N F L X is a vaila ble i n 2 0, 2 4, 2 7, 3 1, a n d 3 5 m m m o dels t o fit left atrial 
a p pe n da g e ostia wi dt hs ra n gi n g fr o m 1 4. 0 - 3 1. 5 m m.  
 
After t he W A T C H M A N F L X i m pla nt, De vice Gr o u p s u bjects will be pres cri be d mar k et -
a p pr o ve d O A C a n d as piri n ( 7 5 -1 0 0 m g rec o m me n de d) u ntil t he 3 -m o nt h visit  f oll o we d b y 
as piri n u ntil  at least t he 1 2 -m o nt h visit  (rec o m me n de d f or d urati o n of t he tri al). 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 3 9  of 1 0 2  
  
8. 2. 2.  C o ntr ol Gr o u p Tre at me nt  
F oll o wi n g ra n d o mizati o n, c o ntr ol s u bjects m ust  c o nti n ue or start mar ket a p pr o ve d  O A C use d 
per I F U f or atrial fi brillati o n str o ke pre ve nti o n  a n d s h o ul d re mai n o n it  f or t he d urati o n of t he 
trial. 
 
Fi g ure 4 : St u d y Fl o w Di a gr a m 
  
 
N ot e: f or R oll -i ns s u bj ects wi n d o ws ar e c alc ul at e d fr o m i m pl a nt d at e, i nst e a d of r a n d o miz ati o n d at e 
8. 3.  J ustific ati o n f or t he St u dy Desi g n  
Patie nts u n der g oi n g A F a blati o n are n ot o nl y see ki n g s y m pt o m relief fr o m t he arr h yt h mia , 
b ut als o p urs ui n g str o ke pre ve nti o n.  A blati o n  al o ne has n ot bee n pr o ve n i n ra n d o mize d 
cli nical trials t o pre ve nt str o ke , a n d c urre nt s oci etal g ui deli nes rec o m me n d f or patie nts wit h a 
C H A 2D S 2-V A S c of 2 or greater t o c o nti n ue t heir oral a ntic oa g ulati o n i n defi nitel y1 8.  
Rece ntl y, L A A C has bee n s h o w n  t o be si milar t o O A C i n s u bjects wit h C H A2D S 2-V A S c >  2 
a n d a rati o nal e t o see k a n alter nati ve t o O A C.  T his st u d y  is desi g ne d t o deter mi ne if left 
atrial a p pe n d a ge cl os ur e wit h t he W A T C H M A N F L X De vice is a reas o n a ble alter nati ve t o 
oral a ntic oa g ulati o n f oll o wi n g perc uta ne o us cat h eter a blati o n f or n o n -val v ular atrial 
fi brillati o n. 
9.  S u bject Selecti o n  
9. 1.  St u dy  P o p ul ati o n a n d Eli gi bility   
 St u d y i ncl usi o n a n d e xcl usi o n criteria are i ncl u de d bel o w i n secti o ns 9. 2 a n d 9. 3.  

C o nfi de ntial  
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Pa ge 4 0  of 1 0 2  
  
9. 2.  I ncl usi o n Criteri a 
S u bjects w h o meet all of t he f oll o wi n g criteria  (see Ta ble 9. 2 -1 ) ma y be gi ve n c o nsi derati o n 
f or i ncl usi o n i n t his cli nical i n vesti gati o n, pr o vi de d n o e xcl usi o n criteri o n (see Secti o n 9. 3  
a n d Secti o n 9. 4 ) is met.  
T a ble 9. 2 -1 : I ncl usi o n Criteri a 
I ncl usi o n 
Criteri a  
1.  T he s u bject is of le gal a g e t o partici pate i n t he st u d y per t he la ws of t heir 
res pecti ve g e o gra p h y.  
2.  U n der we nt a pri or cat het er a blati o n pr o ce d ure f or n o n -val v ular A F bet w ee n 
9 0 a n d 1 8 0 da ys pri or t o ra n d o mizati o n (se q u e ntial) or is pla n ni n g t o ha ve 
cli nicall y i n dicate d cat h eter a blati o n wit hi n 1 0 da ys of ra n d o mizati o n 
(c o nc o mita nt). 
3.  T he s u bject has a calc ul ate d C H A 2 D S 2 -V A Sc sc ore of 2 or great er f or 
males or 3 or greater f or fe males.  
4.  T he s u bject is dee me d b y t he treati n g p h ysicia n t o be s uita ble f or t he 
pr ot oc ol defi ne d p h ar mac ol o gic re gi me n s. 
5.  T he s u bject is a ble t o u n der g o T E E e x a mi nati o ns.  
6.  T he s u bject or le g al re prese ntati ve is a ble t o u n dersta n d a n d is willi n g t o 
pr o vi de writte n i nf or me d c o nse nt t o partici pate i n t he trial.  
7.  T he s u bject is a ble a n d willi n g t o ret ur n f or re q uir e d f oll o w -u p visits a n d 
e xa mi nati o ns.  
9. 3.  E xcl usi o n Criteri a  
S u bjects w h o meet a n y o ne of t he f oll o wi n g e x cl usi o n criteria (T a ble 9. 3 -1 ) will be e xcl u de d 
fr o m t his cli nical st u d y. 

C o nfi de ntial  
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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 1  of 1 0 2  
  
T a ble 9. 3 -1 : E xcl usi o n Criteri a 
E xcl usi o n 
Criteri a  
1.  T he s u bject is c urre ntl y e nr olle d i n a n ot her i n vesti gati o nal st u d y t hat w o ul d 
directl y i nterfere wit h t he c urre nt st u d y, e xce pt w he n t he s u bject is partici pati n g 
i n a ma n dat or y g o ver n me ntal re gistr y, or a p urel y o bser vati o nal re gistr y wit h 
n o ass ociate d tr eat me nts. Eac h i nsta nce m ust be br o u g ht t o t he atte nti o n of t he 
s p o ns or t o deter mi ne eli gi bilit y, re gar dless of t y pe of c o-e nr oll me nt bei n g 
pr o p ose d.  
2.  T he s u bject re q uires l o n g -ter m a ntic oa g ulati o n t hera p y f or reas o ns ot her t ha n 
A F -relate d str o ke ris k re d ucti o n, f or e xa m ple d ue t o a n u n derl yi n g 
h y perc oa g ula ble state (i.e., e ve n if t he de vice is i m pla nte d, t he s u bjects w o ul d 
n ot be eli gi ble t o disc o nti n ue  O A C d ue t o ot her me dical c o n diti o ns re q uiri n g 
c hr o nic O A C t hera p y).  
3.  T he s u bject is dee me d b y t he treati n g p h ysicia n t o be u ns uita ble f or c hr o nic 
antic oa g ulati o n a n d/ or as piri n t hera p y  d ue t o blee di n g ris k, aller g y, or ot her 
reas o ns.  
4.  T he s u bject ha d or is pla n ni n g t o ha ve a n y car diac or maj or n o n -car diac 
i nter ve nti o nal or s ur gical pr oce d ure (e xcl u di n g n o n-val v ular A F a blati o n  a n d 
car di o versi o n ) wit hi n 3 0 da ys pri or t o or 6 0 da ys after ra n d o mizati o n 
[i ncl u di n g, b ut n ot li mite d t o: perc uta ne o us c or o nar y i nter ve nti o n (P CI), ot her 
car diac a blati o n ( V T a blati o n, etc.), etc.].  
5.  T he s u bject ha d a str o ke or tra nsie nt isc he mic attac k ( TI A) wit hi n t he 6 0 da ys 
pri or t o ra n d o mizati o n.  
6.  T he s u bject ha d a pri or maj or blee di n g e ve nt per I S T H defi niti o n wit hi n t he 1 4 
da ys pri or t o ra n d o mizati o n. Lac k of res ol uti o n of relate d cli nical se q uelae or 
pla n ne d a n d pe n di n g i nter ve nti o ns t o res ol ve blee di n g/ blee di n g s o urce, are a 
f urt her e xcl usi o n re gar dless of ti mi n g of t he blee di n g e ve nt. 
7.  T he s u bject has ha d a m y ocar dial i nfarcti o n ( MI) d oc u me nte d i n t he cli nical 
rec or d as eit her a n o n-S T ele vati o n MI ( N S T E MI) or as a n S T -ele vati o n MI 
( S T E MI), wit h or wit h o ut i nter ve nti o n, wit hi n 9 0 da ys pri or t o ra n d o mizati o n.  
8.  T he s u bject has a hist or y of atrial se ptal re pair or has a n A S D/ P F O de vice.  
9.  T he s u bject has a n i m pla nte d mec ha nical val ve pr ost hesis i n a n y p ositi o n.  
1 0.  T he s u bject is of c hil d beari n g p ote ntial a n d is, or pla ns t o bec o me pre g na nt 
d uri n g t he ti me of t he st u d y ( met h o d of assess me nt u p o n st u d y p h ysicia n’s 
discreti o n)  
1 1.  T he s u bject has a d oc u me nte d life e x pecta nc y of less t ha n t w o years.  
1 2.  T he s u bject has a car diac t u m or.  
1 3.  T he s u bject has si g ns/s y m pt o ms of ac ute or c hr o nic pericar ditis.  
1 4.  T here is e vi de nce of ta m p o na de p h ysi ol o g y.  
1 5.  T he s u bject has c o ntrai n dicati o ns (a nat o mical or me dical) t o perc uta ne o us 
cat heterizati o n pr oce d ures . 
1 6.  T he s u bject has d oc u me nte d N Y H A Class I V heart fail ure . 
1 7.  T he s u bject has d oc u me nte d s ur gical cl os ure of t he left atrial a p pe n da ge.  
1 8.  T he s u bject has a n acti ve i nfecti o n.  
 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 2  of 1 0 2  
  
9. 4.  Tr a nst h or acic Ec h oc ar di o gr a p hic  E xcl usi o n Criteri a  
After si g nat ur e of t he i nf or me d c o nse nt a n d pri or t o ra n d o mizati o n all e nr olle d s u bjects will 
u n der g o a tr a nst h oraci c ec h ocar di o gra p hic e val uati o n t o f urt her c o nfir m eli gi bilit y. S u bjects 
w h o meet a n y o ne of t he f oll o wi n g ec h o e xcl usi o n criteria ( Ta ble 9. 4 -1 ) will be e xcl u de d 
fr o m t his cli nical st u d y a n d m ust  n ot be ra n d o mize d .  T he  bas eli ne  T T E will  be d o ne t o 
e val uate all e xcl usi o n criteria  t o c o nfir m s u bject eli gi bilit y.  Criteria  o btai ne d fr o m car diac 
i ma gi n g perf or me d wit hi n 1 8 0 da ys  pri or t o ra n d o mizati o n ma y be use d  if all t he e xcl usi o n 
criteria ca n be e val uate d .  If all e xcl usi o n criteria were n ot o btai ne d o n t h e pri or car di ac 
i ma gi n g, a T T E will ha ve t o be c o n d uct e d at baseli ne. If a si g nifica nt car di ac e v e nt occ urs 
after t he car di ac i ma gi n g  w hic h ca u ses a c h a n ge i n car diac stat us [i.e., maj or C o n gesti ve 
Heart Fail ure ( C H F)  dec o m pe nsati o n]  t he baseli n e  T T E m ust  be re p eate d after i nf or me d 
c o nse nt a n d pri or t o ra n d o mizati o n. 
T a ble 9. 4 -1 : Tr a nst h or acic Ec h o E xcl usi o n Criteri a  
Tr a nst h or a cic 
Ec h o 
E xcl usi o n 
Criteri a  
1.  T he s u bject has L V E F < 3 0 %  
2.  T he s u bject has a n e xisti n g pericar dial eff usi o n wit h a circ u mfere ntial 
ec h o -free s pace > 5 m m.  
3.  T he s u bject has a hi g h - ris k pate nt f ora me n o vale ( P F O) wit h a n atrial 
se ptal a ne ur ys m e xc ursi o n > 1 5 m m or le n gt h > 1 5 m m.  
4.  T he s u bject has a hi g h -ris k P F O wit h a lar ge s h u nt defi ne d as earl y, wit hi n 
3 beats a n d/ or s u bsta ntial passa ge of b u b bles.   
5.  T he s u bject has si g nifica nt mitral val ve ste n osis (i.e., M V area < 1. 5 c m
2). 
1 0.  S u bject Acc o u nt a bilit y  
1 0. 1.  P oi nt of E nr oll me nt  
T he p oi nt of e nr oll me nt is t he ti me at w hic h a s u bj ect si g ns  a n d dates t he i nf or me d c o nse nt 
f or m (I C F).  N o st u d y s p ecific tests, pr o ce d ures, etc. ca n ta ke place u ntil t h e I C F is si g ne d.  
S u bjects t hat are det er mi ne d t o n ot meet cli nical or ec h o eli gi bilit y criteria after si g ni n g 
c o nse nt , a n d pri or t o r a n d o mizati o n, will be c o nsi dere d scree ni n g fail ures a n d will n ot c o u nt 
t o war ds t he e nr oll me nt ceili n g.  
 
S u bjects ma y be re -e nr olle d at a f ut ur e date u n der a ne w s u bject I D if it is deter mi ne d t hat t he 
reas o n t he s u bject scree n faile d n o l o n ger a p plies. 
1 0. 2.  S u bject St at us a n d Cl assific ati o n  
1 0. 2. 1.  Scree n F ail ure  
A s u bject w h o has a v ali d a n d si g ne d  i nf or me d c o nse nt b ut  is n ot ra n d o mize d is c o nsi dere d a 
scree n fail ure.  Scr ee n f ail ure s u bjects d o n ot c o u nt t o w ar ds t he e nr oll me nt ceili n g a n d will 
n ot be use d f or t he pri m ary a n alys es. Scree n fail ure  s u bjects s h o ul d be e xite d i m me diatel y 
u p o n deter mi ni n g t heir i neli gi bilit y. T he ori gi nal si g ne d inf or me d co ns e nt m ust be 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 3  of 1 0 2  
  
mai ntai ne d i n t he site’s s u bject file a n d t he f oll o wi n g f or ms m ust be c o m plete d  f or all 
i nf or mati o n c ollecte d pri or t o deter mi ni n g t he s u bject’s i neli gi bilit y: 
•  Baseli ne f or ms s uc h as, b ut n ot li mite d t o: i nf or me d c o nse nt, baseli ne i nf or mati o n, 
a n d ot her relate d f or ms u p t o t he p oi nt of scree n fail  
•  “ A d vers e E ve nt” f or m (s) f or a n y re p orta ble e ve nt, as defi ne d i n Secti o n 2 1 , f or a n y 
a d verse e ve nt t hat oc c urs after si g ni n g t he inf or me d co nse nt, u p t o t he p oi nt of s cree n 
fail  
1 0. 2. 2.  R a n d o mize d  
Pri or t o ra n d o mizati o n, t he pla n ne d a bl ati o n pr oce d ure t y pe, c o nc o mita nt or se q ue ntial, m ust 
be s pecifie d. A ra n d o mize d s u bject is a s u bject w h o si g ns i nf or me d c o nse nt a n d is 
ra n d o mize d.  S u bjects m ust n ot be ra n d o mize d u nless t he y ha ve a v ali d a n d si g ne d i nf or me d 
c o nse nt a n d meet all i ncl usi o n a n d n o e xcl usi o n criteria.   
 
F or s u bjects i n t he se q u e ntial gr o u p, ra n d o mizati o n ca n o nl y occ ur bet wee n 9 0 a n d 1 8 0 da ys  
f oll o wi n g t he m ost rece nt A F a blati o n pr oce d ure. S u bjects w h o are pla n ni n g t o ha ve a 
c o nc o mita nt pr oce d ure m ust be ra n d o mize d wit h i n 1 0 da ys pri or t o t he pla n ne d a blati o n 
pr oce d ure .  All s u bjects  (c o nc o mita nt or se q ue ntial) ra n d o mize d t o t he De vice Gr o u p are 
re q uire d t o u n der g o W A T CH M A N  F L X  De vice  i m pla nt wit hi n 1 0  cale n dar da ys of 
ra n d o mizati o n.  B ot h gr o u ps  are f oll o w e d i n acc or da nce wit h t he f oll o w-u p  sc he d ule.  Al l 
a p plica ble case re p ort f or ms per t he pr ot oc ol m ust be c o m plete d. T he ori gi nal si g ne d 
inf or me d co nse nt a n d a n y rele va nt d oc u m e ntati o n m ust be mai ntai ne d i n t he site’s s u bject 
file. 
1 0. 2. 3.  De vice Gr o u p Cl assific ati o ns  
S u bjects ra n d o mize d t o t he D e vic e G r o u p a n d R oll -I n s u bjects will be f urt h er classifie d as 
eit her a n i nte nt, atte m pt, or i m pla nt.  After st u d y e nr oll me nt c o m pleti o n, if t he classificati o n 
is t o be u p date d b y t he site, t he site will c o ntact t he st u d y tea m directl y f or f urt her 
i nstr ucti o n.  
1 0. 2. 3. 1.  I nte nt 
A Ra n d o mize d s u bject i n t he De vice Gr o u p t hat d oes n ot ha ve a n i m pla nt atte m pt ( i.e., 
W A T C H M A N Access S heat h is ne ver i nserte d i nt o t he b o d y) will be classifie d as a n “I nte nt” 
s u bject.  T he reas o n f or t he I nte nt will be c ollect e d i n t he data base.  I nte nt s u bjects c o u nt 
t o war ds t he e nr ollme nt  ceili n g a n d will be use d f or a nal yses of t h e e n d p oi nts  acc or di n g t o 
i nte nti o n-t o -treat pri nci ples.  I nt e nt s u bjects will  be f oll o we d acc or di n g t o t he f oll o w -u p 
sc he d ule wit h t he e x ce pti o n of t he f oll o w-u p L A A i ma gi n g.  Inte nt s u bjects are n ot r e q uire d 
t o ha ve t he 3-m o nt h a n d 1 2 -m o nt h f oll o w -u p L A A i ma gi n g. I nte nt s u bjects are n ot re q uire d 
t o f oll o w t he De vice Gr o u p me dicati o n re q uir e me nts, b ut a nti platelet, N S AI Ds, 
a ntic oa g ula nt , a n d a ntiarr h yt h mic me dicati o ns m ust be ca pt ure d i n t he m e dicati o n l o gs .  All 
a p plica ble case re p ort f or ms per t he pr ot oc ol m ust be c o m plete d. T he ori gi nal si g ne d 
inf or me d co nse nt a n d a n y rele va nt d oc u m e ntati o n m ust be mai ntai ne d i n t he site’s s u bject 
file. 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 4  of 1 0 2  
  
1 0. 2. 3. 2.  Atte m pt  
A Ra n d o mize d s u bject i n t he De vice Gr o u p t hat  h as ha d t he W A T C H M A N Access S heat h 
i nserte d i nt o t he b o d y i n or der t o i m pla nt t he de vi ce, b ut e ve nt u all y d oes n ot recei ve a 
W A T C H M A N F L X D e vice will be classifie d as “ Atte m pt .”  Atte m pt s u bjects c o u nt t o war ds 
t he e nr ollme nt  ceili n g a n d will be use d f or a n al yses of t he e n d p oi nts  acc or di n g t o i nte nti o n -t o 
-treat pri nci ples.  Atte m pt s u bjects will  be f oll o we d acc or di n g t o t he f oll o w -u p sc he d ule wit h 
t he e xce pti o n of t he f oll o w-u p L A A i ma gi n g.  Att e m pt s u bjects are n ot r e q uire d t o ha ve t he 
3 -m o nt h a n d 1 2 -m o nt h f oll o w -u p L A A i ma gi n g. Atte m pt s u bjects are n ot re q uire d t o f oll o w 
t he De vice Gr o u p me dicati o n re q uire me nts, b ut a nti platelet, N S AI Ds, a ntic oa g ula nt, a n d 
a ntiarr h yt h mic me dicati o ns m ust be ca pt ure d i n t h e me dicati o n l o gs .  All a p plica ble cas e 
re p ort f or ms p er t he pr ot oc ol m ust be c o m plete d. T he ori gi nal si g ne d inf or me d co nse nt a n d 
a n y rele v a nt d oc u me ntati o n m ust be mai ntai ne d i n t he site’s s u bject file. 
1 0. 2. 3. 3.  I m pla nt 
A s u bject w h o is s uccessf ull y i m pla nte d wit h t he W A T C H M A N  F L X D e vice will be 
classifie d as a n “I m pla nt. ” T hese s u bjects are f oll o we d i n acc or da n ce wit h t he f oll o w-u p  
sc he d ule.  All a p plica bl e case re p ort f or ms p er t he pr ot oc ol m ust be c o m plete d. T he ori gi nal 
si g ne d inf or me d co nse nt a n d a n y rel e va nt d oc u me ntati o n m ust be mai ntai ne d i n t he site’s 
s u bject file. 
1 0. 3.  St u dy C o m pleti o n, Wit h dr a w al , or L ost t o F oll o w-U p  
W hile all eff orts will be ma de t o mi ni mize attriti o n, s u bjects ma y wit h dra w fr o m t he st u d y at  
a n y ti me, wit h or wit h o ut reas o n a n d wit h o ut prej u dice t o f urt her treat me nt. Wit h dra w n  
s u bjects will n ot u n der g o a n y a d diti o nal st u d y f oll o w-u p, n or will t he y be re place d. All 
s u bjects e nr olle d i n t he cli nical st u d y (i ncl u di n g t h ose wit h dra w n fr o m t he cli nical st u d y or 
l ost t o f oll o w-u p) s hall be acc o u nte d f or a n d d oc u me nte d.   W he n st u d y s u bjects c o m plete t he 
st u d y per t he pr ot oc ol r e q uire me nts, t heir partici p ati o n i n t he st u d y is c o nsi dere d as 
c o m plete, a n d t he y will b e e xite d fr o m t he st u d y.  
 
If a s u bject wit h dra ws fr o m t he cli nical i n vesti gati o n, t he reas o n(s) m ust  be re p ort e d. If s uc h 
wit h dra wal is d ue t o pr o ble ms relate d t o de vice safet y or perf or ma nce, t he i n vesti gat or m ust 
as k f or t he s u bject’s per missi o n t o f oll o w his/ her stat us/c o n diti o n o utsi de of t he cli nical 
st u d y. T his re q uest nee ds t o be d oc u me nte d i n t he s u bject file.  
 
T he s p o ns or ma y as k t hat wit h dra w n s u bjects are f oll o we d f or i nf or mati o n r elate d t o t he 
safet y of t he de vice, if a v aila ble.  
 
Reas o ns f or st u d y e xit will be ca pt ure d i n t he E D C data base a n d ma y i ncl u d e, p h ysicia n 
discreti o n, s u bject c h oice t o wit h dra w c o nse nt, l ost t o f oll o w -u p, or deat h. W hile st u d y e xit is 
disc o ura ge d, s u bjects ma y wit h dra w fr o m t he st u d y at a n y ti me, wit h or w it h o ut reas o n, a n d 
wit h o ut prej u dice t o f urt her treat me nt.  
 
All a p plica ble cas e re p ort f or ms m ust be c o m plete d at st u d y e xit (i.e., wit h dra wal, deat h, 
st u d y c o m pleti o n) a n d a n “ E n d of St u d y” f or m m ust be c o m plete d. S u bjects w h o are “l ost -t o-

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 5  of 1 0 2  
  
f oll o w-u p” m ust ha ve d o c u me nte d at least t hree atte m pts t o c o ntact t he m pri or t o c o m pleti o n 
of t he “ E n d of St u d y” f or m.  S h o ul d t he s u bject c o nti n ue t o be u nreac ha ble, he or s he will be 
c o nsi dere d t o ha v e wit h dra w n fr o m t he st u d y wit h t he pri mar y reas o n of l ost t o f oll o w u p.  
Data c ollecte d u p t o t he p oi nt of s u bject wit h dra wal ma y be use d f or st u d y a nal ysis u nless  
l ocal re g ulati o ns pr o hi bit its use. 
 
At t he p oi nt of st u d y c o m pleti o n a n d/ or wit h dra wal , all a d verse e v e nts m ust be assesse d b y 
t he i n vesti gat or. T hese e ve nts m ust be cl ose d or d oc u me nte d as c hr o nic. F or t h ose e ve nts t hat 
ha ve bee n assesse d as rel ate d t o t he de vice , t hese s h o ul d be f oll o we d t hr o u g h res ol uti o n if 
p ossi ble a n d c o nse nt has bee n pr o vi de d b y t he s u bject f or dat a c ollecti o n o n t hese e ve nts.   
1 0. 4.  E n d of St u dy Acti o n Pl a n  
At t he c o ncl usi o n of t he st u d y, patie nts recei vi n g a de vice s h o ul d be f oll o we d per sta n d ar d of 
care practices at t he ir site.   
1 1.  St u d y Met h o ds  
1 1. 1.  D at a C ollecti o n –  R oll -I n S u bjects 
R oll -I n s u bjects m ust meet all i ncl usi o n a n d n o ne of t he e xcl usi o n criteria a n d  will n ot be 
ra n d o mize d.  F or all I nte nt, Atte m pt, a n d I m pla nt s u bjects (s uccessf ull y recei ve d t he 
W A T C H M A N F L X D e vice) all visits are re q uire d, as defi ne d i n Ta bl e 1 1. 2 -1 .  Ho we v er, 
I nte nt a n d Atte m pt s u bje cts d o n ot re q uire L A A  i ma gi n g at 3 a n d 1 2 m o nt hs. 
St u d y pr oce d ures a n d f oll o w -u p visits will occ ur as f oll o ws:  
 
Ta ble 1 1. 1 -1 : R oll -I n St u d y Visits  
Visit  
Ti mefra me  
C o nse nt  
M ust be perf or m e d wit hi n 4 0 da ys pri or t o i m pla nt  
Pre -pr oce d u re L A A 
I ma gi n g ( T E E or C T) 
- O pti o nal f or T E E g ui de d W A T C H M A N F L X i m pla nts  
- Re q uire d f or I C E g ui de d W A T C H M A N F L X i m pla nts ( m ust 
be perf or me d after c o ns e nt a n d pri or t o i m pla nt) . T hese L A A 
i ma gi n g will be c ollecte d acc or di n g t o t he I m a gi n g Ma n ual a n d 
s u b mitte d t o t he C ore La b f or re vie w 
I m pla nt 
- Pri or a blati o n ( Se q ue nti al Gr o u p ) –  T h e W A T C H M A N F L X 
i m pla nt pr oce d ure m ust be perf or me d bet w ee n 9 0 a n d 1 9 0 da ys 
of t he m ost rece nt A F a bl ati o n pr oce d ure  
- Pla n ne d a blati o n ( C o nc o mita nt Gr o u p ) –  T he a bl ati o n a n d 
W A T C H M A N  F L X im pla nt m ust be perf or m e d wit hi n 4 0 da ys 
of c o nse nt  
3 -M o nt h F oll o w -u p  
9 0 ± 1 5 da ys fr o m i m pla nt 
1 2 -M o nt h F oll o w -u p  
3 6 5 ± 3 0 da ys fr o m i m pla nt 
2 4 -M o nt h F oll o w -u p  
7 3 0 ± 6 0 da ys fr o m i m pla nt 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
 
             
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 6  of 1 0 2  
  
Visit  
Ti mefra me  
3 6 -M o nt h F oll o w -u p  
1 0 9 5 +  6 0 da ys fr o m  i m pla nt - t his f oll o w-u p m ust occ ur o n or 
after 1 0 9 5 d a ys a n d o n or bef ore 1 1 5 5 d a ys  
 
1 1. 2.  D at a C ollecti o n  –  R a n d o mize d S u bjects  
F or all I nte nt, Atte m pt , a n d I m pla nt s u bjects (s uccessf ull y recei ve d t he W A T C H M A N F L X 
De vice) all visits are re q uire d, as defi n e d i n  Ta ble 1 1. 2 -1 . H o we v er, Inte nt  a n d Atte m pt  
s u bjects d o n ot re q uire L A A i ma gi n g at 3 a n d 1 2 m o nt hs. 
St u d y pr oce d ures a n d f oll o w -u p visits will occ ur as f oll o ws:  
 
Ta ble 1 1. 2 -1 : Ra n d o mize d S u bject St u d y Visits  
Visit  
Ti mefra me  
C o nse nt  
M ust be perf or m e d wit hi n 3 0 da ys pri or t o ra n d o mizati o n 
Ra n d o mizati o n  a n d 
I m pla nt 
- Pri or a blati o n ( Se q ue nti al gr o u p) –  ra n d o mizati o n m ust be 
perf or me d b et wee n 9 0 a n d 1 8 0 da ys after t he m ost rece nt A F 
a blati o n pr oce d ure. W A T C H M A N F L X im pla nt m ust be 
perf or me d wit hi n 1 0 da ys f oll o wi n g ra n d o mizati o n  
- Pla n ne d a blati o n ( C o nc o mita nt gr o u p) –  t he a blati o n +/- 
W A T C H M A N F L X i m pla nt m ust be perf or m e d wit hi n 1 0 da ys 
of ra n d o mizati o n  
Pre -pr oce d u re L A A 
I ma gi n g ( T E E or C T) 
- O pti o nal f or T E E g ui de d W A T C H M A N F L X i m pla nts  
- Re q uire d f or I C E g ui de d W A T C H M A N F L X I m pla nts ( m ust 
be perf or me d after ra n d o mizati o n a n d pri or t o i m pla nt) . T hese 
L A A i ma gi n g will be c ollecte d acc or di n g t o t he I ma gi n g 
Ma n ual a n d s u b mitte d t o t he C ore La b f or re vi e w  
3 -M o nt h F oll o w -u p  
9 0 ± 1 5 da ys fr o m ra n d o mizati o n  
1 2 -M o nt h F oll o w -u p  
3 6 5 ± 3 0 da ys fr o m ra n d o mizati o n  
2 4 -M o nt h F oll o w -u p  
7 3 0 ± 6 0 da ys fr o m ra n d o mizati o n  
3 6 -M o nt h F oll o w -u p  
1 0 9 5 +  6 0 da ys fr o m r a n d o mizati o n  - t his f oll o w-u p m ust occ ur 
o n or after 1 0 9 5 da ys a n d o n or bef ore 1 1 5 5 da ys  
N ote: Baseli ne data c ollecti o n  n ot a vaila ble pri or t o c o nse nt  m ust occ ur  wit hi n 3 0 da ys pri or t o 
ra n d o mizati o n.  St u d y-s pecific pr oce d ures t hat are n ot sta n dar d of care m ust o nl y be perf or me d after 
t he patie nt has si g ne d i nf or me d c o nse nt.

 
C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
 
            
    
 
 
 
 
 
 
 
     O P TI O N Pr ot oc ol, d o c u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 4 7  of 1 0 2  
  
Ta ble 1 1. 2 -2 : Dat a C ollecti o n Sc he d ule  
Pr o ce d ure/ Assess m e nt  
B aseli ne 
Assess m e nt  ( Pri or 
t o R a n d o miz ati o n) 
 
I n de x Pr oce d ure 
(A bl ati o n 
Pr oce d ure +/ - 
W A T C H M A N 
F L X ) 
F oll o w -u p Visits * * * * *  
3 -M o nt h 
F oll o w -
u p  
1 2 -M o nt h 
F oll o w -
u p  
2 4 -M o nt h 
F oll o w -u p  
3 6 -M o nt h 
F oll o w -u p  
I nf o r m e d c o nse nt pr ocess, i n cl u di n g i nf o r m e d 
c o nse nt si g n at ure d ate  
X  
-- 
-- 
-- 
-- 
-- 
De m o gr a p hics  
X  
-- 
-- 
-- 
-- 
-- 
P h ysic al assess m e nt  
X  
D G  a n d C C  
X  
X  
X  
X  
Me dic al hist or y  
X  
-- 
-- 
-- 
-- 
-- 
A bl ati o n I nf or m ati o n  
X   
C C  
O  
O  
O  
O  
D e vice i nf o r m ati o n  
-- 
D G   
-- 
-- 
-- 
-- 
Pr o ce d ure i nf o r m ati o n a n d disc h ar g e assess m e nt  
 
D G a n d C C  
 
 
 
 
T T E  
X * * *  
-- 
-- 
-- 
-- 
-- 
Pre -pr oce d ure L A A i m a gi n g  ( T E E or C T) 
-- 
D G ^  
-- 
-- 
-- 
-- 
I m pl a nt Pr o ce d u re T E E /I C E 
-- 
D G  
 
 
 
 
F oll o w -u p L A A i m a gi n g ( T E E or C T)  
-- 
-- 
D G *  
D G *  
O  
O  
Br ai n I m a gi n g ( C T or M RI)  
O * *  
O * *  
O * *  
O * *  
O * *  
O * *  
Ser u m Cre ati ni ne or G F R/e G F R  
X  
-- 
-- 
-- 
-- 
-- 
Pl atelet c o u nt a n d He m o gl o bi n le vel  
X  
-- 
-- 
-- 
-- 
-- 
NI H Str o k e Sc ale  
X  
-- 
X  
X  
X  
X  
M o difie d R a n ki n Sc ale * * * *  
X  
-- 
X  
X  
X  
X  
Q o L ( E Q -5 D/ S F 1 2)  
X  
-- 
-- 
X  
-- 
X  
Me dic ati o n Re gi m e n Re vie w  
X  
X  
X  
X  
X  
X  
A d verse e v e nt assess m e nt  / d e vice deficie nc y 
m o nit o ri n g  ( as a p plic a ble) 
X  
X  
X  
X  
X  
X  
X = All s u bjects; D G = De vic e Gr o u p ; C C = C o nc o mita nt; O = O pti o nal, data is c ollecte d if a vaila ble  
*I m pla nt s u bjects o nl y  ( d oes n ot i ncl u de I nte nts or Atte m pts) 
* * F or s u bjects wit h pri or str o ke or TI A, pri or M RI/ C T sca ns ma y be re q ueste d b y B S C.  F or s u bjects w h o ha v e a ne ur ol o gic e v e nt d uri n g t he trial,  a c o p y of  
pri or M RI/ C T sca ns a n d M RI/ C T sca ns fr o m t he e ve nt ma y be re q ueste d . 
* * * T he baseli ne T T E will be d o ne t o e v al uate all e xcl usi o n criteria t o c o nfir m s u bject eli gi bilit y    Ot her rece nt car diac i ma gi n g ma y be use d t o e v al uate 
e x cl usi o n criteria if a vaila ble i n t he s u bject’s me dical rec or d.   (see Secti o n 1 1.1 0 . 1 f or a d diti o nal details). 
^ Pre -pr oce d ure L A A i ma gi n g ( T E E or C T) is re q uire d f or I C E g ui de d W A T C H M A N F L X i m pla nts a n d o pti o n al  f or T E E-g ui de d W A T C H M A N F L X i m pla nts . 

 
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* * * * M o difie d Ra n ki n Scale ma y be c o m plete d via tele healt h or p h o ne at t he discreti o n of a certifie d,  trai ne d st u d y pers o n nel.  
* * * * *  P h ysical e x a m  a n d NI H str o ke scale ma y n ot be c o m plete d re m otel y if f oll o w u p visit is c o n d ucte d via p h o ne.  Q o L ma y be c o m plete d re m otel y if p h o ne 
i nter vie w scri pt is utilize d.  

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1 1. 3.  St u dy C a n di d ate Scree ni n g  
S u bjects selecte d f or partici pati o n i n t his st u d y ma y be fr o m t he i n vesti gat or’s ge neral n o n -
val v ular atrial fi brillati o n p o p ulati o n .  Eac h i n vesti gat or is res p o nsi ble f or selecti n g t h ose 
w h o are a p pr o priat e f or i ncl usi o n.  
 
All s u bjects t hat si g n t he I C F will be e ntere d i n t he E D C data bas e.  S u bjects w h o si g n t he 
I C F b ut w h o are n ot ra n d o mize d will be c o nsi dere d scree n fail ure s u bjects a n d d oc u me nte d 
as s uc h i n t he E D C data b ase.  Scree n fail ure  s u bjects s h o ul d be e xite d i m me diatel y u p o n 
deter mi ni n g i neli gi bilit y .     
1 1. 4.  I nf or me d C o nse nt 
S u bjects t hat ha ve si g ne d a n d date d t he I C F are c o nsi dere d e nr olle d i n t he st u d y.  T he 
i nf or me d c o nse nt pr o cess m ust be d oc u me nte d b y t he pers o n o btai ni n g c o nse nt a n d t he 
d oc u me ntati o n m ust be place d i n t he s u bject’s file.  
1 1. 5.  B aseli ne Assess me nt  Wi n d o w  
Eac h s u bject h as a ma xi m u m of 3 0 da ys t o c o m plete t he baseli ne assess me nt  f oll o wi n g 
c o nse nt . T he i nf or m ati o n bel o w will be d oc u me nt e d o n case re p ort f or ms f or e nr olle d 
s u bjects: 
•  De m o gra p hics d ata i ncl u di n g a ge at ti me of c o ns e nt, se x, race, a n d et h nicit y  
•  Me dical, car diac,  a n d ne ur ol o gical hist or y  i ncl u di n g: car di o vasc ul ar diseas es; A F 
t y pe ( par o x ys mal/ persiste nt/l o n g sta n di n g persiste nt) a n d ti me si nce A F dia g n osis ; 
pri or hist or y of isc he mic str o ke, he m orr h a gic str o ke a n d/or TI A; pre vi o us car diac 
pr oce d ures; hist or y of blee di n g a n d l ocati o n ; N S AI D use; r is k f act ors, i ncl u di n g t h ose 
use d t o calc ulate H A S -B L E D, a n d C H A 2D S 2-V A Sc   
•  A blati o n i nf or mati o n i ncl u di n g a blati o n t y pe, s uccess, a n d r h yt h m p ost -a blati o n  
•  P h ysical assess me nt  i ncl u di n g vital si g ns, hei g ht, wei g ht, a n d r h yt h m  
•  C urre nt me dicati o n re gi me n  re vie w f or t he use of ant i platelet, a ntic oa g ul a nt, a n d 
a ntiarr h yt h mic  me dicati o ns   
•  M o difie d Ra n ki n Scale ( M R S) a n d NI H Str o ke Scale ( NI H S S) * *   
•  Q ualit y of Life Q uesti o n naire s ( S F-1 2/ E Q 5 D) * *  
•  Ser u m  Creati ni ne  or  Gl o mer ular filtrati o n rate  (G F R /e G F R).  L a b val ues ma y c o me 
fr o m me dical r ec or d if l a b test was perf or me d n o greater  t ha n 2 1 0 da ys pri or t o 
ra n d o mizati o n.  Ot her wise, la b val ues m ust be o bt ai ne d d uri n g t he bas eli ne 
assess me nt wi n d o w . Ser u m creati ni ne s h o ul d be rec or de d if a vaila ble.  If s er u m 
creati ni ne is n ot a v aila ble b ut e G F R is, e G F R s h o ul d be rec or de d.  
•  Platelet c o u nt a n d He m o gl o bi n le vel .  L a b val ues ma y c o me fr o m me di cal rec or d if 
la b test was perf or me d n o greater t ha n 7 da ys pri or t o i nf or me d c o nse nt.  Ot her wise, 
la b val ues m ust be o btai n e d d uri n g t he baseli ne assess me nt wi n d o w.  

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•  Tra nst h oracic Ec h o car di o gra m (T T E) * :  F or ec h o e xcl usi o n criteria assess me nt of 
E F, mitral ste n osis, pericar dial e ff usi o n, a n d P F O.  
 
 
* N ote:  T h e baseli ne T T E will be d o ne t o e val uat e all e xcl usi o n criteria t o c o nfir m s u bject 
eli gi bilit y.  Criteria o btai ne d fr o m a car diac i ma gi n g  perf or me d wit hi n 1 8 0  da ys pri or t o 
ra n d o mizati o n ma y be us e d if all t he e xcl usi o n criteria ca n be e v al uate d .  If all e xcl usi o n 
criteria w ere n ot o btai n e d o n t he pri or car diac i m a gi n g , a T T E will ha ve t o be c o n d ucte d 
at baseli ne. If a si g nifica nt car diac e ve nt occ urs after t he car diac i ma gi n g  w hic h ca uses a 
c ha n ge i n c ar diac stat us [i.e., maj or C o n gesti ve Heart Fail ure ( C H F) dec o m pe nsati o n] t he 
baseli ne T T E m ust be re peate d after i nf or me d c o nse nt a n d pri or t o ra n d o mizati o n  
 
* * N ote: T he pers o n a d mi nisteri n g t he Q ualit y -of -Life  Q uesti o n nair es a n d str o ke scales 
s h o ul d be bli n de d t o t he s u bject’s treat me nt assi g n me nt.  
1 1. 6.  R a n d o miz ati o n  
Ra n d o mizati o n will occ ur after all cli nical a n d tr a nst h oracic ec h o criteria h a ve bee n verifi e d  
a n d t he baseli ne assess me nt is c o m plete .  Ra n d o mizati o n will occ ur n o l ater t ha n 3 0 da ys 
f oll o wi n g c o nse nt.  S u bjects will be ra n d o mize d 1: 1 ( D e vice : C o ntr ol) a n d r a n d o mizati o n 
will be stratifie d b y se q u e ntial vs. c o nc o mita nt pla n ne d a blati o n t o hel p e ns ure bala nce of 
treat me nt assi g n me nts wit hi n t he se q ue ntial a n d c o nc o mita nt gr o u ps. 
1 1. 6. 1.  Se q ue nti al  A bl ati o n gr o u p  
Ra n d o mizati o n m ust occ ur bet wee n 9 0 a n d 1 8 0 d a ys after t h e m ost rece nt A F a blati o n 
pr oce d ure.  If t h e s u bject is ra n d o mize d t o t he de vi ce gr o u p, im pla nt m ust occ ur wit hi n 1 0  
da ys of ra n d o mizati o n.   
 
F or roll -in s u bjects, t he i m pla nt m ust occ ur bet wee n 9 0 a n d 1 9 0 da ys after t he m ost rece nt 
A F a blati o n.  
1 1. 6. 2.  C o nc o mit a nt  A bl ati o n gr o u p  
Ra n d o mizati o n m ust occ ur wit hi n 1 0 da ys pri or t o t he pla n ne d a blati o n .  If t he s u bject is 
ra n d o mize d t o t he de vi ce gr o u p, cat heter a blati o n a n d device i m pla nt m ust occ ur wit hi n 1 0  
da ys of ra n d o mizati o n.   
1 1. 7.  I n de x Pr oce d ure 
F or all patie nts  u n der g oi n g a blati o n a n d/ or W A T C H M A N  F L X  i m pla ntati o n, t he f oll o wi n g 
data will be c ollecte d:  
•  P h ysical assess me nt  i ncl u di n g vital si g ns, wei g ht, a n d r h yt h m at ti me of t he 
pr oce d ure  

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•  C urre nt me dicati o n re gi me n  re vie w f or t he use of ant i platelet, N S AI D, a ntic oa g ula nt, 
a n d a ntiarr h yt h mic  me di cati o ns   
•  A blati o n i nf or mati o n ( patie nts u n der g oi n g A blati o n ) i ncl u di n g a blati o n t y pe, s uccess, 
a n d r h yt h m p ost -a blati o n  
•  A d verse e ve nts e x perie n ce d at i n de x pr oce d ure a n d si nce e nr oll me nt. Refer t o Secti o n 2 1  
f or detaile d inf or mati o n o n Safet y re p orti n g  
•  Disc har ge i nf or mati o n ( date, ti me)  
 
F or patie nts u n der g oi n g W A T C H M A N  F L X  i m pla ntati o n, t he pr oce d ure s h o ul d be 
perf or me d usi n g sta n d ar d of care met h o ds esta blis he d b y t he i n vesti gati o nal site ( e. g., sterile 
tec h ni q ue, pers o n n el re q uire me nts, etc.).  I m pl a ntati o n of t he W A T C H M A N F L X De vice 
s hall o nl y be perf or m e d b y st u d y p h ysicia ns trai ne d i n perc uta ne o us a n d tr a nsse ptal 
pr oce d ures w h o ha v e c o m plete d t he W A T C H M A N  a n d/ or W A T C H M A N F L X  p h ysicia n 
trai ni n g pr o gra ms. Refer t o t he W A T C H M A N F L X I nstr ucti o ns f or Us e (IF U) f or detaile d 
i nstr ucti o ns re gar di n g t he i m pla ntati o n a n d use of t he W A T C H M A N F L X De vice.    
 
N otes:  
1.  T E E is rec o m me n de d f or i m pla nt pr oce d ures; h o w e ver, i ntracar di ac ec h ocar di o gra p h y 
(I C E) is a n acce pt a ble alt er nati ve a n d m a y be use d if t he f oll o wi n g c o n diti o ns are met: 
•  Pre -pla n ni n g L A A i ma gi n g usi n g T E E or C T m ust be c o m plete d pri or t o t h e i m pla nt 
pr oce d ure.  
•  T he i m pla nti n g p h ysicia n m ust ha ve perf or me d ≥ 2 5 W A T C H M A N a n d/ or 
W A T C H M A N F L X pr oce d ures t hat i n v ol ve t he us e of I C E.  
•  If I C E is use d, t he site m ust perf or m pre -pla n ni n g L A A i ma gi n g a n d m ust s pecif y i n 
t he e C R F w hat i ma gi n g m o dalit y was use d . 
 
2.  D o n ot pr ocee d  wit h t he W A T C H M A N F L X i m pla nt if t he f oll o wi n g is o bser ve d o n 
T E E /I C E or fl u or osc o p y:  
•  Intr acar diac t hr o m b us, L A A sl u d ge ( gelati n o us, n o n-a d here nt, i ntraca vitar y 
ec h o de nsit y m ore la y ere d t ha n de nse s p o nta ne o us ec h o c o ntr ast ( S E C) see n 
c o nti n u o usl y t hr o u g h o ut car diac c ycl e) or d e nse S E C.  
•  C o m ple x at her o ma wit h m o bile pla q ue of t he des ce n di n g a orta a n d/ or a ortic arc h.  
•  T he L A A a n at o m y will n ot acc o m m o date a W A T C H M A N F L X cl os ure de vic e. 
•  Hi g h -ris k P F O n ot dete cte d at baseli ne. 
 
A d diti o nal data c ollecte d f or patie nts  u n der g oi n g W A T C H M A N F L X i m pla ntati o n : 
•  W A T C H M A N F L X De vice usa ge i nf or m ati o n , i ncl u di n g de vice size a n d c o m pressi o n 
p ost -i m pla nt ( De vice Gr o u p o nl y); 
•  Access S yste m(s) us a ge i nf or mati o n   
•  L A A i ma gi n g (as des cri b e d i n S ecti o n 1 1. 1 0 ): L A A size/s ha pe, n u m ber of l o bes i n 
L A A, a n d l oc ati o n of l o bes t o osti u m;  
•  De vice Rele ase Criteri a  
•  Na me of i m pla nti n g p h ysicia n  

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•  D urati o n of pr oce d ure a n d fl u or osc o p y  
•  Pr oce d ural me di cati o ns  
•  T y pe of a n est hesia  
•  De vice D eficie n cies  
•  Disc har ge i nf or mati o n  ( date, ti me) 
1 1. 8.  St u dy Me dic ati o n Re gi me n  
1 1. 8. 1.  De vice Gr o u p St u d y Me dic ati o n Re gi m e n  
After t he W A T C H M A N F L X i m pla nt, De vice Gr o u p  s u bjects will be pres cri be d mar k et -
a p pr o ve d O A C  a n d as piri n ( 7 5 -1 0 0 m g rec o m me n de d) u ntil t he 3 -m o nt h visit  f oll o we d b y 
as piri n u ntil  at least t he 1 2 -m o nt h visit (rec o m me n de d f or d urati o n of t he tri al ). 
 
A n y c ha n ges t o pr ot o c ol re q uire d me di cati o ns or a ntiarr h yt h mic me dicati o ns m ust be 
ca pt ure d i n t he a p pr o priate me dicati o n l o g.  
1 1. 8. 2.  C o ntr ol Gr o u p St u d y Me dic ati o n Re gi m e n  
F oll o wi n g ra n d o mizati o n, c o ntr ol s u bjects m ust  c o nti n ue or start mar ket a p pr o ve d  O A C use d 
per I F U f or atrial fi brillati o n str o ke pre ve nti o n  a n d s h o ul d re mai n o n it  f or t he d urati o n of t he 
trial. 
1 1. 9.  F oll o w -U p Pr oce d ures ( Office ( preferre d) or P h o ne c all) 
S u bjects will be f oll o we d at office visits  ( preferre d) or p h o ne visit at 3 m o nt hs ( 9 0  ± 1 5 da ys  
fr o m ra n d o mizati o n), 1 2 m o nt hs (3 6 5 ± 3 0  da ys  fr o m ra n d o mizati o n), 2 4 m o nt hs (7 3 0 ± 6 0 
da ys  fr o m ra n d o mizati o n), a n d 3 6 m o nt hs ( 1 0 9 5 +  6 0  da ys  fr o m ra n d o mizati o n - visit m ust 
occ ur o n or after da y 1 0 9 5 ). 
Data fr o m a p h ysical ass ess me nt t hat is  perf or me d at a n o utsi de facilit y /n o n st u d y trai ne d 
pers o n nel  as p art of t he p atie nt sta n dar d  of care, m a y be utilize d f or t h e p ur p ose of a 
pr ot oc ol -re q uir e d s u bject visit if c o m plete d wit hi n t he  f oll o w u p visit wi n d o w.  T hese dat a are 
t o be re vie we d b y a n i n v esti gat or o n t he dele gati o n l o g f or i ncl usi o n of dat a as part of t h e 
st u d y.   A n y ot her data t h at is c ollecte d fr o m a n o utsi de facilit y as part of t h e sta n dar d of care  
(s uc h as i ma gi n g) of t he patie nt ma y be c o nsi dere d  f or i ncl usi o n as part of t he  st u d y data.  
 
N ote: f or R oll -i n s u bjects t he date of i m pla nt will be use d t o calc ul ate F oll o w-u p wi n d o ws 
i nstea d of t he date of ra n d o mizati o n. 
 
T he f oll o wi n g will be ass esse d d uri n g eac h visit a n d d oc u me nte d o n case re p ort f or ms:  
•  R e-d o a blati o ns  
•  D oc u me nte d  atri al fi brillati o n  e pis o de si nce pri or visit  
•  N e w o nset atrial fl utter or atrial tac h ycar dia e v e nt ( ≥ 3 0 sec o n ds i n d urati o n or fr o m a 1 0 
sec o n d 1 2-le a d E K G; ele ctrical a n d/ or p h ar mac ol o gical car di o v ersi o n f or A F L/ A T )  

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•  L A A i ma gi n g (as des cri be d i n S ecti o n  1 1. 1 0 ) f or all I m pla nt p atie nts (s u b mitte d t o c ore 
la b).  L A A i ma gi n g  d ata will i ncl u de:  
o  D e vice p ositi o n  
o  L A A seal  stat us 
o  T hr o m b us o n t he de vice s urface  (if vis ualize d) 
o  Intr acar diac t hr o m b us  (if vis ualize d) 
o  R esi d ual atrial se ptal s h u nt  (if vis ualize d)   
•  * N ote –  L A A i ma gi n g m ust be perf or m e d at 3 -m o nt hs a n d 1 2 -m o nt hs f oll o w -u p.  If 
perf or me d at t he later visits or at t he ti me of a n a d verse e v e nt, t he i nf or mati o n will be 
c ollecte d i n t he data b ase.   I nte nt a n d Atte m pt patie nts will n ot ha ve 3 -m o nt h or 1 2 -
m o nt h L A A i ma gi n g  perf or me d. P h ysical assess me nt  i ncl u di n g vital si g ns, wei g ht, a n d 
r h yt h m at ti me of t he visit .  
•  M o difie d Ra n ki n Scale ( M R S) a n d Nati o nal I nstit utes of Healt h Str o ke Scale ( NI H S S) . 
N ote: NI H S S ma y n ot be perf or me d re m otel y as p art of a p h o n e visit f oll o w -u p.  
•  C urre nt me dicati o n re gi me n  f or t he use of ant i platelet, N S AI D, a ntic oa g ula nt, a n d 
a ntiarr h yt h mic  me dicati o ns .  D ose c ha n g es, me dicati o n i nterr u pti o ns, a n d me dicati o n  
cessati o n m ust be d oc u m e nte d  
•  Q ualit y of Life Q uesti o n naire s at 1 2-m o nt h  a n d 3 6 -m o nt hs . N ote: p h o ne i nter vie w scri pt 
will be  a vaila ble f or use.  
•  A d verse e ve nts si nce pre vi o us visit.  Refer t o Secti o n 2 1  f or detaile d inf or mati o n o n 
Safet y re p orti n g  
•  De vice D eficie n cies  
1 1. 1 0.  
L A A I m a gi n g ( T E E , I C E, a n d C T ) 
R oll -I n a n d De vice Gr o u p s u bjects ma y u n der g o pre -pla n ni n g L A A i ma gi n g (t y picall y T E E 
or C T ) pri or t o W A T C H M A N F L X De vice i m pla nt.  Pre -pla n ni n g L A A i ma gi n g is n ot 
re q uire d f or s u bjects u n d er g oi n g T E E g ui de d i m pla nts.  If pre-pla n ni n g i ma gi n g is 
perf or me d, sites m ust n ot e t his o n t he data c ollecti o n f or m a n d t he i ma gi n g st u d y s h o ul d be 
sa ve d a n d ma d e a vaila bl e t o t he s p o ns or u p o n re q uest. Pre -pla n ni n g L A A i ma gi n g is re q uire d 
f or s u bjects u n der g oi n g I C E g ui de d i m pla nts a n d m ust be perf or me d acc or di n g t o t he 
i ma gi n g ma n ual a n d se nt t o t he C ore La b.   
1 1. 1 0. 1.  B aseli ne Tr a nst h or acic Ec h oc ar di o gr a m ( T T E)  
 
T he baseli ne T T E will be d o ne t o e val uate all e xcl usi o n criteria a n d t o c o nfir m s u bject 
eli gi bilit y.  Criteria o btai ne d fr o m a car diac i ma gi n g  perf or me d wit hi n 1 8 0 da ys  pri or t o 
ra n d o mizati o n ma y be us e d if all t he e xcl usi o n criteria ca n be e v al uate d .  If all e xcl usi o n 
criteria w ere n ot o btai n e d o n t he pri or car diac i m a gi n g , a T T E will ha ve t o be c o n d ucte d at 
baseli ne .  If a si g nifica nt car diac e ve nt o cc urs after t he car diac i ma gi n g  w hi c h ca uses a 
c ha n ge i n c ar diac stat us [i.e., maj or C o n gesti ve Heart Fail ure ( C H F) dec o m pe nsati o n] t he 
baseli ne T T E m ust be re peate d after i nf or me d c o nse nt a n d pri or t o ra n d o mizati o n . 
If a s u bject meet a n y of t he ec h o e xcl usi o n criteri a, t he y s h o ul d be scree n faile d a n d 
wit h dra w n i m me diatel y.  

C o nfi de ntial  
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1 1. 1 0. 2.  I m pl a nt a n d F oll o w-U p I m a gi n g  ( T E E/I C E/ C T) 
All pr ot oc ol re q uire d L A A i ma gi n g will be perf or me d i n acc or da nce wit h t he C ore La b  
I ma gi n g M a n ual.   
 
Im pla nt L A A i ma gi n g (T E E rec o m me n d e d) will all o w t he i n vesti gat or t o o btai n pr o per 
meas ure me nts of t h e L A A t o c orrectl y size t he de vice, c o nfir m d e vice release criteria are met 
pri or t o de vice releas e, d oc u me nt a bse nce of i ntracar diac t hr o m b us, a n d c o nfir m a d verse 
e ve nts ha ve n ot oc c urre d d uri n g t he i m pla nt pr oce d ure (i.e., p ericar dial eff usi o n).  
 
T E E is rec o m me n de d f or i m pla nt pr oce d ures; h o w e ver, I C E ma y b e use d b y  i n vesti gat ors 
t hat meet t he f oll o wi n g c o n diti o ns: 
•  Pre -pla n ni n g wit h T E E  or  C T m ust be perf or me d pri or  
•  T he i m pla nti n g p h ysicia n has perf or me d ≥ 2 5 W A T C H M A N a n d/ or 
W A T C H M A N F L X pr oce d ures t hat i n v ol ve t he us e of I C E  
 
T he 3 -m o nt h a n d 1 2-m o nt h L A A i ma gi n g ( T E E rec o m me n de d) is c o n d uct e d t o assess fl o w 
t hr o u g h a n d ar o u n d t he W A T C H M A N F L X D e vice a n d t o verif y t here is n o de vice relate d 
t hr o m b us ( D R T) o n t he s urface of t he d e vice.  A de q uate L A A s eal is defi n e d as 
de m o nstrati o n of peri -d e vice fl o w ≤5 m m  ar o u n d t he mar gi ns of t he W A T C H M A N F L X 
De vice.  
 
C o pies of all pr ot oc ol re q uire d L A A i ma gi n g m ust  be pr o vi de d t o t he c ore l a b per t he 
I ma gi n g M a n ual.  L A A Ima gi n g m ust be sa ve d a n d a vaila ble f or re vie w i n t he s u bject’s 
me dical or st u d y file.  Certai n i nf or mati o n fr o m t h e L A A i ma gi n g c o n d uct e d d uri n g t he 
c o urse of t he st u d y, i ncl u di n g a n y n o n -pr ot oc ol re q uire d  L A A  i ma gi n g (s uc h as t hat 
perf or me d i n t he c o nte xt of a n e m b olic e v e nt; see S ecti o n  1 1. 1 1. 2 ), will be ca pt ure d o n t he 
st u d y case re p ort f or ms a n d s u b mitte d t o t he c ore  la b.  All st u d y re q uire d i ma ges m ust be 
i de ntifie d as defi ne d i n t h e I ma gi n g Ma n ual.   
1 1. 1 1.  
Str o ke or Syste mic E m b olis m  
I n t h e e ve nt t hat a s u bject e x perie nces a str o k e or s yste mic e m b olis m ( S E) d uri n g t he c o urse 
of t he st u d y, s u p p orti n g d oc u me ntati o n will be re q ueste d b y t he s p o ns or i n a n atte m pt t o searc h 
f or ca us es of str o ke or e m b olic e ve nt.   
1 1. 1 1. 1.  Str o ke Sc ales  
T he Nati o nal I nstit utes of Healt h Str o ke Scal e ( NI H S S)  is a n assess me nt t o ol w hic h 
q ua ntifies str o ke -relate d ne ur ol o gical deficit.  It m ust be c o n d ucte d b y ne ur ol o gist or 
pers o n nel  w h o ha v e a c urre nt certificati o n t o c o n d uct t he NI H S S. It is r o uti nel y c ollecte d at 
Baseli ne a n d all offi ce  F oll o w -u p vi sits f or all s u bjects a n d s h o ul d be c oll ecte d at t he ti me of 
str o ke or TI A e ve nt.  If a d mi nistere d at t he ti me of e ve nt, t he NI H S S ma y be o btai ne d b y 
n o n -st u d y pers o n nel.  T h e M o difie d Ra n ki n Scale ( M R S) sc ore assess es t he se verit y of 
str o ke disa bilit y a n d f u ncti o nal de pe n de nce of all s u bjects.  T he assess me nt m ust be 

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perf or me d b y eit her a ne ur ol o gist or pers o n nel w h o ha ve c o m plete d a certificati o n f or t he 
M R S. T he M R S t o  be  c ollecte d at Baseli ne a n d F oll o w -u p visits  ( office or p h o ne) f or all 
s u bjects.  It m ust als o be c ollecte d  f oll o wi n g t he str o ke or TI A e ve nt a n d at 9 0 ( +/ - 1 5 ) da ys 
after a str o ke or TI A e v e nt.  T he M R S c ollecte d f oll o wi n g t he str o ke or TI A e ve nt, a n d at 9 0 
( +/- 1 5 ) da ys after a str o k e or TI A e ve nt ma y be o btai ne d b y n o n -st u d y pers o n nel.  
 
N ote: T he pers o n a d mi nisteri n g t he str o ke scal es s h o ul d be bli n de d t o t he s u bject’s treat me nt 
assi g n me nt.  
 
N ote: Ne ur ol o gic c o ns ult ati o n a n d cere bral vasc ul ar i ma g i n g s h o ul d be perf or me d if a 
s u bject’s NI H S S a n d M R S ha ve w orse n e d a n d / or if t here is s us pici o n of a n e ur ol o gic e ve nt.  
If ne ur ol o gic c o ns ultati o n a n d/ or cere bral vasc ular i ma gi n g d oes occ ur, B S C ma y re q uest a 
c o p y. 
1 1. 1 1. 2.  Str o ke or S yste mic E m b olis m a n d L A A I m a gi n g ( All s u bjects ) 
L A A i ma gi n g is str o n gl y e nc o ura g e d t o hel p bett er ascertai n t he mec ha nis m of t he str o ke or 
S E. T his is n ot re q uire d, h o we ver if c ollect e d t he i ma gi n g st u d y s h o ul d be sa ve d a n d se nt t o 
t he c ore la b p er I m a gi n g Ma n ual . A n o pti mal e v al uati o n i ncl u des, w here feasi ble b ase d o n 
s u bject stat us a n d tec h nic al c o nsi derati o ns, e v al uati o n of:  
•  L A t hr o m b us –  size, l ocati o n, m o bilit y, etc. 
•  A gitate d sali ne c o ntrast i njecti o n t o e val uate prese nce of resi d ual ri g ht t o left s h u nt at t he 
atrial le vel ( persiste nce of P F O or resi d ual p u nct ure h ole fr o m tra nsse ptal cat heterizati o n 
f or de vic e place me nt)  
•  Prese nce, l o cati o n, a n d gra de of asce n di n g a n d arc h a ortic at her o ma  
•  Prese nce of 
w orse ni n g left ve ntric ular d ysf u ncti o n, “ ne w” re gi o nal 
wall 
m oti o n 
a b n or malit y or pres e nce of L V t hr o m b us  
•  If a p plica bl e: 
•  W A T C H M A N F L X De vice seal or pres e nce (a n d meas ure me nt) of peri -de vice 
fl o w 
•  W A T C H M A N F L X D e vice t hr o m b us or pa n n us –  size, l ocati o n, m o bilit y, etc. 
1 1. 1 2.  
Devic e T hr o m b us  
T he m ost acc urate d eter mi nati o n of w het h er t hr o m b us has f or me d o n t he s urface of t he 
W A T C H M A N De vice is t hr o u g h T E E e v al uati o n.  I n t he case of t hr o m b us o n t he atrial faci n g 
si de of t he de vice, a ntic o a g ulati o n t hera p y s h o ul d be i nitiate d per h os pital sta n dar d of care, f or 
treat me nt of t hr o m b us.  After t he c o urse of a ntic oa g ulati o n t hera p y, a re peat i ma gi n g 
e val uati o n s h o ul d b e p erf o r me d t o c o nfir m t he t hr o m b us has res ol ve d. T his is n ot re q uir e d, 
h o we ver if c ollecte d t he i ma ge s h o ul d be sa ve d a n d se nt t o t he  c ore la b per I ma gi n g M a n ual . 
Cessati o n of a ntic oa g ulati o n after t his ti me p oi nt is at t he discreti o n of t he i n vesti gat or.  
 

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A n y i de ntificati o n of de vice t hr o m b us m ust be re p orte d o n a n a d v erse e ve nt C R F.  A c o p y of 
all i ma gi n g c o n d ucte d f or e val uati o n of p ote ntial t hr o m b us m ust be se nt t o t he Ec h o C ore La b 
a n d a c o p y m ust be mai ntai ne d i n t he s u bject’s rec or ds at t he site.  
 
T E E is rec o m me n de d f or f oll o w -u p i ma gi n g, b ut C T is a n acce pt a ble alter nati ve.  H o we v er, 
if fi n di n gs s us pici o us f or si g nifica nt D R T ( h y p oatte n uate d t hic ke ni n g ≥ 3 m m) or a n y 
pe d u nc ulate d t hr o m b us is n ote d o n C T at f oll o w-u p, a T E E m ust be perf or me d t o deter mi ne 
if t hera p y is re q uir e d. 
1 1. 1 3.  
Devic e Se al  
F or t h ose s u bjects recei vi n g a W A T H C M A N F L X de vice, i f a d e q uate d e vice seal  (i.e., n o 
lea k > 5 m m) is n ot o btai ne d as de m o nstrate d b y t he 3-m o nt h p ost -i m pla nt i ma gi n g (T E E  or 
C T) , t he decisi o n t o c o nti n ue or st o p O A C a n d/ or as piri n is at t he discreti o n of t he 
i n vesti gat or a n d s h o ul d be base d o n t he i n di vi d ual s u bject’s ris k/ be nefit a n al ysis (if p ossi ble, 
O A C s h o ul d ge nerall y be prescri be d) .  F oll o w -u p i ma gi n g ma y be perf or me d pri or t o t he 1 2 -
m o nt h visit t o reassess seal a n d i nf or m t he decisi o n t o st o p O A C a n d/ or as piri n.  If de vice 
seal is n ot o btai ne d as de m o nstrate d b y t he i nteri m or t he 1 2-m o nt h i ma gi n g (T E E  or C T) , 
t he decisi o n t o c o nti n ue or st o p O A C a n d/ or as piri n is at t he discreti o n of t he i n vesti gat or (if 
p ossi ble, O A C s h o ul d ge nerall y be prescri b e d) .        
 
N ote:  Cli nical st u d y data esta blis hi n g safet y a n d effecti ve n ess are base d o n de m o nstrati o n of 
peri -de vic e fl o w ≤5 m m as a meas ure of a de q uac y of L A A seal. Per t he W A T C H M A N F L X 
IF U, if a de q uat e seal is n ot de m o nstrate d, decisi o n t o disc o nti n ue O A C is at p h ysicia n 
discreti o n  pr o vi de d t hat a n y lea k de m o nstrate d is ≤ 5 m m . N o n-a p pr o ve d 
meas ures/ pr o ce d ures t o i m pr o ve seal ( e. g.  ‘ kissi n g’ W A T C H M A N, vasc ul ar pl u gs, 
e n d o vasc ular c oils, etc.) m ust n ot be atte m pte d d uri n g t he c o urse of t his st u d y.  
 
T E E is rec o m me n de d f or f oll o w -u p i ma gi n g, b ut C T is a n acce pt a ble alter nati ve.  H o we v er, 
if fi n di n gs s us pici o us f or si g nifica nt peri -de vi ce lea k ( P D L ) (e. g. lea k wi dt h > 3 m m) is n ote d 
o n C T at f oll o w -u p, a T E E m ust be perf or me d t o d eter mi ne if t hera p y is re q uire d. 
1 1. 1 4.  
St u dy C o m pleti o n  
All s u bjects will be f oll o we d t hr o u g h t he c o m pleti o n of t heir 3 -year f oll o w -u p visit , e xce pt 
f or Scree n Fail ure patie nts.  A n “ E n d of St u d y” f or m  will be c o m plete d t o d oc u me nt t he 
s u bject’s st u d y e xit. 
O nce a st u d y s u bject has e xite d t he st u d y, t heir partici pati o n i n t he st u d y has e n de d.  
A p pr o priate e C R Fs are c o m plete d i n dicati n g t he stat us of t he s u bject (i.e., e n d of st u d y 
f or m).  T he ta bl e bel o w pr o vi des i nf or mati o n o n t he a p pr o pri ate e C R Fs t o c o m plete. 
 
Ta ble 1 1. 1 4 -1 : St u d y E xit Data C ollecti o n Re q uire me nts  

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T y pe of St u d y E xit  
D ate t o Use  
F or m s t o c o m plete 
S u bject wit h dra wal  
Date of s u bject 
wit h dra wal  
•  
E n d of St u d y f or m  
•  
A d verse E ve nt (res ol ve d/cl ose a n y 
A E s or dee m c hr o nic ) 
S u bject L ost t o 
F oll o w -u p  
Date s u bject was last 
see n i n office or last 
p h o ne c o ntact  
•  
E n d of st u d y  
•  
A d ve rse E ve nt (res ol ve/cl ose a n y 
A E s or dee m c hr o nic ) 
S u bject Deat h  
Date of Deat h  
•  
A d verse E ve nt ( o nl y o ne) wit h fatal 
o utc o me, res ol ve/cl ose ot her A E s or 
dee m c hr o nic  
•  
E n d of St u d y F or m  
C o m plete all pr ot oc ol 
visits  
Date of last st u d y 
visit  
•  
E n d of St u d y F or m  
•  
A d ve rse E ve nt (res ol ve/cl ose a n y 
A E s or dee m c hr o nic ) 
Scree n Fail ure  
Date t he s u bject’s 
i neli gi bilit y is 
deter mi ne d  
•  
“ Scree n Fail ure” desi g nati o n o n 
“ Ra n d o mizati o n” f or m wit hi n t he 
“ Baseli ne” f ol der  
•  
E n d of St u d y F or m  
•  
A d verse E ve nt (res ol ve d/cl ose a n y 
A E s or dee m c hr o nic ) 
 
1 1. 1 5.  
S o urce D oc u me nts  
T he s p o ns or’s re pres e ntati ve, t he m o nit or, will perf or m o n g oi n g s o urce d ata verificati o n 
( S D V) a gai nst dat a tra ns cri be d t o e C R Fs. S o urce d ocu me nt s i ncl u de, b ut are n ot li mite d t o, 
h os pital rec or ds, cli nic/ office c h arts, st u d y s pecific w or ks heets, la b re p orts, s u bject 
q uesti o n naires, etc. S o ur ce d oc u me nts re q uire d t o verif y t he vali dit y a n d acc urac y of e C R F 
data m ust ne ver be o bliterate d or d estr o ye d. T o facilitate s o urce d oc u me nt verificati o n, t he 
I n v esti gat or/I nstit uti o n m ust pr o vi de S p o ns or & m o nit or direct access t o all s o urce 
d oc u me nts .   
 
W he n cli nical o bser vati o ns are e nt ere d dir ectl y i nt o a site’s E M R s yste m, t he electr o ni c 
rec or d ca n ser ve as t he s o urce d oc u m e nt if t he s yste m has bee n vali dat e d i n acc or da nce wit h 
I C H re q uire m e nts pertai ni n g t o c o m p uterize d s yste ms use d i n cli nical res earc h.  
A n acce pta ble c o m p uteri ze d data c ollecti o n s yste m (f or cli nical r esearc h p ur p oses) w o ul d be 
o ne t hat ( 1) all o ws dat a e ntr y o nl y b y a ut h orize d i n di vi d uals; ( 2) pre ve nts t he deleti o n or 
alterati o n of pre vi o usl y e ntere d data a n d pr o vi des a n a u dit trail f or s u c h d at a c ha n g es (e. g., 
m o dificati o n of file); ( 3) pr otects t he data base fr o m ta m peri n g; a n d ( 4) e ns ures data 
preser vati o n.  If a site’s c o m p uterize d me dical rec or d s yste m is n ot a de q uat el y vali date d f or 
t he p ur p oses of cli nic al r esearc h (as o p p os e d t o ge neral cli nical pr actice), a p plica ble 
har dc o p y s o ur ce d o c u me nts m ust be mai ntai ne d t o e ns ure t hat critical pr ot oc ol data 
tra nscri be d o n t he C R Fs ca n be v erifie d.  
 

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1 1. 1 6.  
L oc al L a b or at ory  
T his st u d y re q uires a l oc al la b orat or y.  A p pr o priat e l ocal la b orat or y certificati o ns a n d 
d oc u me ntati o n rec or ds are re q uir e d t o be mai ntai n e d a n d file d at t he site i n t he I n v esti gati ve 
Site File  t hr o u g h t he e nr oll me nt peri o d of t he st u d y. 
 
1 2.  C o ntr ol Gr o u p Cr oss o ver  
S u bjects ra n d o mize d t o t he C o ntr ol Gr o u p t hat e x perie nce a pri mar y efficac y e n d p oi nt e ve nt 
(str o ke [i ncl u di n g isc he mic a n d/ or he m orr h a gic], s yste mic e m b olis m) or pri mar y safet y e ve nt 
(I S T H maj or blee di n g, or cli nicall y rele va nt n o n-maj or blee di n g)  ma y be gi ve n t he o pti o n of 
recei vi n g a W A T C H M A N F L X  d e vice pri or t o st u d y c o m pleti o n.  Cr ossi n g o ver wit h o ut 
ha vi n g e x perie n ce d a n e n d p oi nt e ve nt is disc o ura g e d.  F or t h ose s u bj ects t hat cr oss o ver, t h e 
I n v esti gat or s h o ul d ta ke i nt o acc o u nt t he s u bject’s i n di vi d ual ris k/ be nefit pr ofile w he n 
deter mi ni n g t he ti mi n g of i m pla ntati o n after t he pri mar y e n d p oi nt e ve nt a n d ass ociate d 
me dicati o n.    
C o ntr ol Gr o u p s u bjects t hat recei ve a n y  L A A C  de vice will c o nti n ue t o be f oll o we d as 
C o ntr ol Gr o u p s u bjects a cc or di n g t o t he i nte nti o n -t o-treat pri nci ple a n d t heir assi g ne d s u bject 
visit wi n d o ws .  W A T C H M A N  F L X  I m pl a nt i nf or mati o n, i ncl u di n g a n y pr oce d ure/ d e vice 
relate d e v e nts, as well as L A A i ma gi n g  (rec o m me n de d 3 -m o nt h a n d 1 2 -m o nt h  L A A i ma gi n g  
fr o m date of i m pla nt) will be c ollecte d a n d re p orte d se parat el y fr o m t he De vice Gr o u p dat a 
a nal yses.  
1 3.  St atistic al C o nsi der ati o ns  
T he f oll o wi n g secti o ns pr o vi de a n o ver vie w of t h e statistical c o nsi derati o ns f or t he O P TI O N 
st u d y.  F urt her details ca n be f o u n d i n t he Statistical A nal ysis Pla n. 
1 3. 1.  E n d p oi nts  
1 3. 1. 1.  Pri m ar y Effic ac y E n d p oi nt  
T he Pri mar y Effi cac y E n d p oi nt is defi ne d as t he Ka pla n Meier esti mate of ti me t o first 
occ urre nce  of str o ke (i ncl u di n g isc he mic a n d/ or h e m orr ha gic), all ca us e deat h, a n d s yste mic 
e m b olis m at 3 6 m o nt hs .  
1 3. 1. 1. 1.  H y p ot heses  
T he o bjecti ve of t h e Pri mar y Effecti ve n ess E n d p oi nt a nal ysis is t o test t he n ull h y p ot hesis 
t hat t he differe nce i n c u m ulati ve i nci de nce bet w ee n t he De vice a n d C o ntr ol gr o u ps is greater 
t ha n a pres p ecifie d n o ni nferi orit y mar gi n .  T h e n ull h y p ot hesis will be teste d vs. t he o ne-
si de d alter nati ve h y p ot hesis t hat t he differe n ce i n c u m ulati ve i nci de nce is l ess t ha n a 
n o ni nferi orit y mar gi n . 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 5 9  of 1 0 2  
 
  
H 0:  S1(t) ≥ S0(t) +  
H a:  S1(t) < S0(t) + , 
W here S
1(t) a n d S0(t) are t he Ka pla n Meier esti mates f or t he c u m ulati ve i nci de nce of str o k e 
(i ncl u di n g isc he mic a n d/ or he m orr ha gi c), all ca us e deat h, a n d s yste mic e m b olis m at 3 6 
m o nt hs  f or t he De vice a n d C o ntr ol gr o u ps, res pecti vel y. 
1 3. 1. 1. 2.  Sa m ple Size  
T h e p o wer a n d sa m ple si ze were  calc ulate d e m pl o yi n g Farri n gt o n Ma n ni n g met h o ds f or n o n -
i nferi orit y usi n g S A S versi o n 9. 4 . T he ass u m pti o ns a n d para m eters pertai ni n g t o t his desi g n 
are as f oll o ws:  
•  P o wer = 8 5. 9 %  
•  Al p ha = 0. 0 2 5 ( o n e -si de d) 
•  E x pecte d De vice a n d C o ntr ol gr o u p perf or ma nce:  c u m ulati ve i nci de nce rate of 1 0 % 
at 3 6 m o nt hs  i n b ot h gr o u ps 
•  A n o ni nferi orit y mar gi n  = 5 %  
•  Attriti o n: c u m ulati ve attriti o n rate of 1 5 % i n t he De vice Gr o u p a n d i n t he C o ntr ol 
g r o u p at 3 6 m o nt hs. 
T he e x pecte d c u m ulati ve i nci de nce of 1 0 % at 3 6 m o nt hs i n t he De vice gr o u p was deri ve d 
fr o m hist orical e ve nt r ates fr o m t he  P R O T E C T A F, C A P, P R E V AI L , a n d C A P 2 st u dies.  
W A T C H M A N  s u bjects wit h pre vi o us a blati o ns fr o m t hese st u dies e x peri e nce d a 1 4. 4 % 
e ve nt at 3 years.  T he c u m ulati ve i nci de nce is e x p ecte d t o be l o w er i n t he O P TI O N st u d y d ue 
t o e n ha nce d  i m pla nt e x p erie nce o ver ti me , de vi ce i m pr o ve me nts , a n d a decreas e d baseli ne 
ris k pr ofile f or s u bjects e nr olle d i n t he O P TI O N st u d y.  T he e x pecte d c u m ulati ve i nci de nce 
i n t he C o ntr ol ar m is e x pecte d t o be e q ual t o t hat of t he De vice ar m. 
T he n o n -i nferi orit y mar gi n of 5 % re prese nts a relati ve ris k of  1. 5.  
Gi ve n t he a b o ve ass u m pti o ns, 1 3 6 0  s u bjects will be re q uir e d. I n or der t o acc o u nt f or u p t o 
1 5 % e x pect e d rat e of attriti o n w hic h i ncl u des s u bjects ra n d o mize d b ut n ot treate d a n d 
s u bjects wit h dra w n or l ost-t o-f oll o w-u p t hr o u g h 3 6 m o nt hs , a t otal of 1 6 0 0  (1 3 6 0 /( 1-0. 1 5 )) 
s u bjects nee d t o be e nr olle d. 
A sa m ple size of 1 6 0 0  s u bjects pr o vi des 8 5. 9 % p o wer f or t he Pri mar y Effecti v e ness 
E n d p oi nt a nal ysis . T heref ore, a m a xi m u m sa m ple size of 1 6 0 0 is deter mi ne d . 
1 3. 1. 1. 3.  Statistical Met h o ds  
T he pri mar y effic ac y e n d p oi nt e ve nt rate fr o m t he W A T C H M A N  F L X D e vice a n d C o ntr ol 
ar ms, S 1(t) a n d S0(t), res pecti vel y, will be esti mate d b y t he Ka pla n Meier m et h o d. T he ti me 
p oi nt of 3 6 m o nt hs is  defi ne d as t he 1 0 9 5 t h da y p ost -ra n d o mizati o n. T he 9 7. 5 % o ne-si de d 
u p per b o u n d of c o nfi de n ce li mit of t he differe nce bet wee n W A T C H M A N  F L X  a n d C o ntr ol 
rates will be calc ulate d usi n g Gree n w o o d f or m ula f or t he vari a nce of t he Ka pla n Meier 
esti mates. T he o bjecti ve is met if t his c o nfi de nce li mit is less t ha n t he pre defi ne d 
n o ni nferi orit y mar gi n of 5 %.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6 0  of 1 0 2  
 
  
If t he n o n-i nf eri orit y h y p ot hesis o bjecti ve is met, a s u peri orit y test will be s u bse q ue ntl y 
perf or m e d a n d a o n e-si de d p-val ue of 0. 0 2 5 will b e c o nsi dere d si g nifica nt.  
1 3. 1. 2.  Pri m ar y S afet y E n d p oi nt  
T he Pri mar y Safet y E n d p oi nt is  Ka pla n Meier esti mate of ti me t o first occ urre nce of n o n -
pr oce d ural blee di n g (I S T H maj or blee di n g a n d cli nicall y rele va nt n o n-maj or blee di n g ) 
t hr o u g h 3 6 m o nt hs. N o n -pr oce d ural e ve nts are t h ose occ urri n g after 3 da ys . 
1 3. 1. 2. 1.  H y p ot heses  
T he o bjecti ve of t h e Pri mar y Safet y E n d p oi nt a n al ysis is t o test t he n ull h y p ot hesis t hat  ti me-
t o-e ve nt distri b uti o ns d o n ot differ bet w ee n t he De vice a n d C o ntr ol gr o u ps.  T he n ull 
h y p ot hesis will be teste d vs. t he 2 -si de d alter nati ve h y p ot hesis t hat t he ti me-t o-e ve nt c ur ves 
are differe nt.  
H 0:  S1(t) = S0(t) 
H a:  S1(t) ≠ S0(t), 
W here S
1(t) a n d S0(t) are t he ti me-t o-e ve nt c ur ves f or I S T H maj or blee di n g a n d cli nicall y 
rele va nt n o n-m aj or blee di n g  of  t he De vice  a n d C o ntr ol gr o u ps, res pecti vel y . 
1 3. 1. 2. 2.  Sa m ple Size  
T his sa m ple size was cal c ulate d e m pl o yi n g l o g ra n k test met h o d ol o g y usi n g E A S T 6 
s oft ware wit h t he f oll o wi n g ass u m pti o ns:  
•  E x pecte d e v e nt rate of t h e De vice gr o u p = 1 4 % a n d of t he C o ntr ol gr o u p = 2 0 %  
•  2 -si de d al p ha = 5 % 
•  P o wer = 8 6. 4 %  
•  E x pecte d attriti o n rat e = 2 0 %  
•  Re q uire d sa m ple size = 1 6 0 0 s u bjects 
T he e x pecte d Pri mar y Safet y E n d p oi nt e ve nt rat e i n t he De vice gr o u p is bas e d off t he 
c o m bi ne d P R O T E C T A F, C A P, P R E V AI L, a n d C A P 2 W A T C H M A N ar ms.   T he 
o bser ve d rate of n o n -pr oce d ural maj or blee di n g at 3 6 m o nt hs i n t hese s u bjects was 
9. 4 %.  T he Pri mar y Safet y E n d p oi nt e ve nt rate i n t he O P TI O N De vice gr o u p is t he n 
e x pecte d t o b e 1 4 %, w hi c h acc o u nts f or si milar n o n -pr oce d ural maj or blee di n g ris k as 
i n pre vi o us W A T C H M A N st u dies b ut wit h t he a d diti o n of cli nicall y rele va nt n o n-
maj or blee ds u nrel ate d t o t he i m pla n t pr oce d ure.  T he e x pecte d rate of 2 0 % i n t he 
C o ntr ol gr o u p is base d off t he rates of maj or or cli nicall y rele va nt n o n -maj or blee ds 
re p orte d i n t he A RI S T O T L E, E N G A G E, a n d R O C K E T-A F st u dies .   
I n or der t o acc o u nt f or u p t o 2 0 % e x pecte d rate of attriti o n w hic h i ncl u des s u bjects 
w h o die, wit h dra w,  or  are l ost-t o-f oll o w-u p t hr o u g h 3 6 m o nt hs  wit h o ut e x perie nci n g 
a n e n d p oi nt e ve nt , a t otal of 16 0 0 ( 1 2 8 0 /( 1-0. 2 )) s u bjects nee d t o be e nr olle d. A 
sa m ple size of 1 6 0 0 s u bj ects pr o vi des a p pr o xi matel y 8 6. 4 % p o wer f or t he Pri mar y 
Safet y  E n d p oi nt a nal ysis . 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6 1  of 1 0 2  
 
  
1 3. 1. 2. 3.  Statistical Met h o ds  
All s u bjects i n t he ra n d o mize d c o h ort will be i ncl u de d i n t he a nal ysis. L o g - ra n k test will be 
perf or me d i n cl u di n g all s u bjects i n data base at t he ti me of a nal ysis p ost 3 6 m o nt hs. T he 
o bjecti ve is met if p -val u e of t he l o g -ra n k test is less t ha n 0. 0 5. 
1 3. 1. 3.  Sec o n d ar y  E n d p oi nt  
T he Sec o n d ar y E n d p oi nt is  t he Ka pla n Meier esti mate of ti me t o first occ urre nce of all I S T H 
maj or blee di n g  at 3 6 m o nt hs . 
1 3. 1. 3. 1.  H y p ot heses  
T he o bjecti ve of t h e Sec o n dar y  E n d p oi nt a nal ysis is t o test t he n ull h y p ot hesis t hat f or t he 
differe n ce i n c u m ulati ve i nci de nce b et wee n t he De vice a n d C o ntr ol gr o u ps is greater t ha n a 
pres pecifi e d n o ni nferi orit y mar gi n .  T he n ull h y p ot hesis will be teste d vs. t he o ne-si de d 
alter nati ve h y p ot hesis t hat t he differe n ce i n c u m ul ati ve i nci de nce is less t ha n a n o ni nferi orit y 
mar gi n . 
H 0:  S1(t) ≥ S0(t) +  
H a:  S1(t) < S0(t) + , 
W here S
1(t) a n d S0(t) are t he Ka pla n Meier esti mates f or c u m ulati ve i nci de nce of all I S T H 
maj or blee di n g  at 3 6 m o nt hs  f or t he De vice a n d C o ntr ol gr o u ps, res pecti v el y. 
1 3. 1. 3. 2.  Sa m ple Size  
T h e p o wer a n d sa m ple si ze were  calc ulate d e m pl o yi n g Farri n gt o n Ma n ni n g met h o ds f or n o n -
i nferi orit y usi n g S A S versi o n 9. 4 . T he ass u m pti o ns a n d para m eters pertai ni n g t o t his desi g n 
are as f oll o ws:  
•  P o wer = 8 4. 3 %  
•  Al p ha =  0. 0 2 5 ( o n e -si de d) 
•  E x pecte d De vice a n d C o ntr ol gr o u p perf or ma nce:  c u m ulati ve i nci de nce of 1 1 % at 3 6 
m o nt hs  i n b ot h gr o u ps 
•  A n o ni nferi orit y mar gi n  = 5. 2 5 %  
•  Attriti o n: c u m ulati ve attriti o n rate of 2 0 % i n t he De vice Gr o u p a n d i n t he C o ntr ol 
Gr o u p at 3 6 m o nt hs.  
T he e x pecte d de vic e ti me -t o-e v e nt rate of 1 1 % at 3 6 m o nt hs w as deri ve d fr o m s u bjects wit h 
pre vi o us a blati o ns fr o m t he c o m bi ne d P R O T E C T A F, C A P, P R E V AI L, a n d C A P 2 
W A T C H M A N ar ms.  T he o bser ve d e ve nt r ate i n t hese s u bjects w as 1 3. 6 % e ve nt at 3 years.  
T his rate is e x pecte d t o b e l o wer i n t he O P TI O N de vice ar m d ue t o e n ha n ce d i m pla nt 
e x perie n ce o ver ti me, de vice i m pr o ve me nts, a n d t he use of D O A Cs p ost-i m pla nt rat her t ha n 
Warfari n.  T he e x pecte d e ve nt rate i n t he C o ntr ol gr o u p is e x pecte d t o b e si milar t o t hat o f 
t he De vice gr o u p.  T he n o n -i nferi orit y mar gi n of 5. 2 5 % re prese nts a relati ve ris k of 1. 4 8. 

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6 2  of 1 0 2  
 
  
Gi ve n t he a b o ve ass u m pti o ns, 1 2 8 0  s u bjects will be re q uir e d. I n or der t o acc o u nt f or u p t o 
2 0 % e x pect e d rat e of attriti o n w hic h i ncl u des s u bjects w h o die,  wit h dra w  or  are l ost-t o-
f oll o w-u p t hr o u g h 3 6 m o nt hs wit h o ut e x perie nci n g a n e n d p oi nt e ve nt, a t ot al of 1 6 00 
( 1 28 0 /( 1-0. 2 )) s u bjects n ee d t o be e nr olle d. 
A sa m ple size of 1 6 0 0  s u bjects pr o vi des a p pr o xi m atel y 84 % p o wer f or t he Sec o n d ar y 
E n d p oi nt a nal ysis .  
1 3. 1. 3. 3.  Statistical Met h o ds  
All s u bjects i n t he ra n d o mize d c o h ort will be i ncl u de d i n t he a nal ysis. T he sec o n d ar y 
e n d p oi nt e ve nt fr o m t he Watc h ma n d e vice a n d c o ntr ol ar ms, S 1(t) a n d S0(t) at 3 6 m o nt hs, 
defi ne d as t he 1 0 9 5 t h da y p ost -ra n d o mizati o n, will be esti mate d b y t he Ka pl a n Meier met h o d. 
T he 9 7. 5 % o ne -si de d u p per b o u n d of c o nfi de nce li mit of t he differe nce bet wee n 
W A T C H M A N  F L X a n d C o ntr ol rates at 3 6 m o nt hs will be calc ulate d usi n g Gree n w o o d 
f or m ula f or t he v aria n ce of t he Ka pla n M eier esti mates. T he o bjecti ve is met if t his 
c o nfi de nce li mit is less t ha n t he pre d efi ne d n o ni nf eri orit y mar gi n of 5.2 5 %.  
 
If t he n o n-i nf eri orit y h y p ot hesis o bjecti ve is met, a s u peri orit y test will be s u bse q ue ntl y 
perf or me d  a n d a o n e-si de d p-val ue of 0. 0 2 5 will b e c o nsi dere d si g nifica nt.  
1 3. 2.  Ge ner al St atistic al Met h o ds  
1 3. 2. 1.  A n al ysis Sets  
T he pri mar y a n al ysis f or eac h of t h e Pri mar y a n d Sec o n dar y  E n d p oi nts will be perf or m e d o n 
a n i nte nt -t o-treat b asis, wit h eac h s u bject a n al yze d as bei n g part of t heir  ra n d o mize d gr o u p 
re gar dl ess of t he act ual tr eat me nt recei ve d. A d diti o nal a nal ysis sets per act ual treat me nt  
recei v e d will be perf or m e d  f or t he Pri mar y a n d Sec o n dar y  E n d p oi nt s as se nsiti vit y a nal yses.  
1 3. 2. 2.  C o ntr ol of S yste m atic Err or/ Bi as  
Selecti o n of s u bjects f or e nr oll me nt will be ma de fr o m t he I n vesti gat or’s us ual s u bject l oa d. 
All s u bjects meeti n g t he eli gi bilit y criteria a n d ha vi n g si g ne d t he I C F will be eli gi ble f or 
e nr oll me nt i n t he st u d y.  T o c o ntr ol f or t he p ote nti al bias t hat c o ul d be i ntr o d uce d via s p o ns or 
classificati o n of a d v erse e ve nts, a  Cli nical E ve nts C o m mittee ( C E C) will a dj u dicate all maj or  
e ve nts t o be use d i n t he d ata a nal yses.  
1 3. 2. 3.  N u m ber of S u bjects per I n vesti g ati ve Site  
T o a v oi d a n y site effect a n d bias, n o  site will be a ut h orize d t o i m pla nt or atte m pt m ore t ha n 
1 5 % of t he 1 6 0 0 ra n d o mize d s u bjects  ( n = 2 4 0 ) per t his pr ot oc ol wit h o ut  pri or a p pr o val fr o m 
t he s p o ns or.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6 3  of 1 0 2  
 
  
1 3. 3.  D at a A n alyses  
1 3. 3. 1.  Descri pti o n of B aseli ne V ari a bles  
Baseli ne de m o gra p hic a n d cli nical varia bles will be s u m marize d f or eac h of t he treat me nt 
gr o u ps f or b ot h t he i nte n t-t o-treat a n d p er pr ot o c ol  p o p ulati o ns. All c o nti n u o us varia bles will 
be s u m marize d as mea ns, me dia ns, sta n dar d de vi ati o ns a n d i nter q uartile ra n ges a n d 
c o m pare d b et wee n treat me nt gr o u ps usi n g o ne -wa y a nal ysis of varia nce ( A N O V A) or t he 
n o n -para m etric Kr us k al -Wallis test.  Cate g orical varia bles will be s u m marize d as fre q ue n cies 
a n d perce nta ges a n d c o m pare d bet w ee n tr eat me nt gr o u ps usi n g Pears o n’ s 2 test or Fis her’s 
e xact test, as a p pr o priat e.   Or di nal varia bl es will be c o m pare d usi n g C oc hra n -Ma ntel -
Hae nszel test wit h r o w mea n sc ores.  
 
A b y -s u bject listi n g of ke y de m o gra p hic dat a a n d baseli ne c haracteristics, i ncl u di n g varia bles 
use d f or stratificati o n will be prese nte d.  
1 3. 3. 2.  A d diti o n al E n d p oi nts/ Me as ure me nts  
1.  T he occ urre n ce a n d i n ci de nce of:  
•  Str o ke  
o  Is c he mic str o ke 
o  He m orr ha gi c str o ke  
o  Disa bli n g str o ke  
o  N o n -disa bli n g str o ke  
•  S yste mic e m b olis m  
•  Pr oce d ural a n d n o n -pr oce d ural blee di n g  a n d classificati o ns (i.e., maj or blee di n g per 
I S T H; a n d cli nicall y rele va nt n o n-maj or blee di n g)  
•  All -ca use d eat h  
•  Car di o vasc ular/ u n k n o w n deat h  
•  N o n -car di o vasc ular deat h  
•  De vice relate d T hr o m b us  
2.  Pr oce d ural s u ccess  
3.  Rate s of effecti ve  ( defi ne d as jet size of ≤5 m m) a n d c o m plete ( defi ne d as n o peri -de vice 
fl o w) L A A cl os ure at 3 - a n d 1 2-m o nt hs  p ost i m pla nt  
4.  Free d o m fr o m A F  
Cli nical rec urre nces of atrial fi brillati o n are defi ne d as a n y o f t he f oll o wi n g: 
•  D oc u me nte d atri al fi brillati o n  e pis o de, or ne w o ns et of atrial fl utter or atrial 
tac h ycar dia e v e nt ( ≥ 3 0 s ec o n ds i n d urati o n or fr o m a 1 0 sec o n d 1 2-lea d E K G) p ost -
ra n d o mizati o n or i n de x pr oce d ure , w hic h e ver is later a n d t he e n d of st u d y. 
•  A n y of t he f oll o wi n g i nter ve nti o ns f or atrial fi brillati o n, or ne w o nset of atrial fl utter 
or atrial tac h y car di a p ost -ra n d o mizati o n or i n de x pr oce d ure, w hic h e ver is l ater a n d 
t he e n d of st u d y: 
o  Re peat a blati o n pr oce d ure  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 6 4  of 1 0 2  
 
  
o  Electrical  a n d/ or p har mac ol o gical car di o versi o n f or A F/ A F L/ A T  
•  Prescri be d a hi g h er d ose of a n y  A A D  f or atri al arr h yt h mias d oc u me nte d at baseli ne  
•  Prescri be d a n e w A A D  f or atrial arr h yt h mias n ot d oc u me nte d at bas eli ne  
•  Fail ure t o disc o nti n ue A A D bet wee n 9 1 da ys a n d e n d of st u d y p ost a blati o n 
pr oce d ure  
5.  Healt hcare res o urce utilizati o n  
6.  Q ualit y of life  
1 3. 3. 3.  S u b gr o u p A n al yses  
P er st u d y desi g n, t he f oll o wi n g s u b gr o u ps will be a nal yze d f or t he Pri mar y E n d p oi nts wit hi n 
t he st u d y: 
•  Se q ue ntial vs. C o nc o mita nt  
•  Se x ( Fe m ale vs. Male)  
•  A ge at ti me of c o ns e nt ( < 7 5 years vs. ≥ 7 5  years)  
•  Str o ke r is k ( C H A2D S 2-V A Sc Sc ore)  
•  Blee di n g ris k ( H A S -B L E D Sc ore)  
•  A F t y pe  
Ti me -t o-e ve nt c ur ves will be c o nstr ucte d f or eac h treat me nt gr o u p, H Rs a n d l o g ra n k test p -
val ues will be calc ul ate d wit hi n eac h s u b gr o u p, a n d s u b gr o u p b y treat me nt i nteracti o ns will 
be teste d usi n g C o x re gressi o n. P -val ues will be pr o vi de d wit h o ut m ulti plicit y a dj ust me nts . 
 
I n a d diti o n, healt h care utilizati o n will be c o m pare d bet wee n C o nc o mita nt a n d S e q ue ntial  
gr o u ps . 
1 3. 3. 4.  J ustific ati o n of P o oli n g  
P o ola bilit y will be assesse d acr oss site, g e o gra p hi cal re gi o n, a n d s e q ue ntial vs. c o nc o mita nt 
a blati o n f or eac h pri mar y e n d p oi nt.  Res ults will als o be prese nte d se paratel y f or site, 
ge o gra p hic al re gi o n, a n d se q ue ntial vs. c o nc o mita nt a blati o ns re gar dless of t he res ults of t he 
p o ola bilit y assess me nts.  Sites t hat s uccessf ull y i m pla nte d wit h 5 s u bjects or fe wer will be 
c o nsi dere d “s mall sites” a n d will be gr o u pe d t o get her as o ne site  p er  ge o gra p hical re gi o n  f or 
t he p ur p ose of p o ola bilit y assess me nt. 
1 3. 3. 4. 1.  P o oli n g of I n vesti gati o nal Ce nters  
Ce nter -t o-ce nter h eter o g e neit y will be assesse d f or t he Pri mar y a n d Sec o n d ar y  en d p oi nt s 
usi n g a s hare d frailt y m o del.  Ti me t o e ve nt varia bles  will be m o delle d o n ra n d o mize d 
treat me nt gr o u p, wit h i n v esti gati o nal ce nter i ncl u d e d as a ra n d o m effect wit h a l o g n or mal 
distri b uti o n. Ce nters will be dee me d heter o g e ne o us wit h res pect t o t he Pri mar y Effecti ve n ess 
E n d p oi nt if t he p -val ue fr o m Wal d test f o r t he i n vesti gati o nal ce nter ra n d o m effect is < 0. 1 5.   

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1 3. 3. 5.  M ulti v ari a ble A n al yses  
M ulti varia ble a nal ysis, s uc h as C O X re gressi o n a nal ysis wit h c o variate a dj ust me nt, will be 
perf or me d i n li g ht of e vi de nce t hat ra n d o mizati o n di d n ot res ult i n bala nce treat me nt gr o u ps, 
acc or di n g t o bas eli ne C H A D S 2 or C H A 2D S 2-V A Sc sc ores . T h ese a n al yses will be perf or me d 
as a ncillar y t o t he pri mar y e n d p oi nt a nal yses.  
1 3. 3. 6.  Se nsiti vit y A n al yses f or t he Pri m ar y E n d p oi nts  
Per Ka pla n -M eier met h o d, s u bjects w h o c o u nt t o war ds attriti o n will still c o ntri b ute t o war ds 
t he pri mar y effecti ve ness e n d p oi nt e ve nt rates u ntil t he ti me at w hic h t he y are l ost t o f oll o w-
u p ( i.e., ce ns ore d). Se nsiti vit y a nal yses will be perf or me d acc or di n g t o t he f oll o wi n g:  
Re gar di n g attriti o n bias, baseli ne c haracteristics will be c o m pare d acr oss attriti o n vs n o n -
attriti o n s u bjects f or eac h pri mar y e n d p oi nt t o deter mi ne if s u bjects c o u nte d t o war ds attriti o n 
ha d a hi g her b aseli ne ris k pr ofile.  I n a d diti o n, ti p pi n g -p oi nt a nal ysis will be c o n d ucte d t o 
deter mi ne t he l o west/ hi g hest ass u me d rate i n attriti o n s u bjects (ass u mi n g t he y ha d bee n 
f oll o we d f or 3 -y ears) s uc h t hat t he alter nati ve h y p ot hesis  is n o l o n ger met/faile d.  T he 
pr o ba bilit y of o bser vi n g t his ti p pi n g -p oi nt rate i n t he attriti o n s u bjects (ass u mi n g a tr ue rate 
e q ual t o t hat o bser ve d i n n o n -attriti o n s u bjects) will t he n be calc ulate d t o d eter mi ne t he 
li keli h o o d of o bser vi n g t his ti p pi n g-p oi nt rate i n t he attriti o n s u bjects.   
1 3. 3. 7.  Missi n g D at a  
E ver y eff ort will be u n derta ke n t o mi ni mize missi n g data.  I n ti me -t o-e v e nt o utc o mes dr o p -
o uts will be ce ns ore d at t he ti me of last f oll o w -u p, c o nsiste nt wit h t he Ka pla n -Meier 
met h o d ol o g y.  T he last f oll o w -u p date will be t he latest of t he f oll o wi n g dates f or eac h 
s u bject: date of a d v erse e ve nt, ra n d o mizati o n date, i m pla nt pr oce d ure d ate, disc har ge d ate, 
a n d f oll o w-u p visit date.   U nless ot her wise s pecifi e d, n o statistical tec h ni q ues will be use d t o 
i m p ute missi n g data f or c o nti n u o us or cate g orical o utc o mes.  T he n u m ber of s u bjects 
i ncl u de d i n eac h a nal ysis will be re p orte d s o t hat t he re vie wer ca n ass ess t he p ote ntial i m pact 
of m issi n g data. 
 
F or eac h pri mar y  a n d sec o n dar y  e n d p oi nt, a se nsiti vit y a nal ysis will be c o n d ucte d t o assess 
t he i m pact of ce ns ore d d ata a n d will i ncl u de a w orst-case a nal ysis.  
1 3. 3. 8.  Ot her A n al yses  
Q u alit y of Life  
Cli nical trials i ncreasi n gl y rec o g nize t he val ue of i ncl u di n g patie nt re p orte d o utc o me 
meas ures i n t heir d esi g n. T o u n dersta n d t he i m pact of atrial fi brillati o n relat e d pr oce d ures 
a n d disease ma n a ge me nt o n patie nt’s q ualit y of life, t he q ualit y -of -life i nstr u me nts use d f or 
t he trial will be t he E Q-5 D -5 L a n d t he 1 2 -Ite m S h ort F or m Healt h S ur ve y ( S F-1 2) f or 
ge neric i nstr u me nts. T he E Q -5 D is a des cri pti ve s yste m of healt h -relate d q ualit y of life states 
c o nsisti n g of fi ve di me nsi o ns ( m o bilit y, self -care, us ual acti vities, pai n/ disc o mf ort, 

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a n xiet y/ de pressi o n) eac h of w hic h ca n t a ke o ne of fi ve res p o nses. T he res p o nses rec or d fi ve 
le vels of se verit y ( n o pr o ble ms/sli g ht pr o ble ms/ m o derate pr o ble ms/se vere pr o ble ms/e xtre me 
pr o ble ms) wit hi n a partic ular E Q -5 D di me nsi o n. T he S F -1 2 i ncl u des 1 2 di me n si o ns wit h 
var yi n g le vels of res p o ns e. S u bjects will be as ke d t o c o m plete t he q uesti o n naires at t he 
e nr oll me nt visit as well as at t he 1 2 - a n d 3 6-m o nt h f oll o w -u p visit.   
Ot her data a nal yses a n d res ults n ot e n u merate d i n t he pr ot oc ol will be descri be d i n t he 
Statistical A nal ysis Pla n.  
1 3. 3. 9.  I nteri m A n al yses  
N o f or mal i nteri m a nal ys es are pl a n ne d f or t he p ur p ose of st o p pi n g t his st u d y earl y f or 
declari n g effecti ve ness or f or f utilit y.  
1 3. 3. 1 0.  C h a n ges t o Pl a n ne d A n al yses  
A n y c ha n ges t o t he pla n n e d statistical a nal yses ma de pri or t o perf or mi n g t he a nal yses  will be 
d oc u me nte d i n a n a m e n d e d Statistical A nal ysis Pla n a p pr o ve d pri or t o  perf or mi n g t he 
a nal yses. C ha n ges fr o m t he pla n ne d statistical met h o ds after perf or mi n g t he a nal yses  will be 
d oc u me nte d i n t he cli nic al st u d y re p ort al o n g wit h a reas o n f or t he de viati o n . 
1 4.  He alt h Ec o n o mics O utc o mes  
A f or mal he alt h ec o n o mi cs a nal ysis ma y be c o m pl ete d as part of t his trial st u d y, gi ve n 
mea ni n gf ul cli nical res ults are o btai ne d. T his will t a ke i nt o c o nsi derati o n a n y differe n ces i n 
s ur vi val, c o m plicati o n rates, q ualit y of life, a n d res o urce utilizati o n. T he E Q -5 D a n d  S F -1 2 
ma y be use d t o assess h ealt h utilities. We will ca pt ure healt h care utilizati o n meas ures at all 
sites. T hese i n p uts ma y be use d i n healt h ec o n o mics a nal ysis perf or me d.  
1 5.  D at a M a n a ge me nt  
1 5. 1.  D at a C ollecti o n, Pr ocessi n g, a n d Revie w  
S u bject data will be rec or de d i n a li mite d access s ec ure el ectr o nic d ata ca pt ure ( E D C) 
s yste m.  
 
T he cli nical data b ase will resi de o n a pr o d u cti o n ser ver h oste d b y iMe di dat a E D C S yste m . 
All c ha n ges ma de t o t he cli nical data will be ca pt ure d i n a n electr o nic a u dit trail a n d 
a vaila ble f or re vie w b y t he s p o ns or or its re prese ntati ve. T he ass ociat e d R a ve s oft ware a n d 
data base h a ve bee n desi g ne d t o meet re g ulat or y c o m plia nce f or d e pl o y me nt as part of a 
vali date d s yste m c o m plia nt wit h la ws a n d re g ulati o ns a p plica ble t o t he c o n d uct of cli nical 
st u dies pertai ni n g t o t he use of ele ctr o nic rec or ds a n d si g nat ures. Data base bac k u ps are 
perf or me d re g ularl y.  
 

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T he I n vesti gat or pr o vi d es his/ her electr o nic si g nat ure o n t he a p pr o priate electr o nic cas e 
re p ort f or ms (e C R Fs) i n c o m plia nce wit h l ocal r e g ulati o ns. A writte n si g nat ure o n pri nt o uts 
of t he e C R Fs m ust als o be pr o vi de d if re q uire d b y l ocal re g ulati o n. C ha n ge s t o data 
pre vi o usl y s u b mitte d t o t he s p o ns or re q uir e a n e w electr o nic si g nat ure b y t he I n vesti gat or 
ac k n o wle d gi n g a n d a p pr o vi n g t he c ha n ges.  
 
Vis ual a n d/ or ele ctr o nic data re vie w will be perf or me d t o i de ntif y p ossi ble data 
discre pa n cies. Ma n ual a n d/ or a ut o matic q ueries will be creat e d i n t he Me di data E D C s yste m 
a n d will be iss ue d t o t he site f or a p pr o priate res p o nse. Site staff will be res p o nsi ble f or 
res ol vi n g all q ueries i n t h e data bas e. 
 
All access t o t he cli nical data base will be c ha n ge d t o “ Rea d o nl y” after all data is eit her 
“ Har d L o c ke d ” or “ E ntr y L oc ke d .” O nce acce pta nce of t he fi nal re p ort or fi nalizati o n of 
p u blicati o ns (as a p plica bl e) is recei ve d, fi n al data b ase st ora ge a n d arc hi vi n g acti vities ca n 
be gi n. O nce all of t he cl ose o ut acti vities are c o m plete d , a re q uest t o I T is s u b mitte d t o ha ve 
t he “ Data b ase L o c ke d” or Dec o m missi o ne d a n d all data base access re v o k e d. 
1 5. 2.  D at a Rete nti o n  
T he Pri nci pal I n vesti gat or or his/ her desi g ne e or I n vesti gati o nal site will mai ntai n  all 
esse ntial st u d y d oc u me nts a n d s o urce d o c u me ntati o n t hat s u p p ort t he data c ollecte d o n t he 
st u d y s u bjects i n c o m plia nce wit h a p plica bl e re g ul at or y re q uir e me nts .   
T he Pri nci pal I n vesti gat or or his/ her desi g ne e will ta ke meas ures t o pre v e nt acci de nt al or 
pre mat ure d estr ucti o n of t hese d oc u me nts . If f or a n y reas o n t he Pri nci pal I n vesti gat or or 
his/ her desi g nee wit h dr a ws res p o nsi bilit y f or mai ntai ni n g t hese esse ntial d oc u me nts, c ust o d y 
m ust be tra nsferre d t o a n i n di vi d ual w h o will ass u me res p o nsi bilit y a n d B S C m ust recei ve 
writte n n otificati o n of t his c ust o dial c ha n ge. Sites are re q uire d t o i nf or m B ost o n Scie ntific i n 
writi n g w here p a per or el ectr o nic files are mai ntai n e d i n case files are st ore d off site a n d are 
n ot rea dil y a vaila ble.  
1 5. 3.  C ore L a b or at ories  
A n i n de pe n de nt c ore la b orat or y will be utilize d t o re vie w L A A i ma gi n g c ollecte d at pr ot oc ol 
re q uire d ti me p oi nts d uri n g t he st u d y. All i nter pretati o ns of L A A i ma gi n g f or p ur p oses of 
s u bject care will be c o n d ucte d b y eac h site’s i n vesti gat or a n d/ or Ec h ocar di o gra p her. T h e 
C ore La b will n ot be utilize d as a m ea ns of refere n ce f or s u bject ma na g e me nt decisi o ns.  
L A A ima gi n g fr o m  pre -pla n ni n g i ma ges f or I C E g ui de d i m pla nts, i m pla nt, 3-m o nt hs, a n d 
1 2 -m o nt hs  will be c ollecte d b y eac h st u d y site acc or di n g t o t he I m a gi n g Ma n ual a n d 
s u b mitte d t o t he C ore La b f or re vie w. T he C ore L a b will pr o vi de t he s p o ns or wit h s u m mar y 
of res ults f or re p orti n g p ur p oses.  

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1 6.  De vi ati o ns  
A n I n vesti gat or m ust n ot ma ke a n y c h a n ges or de viate fr o m t his pr ot oc ol , e xce pt t o pr otect 
t he life a n d p h ysical w ell-bei n g of a s u bject i n a n e mer ge n c y. A n i n vesti gat or s hall n otif y t he 
s p o ns or a n d t he re vi e wi n g I R B/ EC / R E B a n d t he re g ulat or y a ut h orit y if a p plica ble  of a n y 
de viati o n fr o m t he i n vesti gati o nal pla n t o pr otect t he life or p h ysical w ell -b ei n g of a s u bject 
i n a n e mer ge n c y, a n d t h ose de viati o ns w hic h affect t he scie ntific i nte grit y of t he cli nical 
i n vesti gati o n. S uc h n otice s hall be gi ve n as s o o n as p ossi ble, b ut n o later t ha n 5  w or ki n g da ys 
after t he e mer g e nc y occ urre d, or p er pre vaili n g l ocal re q uir e me nts, if s o o ner t ha n 5  w or ki n g 
da ys.  
All de viati o ns fr o m t he i n vesti gati o nal pla n, wit h t he reas o n f or t he de vi ati o n a n d t he date of 
occ urre nce, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or  usi n g E D C.  Sites  ma y als o be 
re q uire d t o r e p ort de viati o ns t o t he I R B/ E C/ R E B, a n d t he re g ulat or y a ut h orit y, per l ocal 
g ui deli nes a n d nati o nal/ g o ver n me nt re g ul ati o ns.  
De viati o ns will be re vie we d a n d e v al uate d o n a n o n g oi n g basis a n d, as necessar y, a p pr o priate 
c orrecti ve a n d pre ve nti ve acti o ns (i ncl u di n g I R B/ E C/ R E B/Re g ulat or y A ut h orit y/ F D A  
n otificati o n, site re-trai ni n g, or site disc o nti n uati o n /ter mi nati o n) will be p ut i nt o place b y t he 
s p o ns or. 
1 7.  De vice/ E q ui p me nt Acc o u nt a bilit y  
1 7. 1.  C o m merci al E q ui p me nt  
T he c o m merciall y a p pr o ve d W A T C H M A N Access S yste m  ma y be use d i n all ge o gra p hies.  
T he W A T C H M A N Tr u Seal 
Access S yste m will be use d i n all ge o gra p hies  i n w hic h it is 
c o m merciall y a p pr o ve d .  W he n p ossi ble, t h e W A T C H M A N Tr u S eal Access S yste m s h o ul d be 
use d.   I n v esti gat ors s h o ul d ha ve e x peri e nce usi n g t he 
W A T C H M A N F L X De vice a n d/ or 
Tr u Seal Access S yste m, pri or t o utilizi n g t he m t o get her i n t he trial.   
 
I n g e o gra p hi es w here t he C E mar k  a p plies, a n d ot her a p plica bl e ge o gra p hi es,  t he c o m mercial 
W A T C H M A N F L X D e vice a n d D eli ver y s yste m will be utilize d u n der t he O P TI O N  
c o m mercial directi o ns f or use  wit h t he a d diti o nal re q uire me nt of a 1 2 -m o nt h L A A i ma gi n g  
e xa mi nati o n .   T his ali g ns wit h the O P TI O N IF U w hic h is use d i n ge o gra p hies w here t h e C E 
mar k  d oes n ot a p pl y . 
 
If a d diti o nal W A T C H M A N Access S yste ms ge nerati o n(s) b ec o me  c o m merciall y  a v aila ble 
d uri n g t he e nr oll me nt p h ase of t he st u d y, t hese Access S yste ms ma y  be use d i n O P TI O N . 
1 7. 2.  I nvesti g ati o n al E q ui p me nt 
I n g e o gra p hi es w here W A T C H M A N F L X ma y n ot be c o m merciall y a vaila ble , t he 
W A T C H M A N F L X D e vice a n d D eli ver y S yste m is la bele d as i n vesti gati o nal a n d will be 
utilize d u n der t he sa me O P TI O N i n vesti gati o nal directi o ns f or use.      

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T he i n vesti gati o nal de vices/e q ui p me nt s hall be sec urel y mai ntai ne d, c o ntr olle d, a n d use d 
o nl y i n t his cli nical st u d y .  T he s p o ns or s hall kee p rec or ds t o d oc u me nt t he p h ysical l ocati o n 
of all i n vesti gati o nal de vices / e q ui p me nt fr o m s hi p me nt of i n vesti gati o nal de vices fr o m B S C 
or desi g nate d facilit y /e q ui p me nt t o t he i n vesti gati o n sites u ntil ret ur n or dis p osal.  E q ui p me nt 
s hall be ret ur ne d i n t he c o n diti o n i n w hic h it was pr o vi de d, reas o na ble wear a n d tear 
e xce pte d.  
 
Rec or ds s hall be ke pt b y i n vesti gati o nal site t o d oc u me nt t he p h ysical l ocati o n a n d c o n diti o ns 
of st ora ge of all i n vesti gati o nal de vices/e q ui p me nt.  
T he pri nci pal i n vesti gat or or a n a ut h ori ze d desi g n ee s hall kee p rec or ds d oc u me nti n g t he 
recei pt, use, ret ur n a n d dis p osal of t he i n vesti gati o nal de vices/e q ui p me nt, w hic h s hall i ncl u de 
t he f oll o wi n g: 
•  Date of recei pt  
•  I d e ntificati o n of eac h i n v esti gati o nal de vice/ piece of e q ui p me nt ( batc h n u m ber or u ni q ue 
c o de)  
•  E x pir y date, as a p plica bl e  
•  Date or dat es of use  
•  S u bject i de ntificati o n  
•  Date o n w hic h t he i n v esti gati o nal de vice/ piece of e q ui p me nt was ret ur n e d/ e x pla nte d fr o m 
s u bject, if a p plica ble 
•  Date of ret ur n (a n d n u m ber) of u n us e d, e x pir e d, or malf u ncti o ni n g i n vesti gati o nal 
de vices/e q ui p me nt, if a p plica ble.  
1 8.  C o m pli a nce  
1 8. 1.  St ate me nt of C o m pli a nce  
T his cli nical i n vesti gati o n is fi na nce d b y t he st u d y s p o ns or. Bef ore t he i n v esti gati o nal site 
ca n be “ A ut h orize d t o E nr oll,” t he i n vesti gati o nal site m ust e nter i nt o a Cli nical St u d y 
A gree me nt wit h t he s p o ns or t hat details t he fi na nci n g of t he st u d y as wel l as t he ri g hts a n d 
o bli gati o ns of t he i n vesti gati o nal site a n d t he i n vesti gat or.  
 
T his st u d y will be c o n d ucte d i n acc or da n ce wit h  2 1 C F R part 5 6, part 5 0 , p art 5 4 a n d part 
8 1 2, E N I S O 1 4 1 5 5 Cli nical I n vesti gati o n of Me di cal De vices f or H u ma n S u bjects, rele va nt 
parts of t he I C H G ui d eli nes f or G o o d Cli nical Practice , et hical pri nci ples t h at ha ve t heir 
ori gi ns i n t he Declarati o n of Helsi n ki, a n d a p plica ble i n di vi d ual c o u ntr y la ws a n d 
re g ulati o ns. T he st u d y s hall n ot be gi n u ntil t he re q uire d a p pr o val/fa v ora ble o pi ni o n fr o m t he 
I R B/ E C/ R E B a n d/ or re g ulat or y a ut h orit y has bee n o btai ne d, if a p pr o pri ate. Als o, t he st u d y 
s hall n ot be gi n pri or t o iss ua nce of t h e site A ut h orizati o n t o E nr oll, as pr o vi de d b y t he 
s p o ns or. A n y a d diti o nal re q uire me nts i m p ose d b y t he I R B/ E C / R E B or re g ulat or y a ut h orit y 
s hall be f oll o we d, if a p pr o priate.  

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1 8. 2.  I nvesti g at or Res p o nsi bilities 
T he Pri nci pal I n vesti gat or of a n i n vesti gati o nal site is res p o nsi ble f or e ns uri n g t hat t he st u d y 
is c o n d ucte d i n acc or da n ce wit h t he Cli nical St u d y A gree me nt, t he cli nical i n vesti gati o n 
pla n, I S O 1 4 1 5 5, et hical pri nci ples t hat ha ve t heir ori gi ns i n t he Declarati o n of Helsi n ki, a n y 
c o n diti o ns of a p pr o val i m p ose d b y t he re vie wi n g I R B/ E C / R E B, a n d pre vaili n g l ocal a n d/ or 
c o u ntr y la ws a n d/ or re g ulati o ns, w hic he ver aff or ds t he greater pr otecti o n t o t he s u bject.  
T he Pri nci pal I n vesti gat or’s res p o nsi bilities i ncl u de, b ut are n ot li mite d t o, t he f oll o wi n g.  
•  Pri or t o be gi n ni n g t he st u d y , si g n t he Cli nical St u d y A gree me nt a n d c o m pl y wit h t he 
I n v esti gat or res p o nsi bilities as descri b e d i n s uc h A gree me nt.   
•  Pri or t o be gi n ni n g t he st u d y, si g n t he Pr ot oc ol Si g nat ure pa g e d oc u me nti n g his/ her 
a gree m e nt t o c o n d uct t he st u d y i n acc or da n ce wit h t he pr ot oc ol.  
•  Pr o vi de his/ her q ualificati o ns a n d e x perie n ce t o ass u me res p o nsi bilit y f or t he pr o per 
c o n d uct of t he st u d y a n d t hat of ke y me m bers of t he site tea m t hr o u g h u p-t o-date 
c urric ul u m vitae or ot h er rele va nt d oc u m e ntati o n a n d discl ose p ote ntial c o nflicts of 
i nterest, i ncl u di n g fi na ncial, t hat ma y i nterfere wit h t he c o n d uct of t he cli nical st u d y or 
i nter pretati o n of res ults. 
•  Ma ke n o c ha n ges i n or de viate fr o m t his pr ot oc ol, e xce pt t o pr otect t he life a n d p h ysical 
well -bei n g of a s u bject i n a n e mer g e nc y; d oc u me nt a n d e x plai n a n y de vi ati o n fr o m t he 
a p pr o ve d pr ot o c ol t hat occ urre d d uri n g t he c o urse of t he cli nical i n vesti gati o n.  
•  Create a n d m ai ntai n s o urce d oc u me nts t hr o u g h o ut t he cli nical st u d y a n d e ns ure t heir 
a vaila bilit y wit h direct access d uri n g m o nit ori n g visits or a u dits; e ns ure t hat all cli nical -
i n vesti gati o n-relate d rec or ds are retai ne d p er re q uire me nts. 
•  E ns ure t he acc urac y, c o m plete ness, le gi bilit y, a n d ti meli ness of t he data re p orte d t o t he 
s p o ns or i n t he C R Fs a n d i n all re q uire d re p orts. 
•  Rec or d, re p ort, a n d ass ess (seri o us ness a n d relati o ns hi p t o t he de vice/ pr oce d ure) e v er y 
a d verse e ve nt as a p plica ble per t he pr ot o c ol  a n d o bser ve d de vi ce deficie nc y.  
•  Re p ort t o s p o ns or, per t h e pr ot oc ol re q uir e me nts, all re p orta ble e ve nts. 
•  Re p ort t o t he I R B/ E C / R E B a n d re g ulat or y a ut h orities a n y S A Es a n d de vice deficie ncies 
t hat c o ul d ha ve le d t o a S A D E a n d p ote ntial/ U S A D E or U A D E , if re q uir e d b y a p plica ble 
la ws or re g ulati o ns or t his pr ot oc ol or b y t he I R B/ E C/ R E B, a n d s u p pl y B S C wit h a n y 
a d diti o nal re q ueste d i nf or mati o n relate d t o t he safet y re p orti n g of a p artic ul ar e ve nt.  
•  Mai ntai n t he de vice acc o u nta bilit y rec or ds a n d c o ntr ol of t he de vice, e ns uri n g t hat t he 
i n vesti gati o nal de vice is use d o nl y b y a ut h orize d/ desi g nate d users a n d i n acc or da n ce wit h 
t his pr ot oc ol a n d i nstr ucti o ns/ directi o ns f or use. 
•  All o w t he s p o ns or t o perf or m m o nit ori n g a n d a u diti n g acti vities a n d  be accessi ble t o t he 
cli nical researc h m o nit or or a u dit or a n d res p o n d t o q uesti o ns d uri n g m o nit ori n g visits  or 
a u dit(s). 

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•  All o w a n d s u p p ort re g ulat or y a ut h orities a n d t he I R B/ E C / R E B w he n perf or mi n g a u diti n g 
acti vities. 
•  E ns ure t hat i nf or me d c o nse nt is o btai ne d i n acc or da nce wit h a p plica ble la ws, t his 
pr ot oc ol a n d l ocal I R B/ E C / R E B re q uire me nts. 
•  Pr o vi de a de q uate m e dical care t o a s u bj ect d uri n g a n d after a s u bject’s parti ci pati o n i n a 
cli nical st u d y i n t he case of a d verse e ve nts, as des cri be d i n t he I nf or me d C o nse nt F or m 
(I C F). 
•  I nf or m t he s u bject of t h e nat ure a n d p ossi ble ca use of a n y a d verse e v e nts e x perie nce d. 
•  As a p plica ble, pr o vi d e t he s u bject wit h necessar y i nstr ucti o ns o n pr o per use, ha n dli n g, 
st ora ge, a n d ret ur n of t he i n vesti gati o nal de vice w he n it is use d/ o perate d b y t he s u bject.  
•  I nf or m t he s u bject of a n y ne w si g nifica nt fi n di n gs occ urri n g d uri n g t he cli nical 
i n vesti gati o n, i ncl u di n g t he nee d f or a d diti o nal me dical care t hat ma y be re q uire d. 
•  Pr o vi de t he s u bject wit h well -defi ne d pr oce d ures f or p ossi ble e mer g e nc y sit uati o ns 
relate d t o t he cli nic al st u d y, a n d ma ke t he necess ar y arra n ge me nts f or e mer ge nc y 
treat me nt, i ncl u di n g dec o di n g pr oce d ures f or bli n d e d/ mas ke d cli nical i n vesti gati o ns, as 
nee d e d.  
•  E ns ure t hat cli nical me di cal rec or ds are cl earl y m ar ke d t o i n dicate t h at t he s u bject is 
e nr olle d i n t his cli nical st u d y.  
•  E ns ure t hat, if a p pr o priat e, s u bjects e nr olle d i n t he cli nical i n vesti gati o n are pr o vi de d 
wit h s o me mea ns of s h o wi n g t heir partici pati o n i n t he cli nical i n vesti gati o n, t o get her wit h 
i de ntificati o n a n d c o m plia nce i nf or mati o n f or c o n c o mita nt treat me nt meas ures (c o ntact 
a d dress a n d tel e p h o ne n u m bers s hall be pr o vi de d).  
•  I nf or m, wit h t he s u bject’s a p pr o val or w h e n re q uire d b y nati o nal r e g ulati o ns, t he 
s u bject’s pers o n al p h ysicia n a b o ut t he s u bject’s partici pati o n i n t he cli nical i n vesti gati o n.  
•  Ma ke all reas o na ble eff orts t o ascertai n t he reas o n(s) f or a s u bject’s pre mat ure 
wit h dra wal fr o m cli nical i n vesti gati o n w hile f ull y res pecti n g t he s u bject’s ri g hts.  
•  E ns ure t hat a n a d e q uate i n vesti gati o n site tea m a n d facilities e xist a n d are mai ntai ne d a n d 
d oc u me nte d d uri n g t he cli nical i n vesti gati o n.  
 
All i n vesti gat ors will p r o vi de t heir q ualificati o ns a n d e x perie n ce t o ass u me res p o nsi bilit y f or 
t heir dele gate d t as ks t hr o u g h u p-t o-date c urric ul u m vitae or ot her rele va nt d oc u me ntati o n a n d 
discl ose p ote ntial c o nflicts of i nterest, i ncl u di n g fi na ncial, t hat ma y i nterfere wit h t he c o n d uct 
of t he cli nical st u d y or i nter pretati o n of res ults.  
 
1 8. 2. 1.  Dele g ati o n of Res p o nsi bilit y  
W he n s pecific tas ks are d ele gate d b y a n i n vesti gat or, i ncl u di n g b ut n ot li mite d t o c o n d ucti n g 
t he i nf or me d c o nse nt pr ocess, t he Pri nci pal I n v esti gat or is res p o nsi ble f or pr o vi di n g 

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a p pr o priate trai ni n g , are c o m pete nt t o perf or m t he tas ks t he y ha ve bee n del e gate d a n d 
a de q uate s u p er visi o n of t h ose t o w h o m tas ks are d ele gate d. W here t here is a s u b i n vesti gat or 
at a site, t he s u b i n vesti gat or s h o ul d n ot be dele gate d t he pri mar y s u per vis or y res p o nsi bilit y 
f or t he site. T he i n vesti gat or is acc o u nta ble f or re g ulat or y vi olati o ns res ulti n g fr o m fail ure t o 
a de q uatel y s u per vise t he c o n d uct of t he cli nical st u d y.  
1 8. 3.  I nstit uti o n al Revie w B o ar d/ Et hics C o m mittee 
T he i n vesti gati o nal site will  o btai n t he writte n a n d date d a p pr o val/fa v ora ble o pi ni o n of t he 
I R B/E C/ R E B  f or t he cli nical i n vesti gati o n bef ore recr uiti n g s u bjects a n d i m ple me nti n g all 
s u bse q ue nt a me n d me nts, if re q uire d. 
A c o p y of t he writte n I R B/ E C / R E B a n d/ or c o m pete nt a ut h orit y ( C A) a p pr o val of t he 
pr ot oc ol ( or per missi o n t o c o n d uct t he st u d y) a n d I C F, m ust be recei ve d b y t he s p o ns or 
bef ore recr uit me nt of s u bjects i nt o t he st u d y a n d s hi p me nt of i n vesti gati o nal 
pr o d uct/e q ui p me nt . Pri or a p pr o val m ust als o be o btai ne d f or ot her m aterials relate d t o s u bject 
recr uit me nt or w hi c h will be pr o vi de d t o t he s u bject . 
A n y a me n d me nt t o t he pr ot oc ol will re q uire re vi e w a n d a p pr o val b y t he I R B / E C/ R E B bef ore 
t he c ha n ges are i m ple me nte d t o t he st u d y.  All c ha n ges t o t he I C F will be I R B/ E C/ R E B 
a p pr o ve d ; a d eter mi nati o n will be ma de re g ar di n g w het her a n e w I C F nee ds t o be o btai ne d 
fr o m partici pa nts w h o pr o vi de d c o nse nt , usi n g a pre vi o usl y a p pr o ve d I C F. A n n ual 
I R B/E C / R E B a p pr o val a n d re ne w als will be o btai ne d t hr o u g h o ut t he d urati o n of t he st u d y as 
re q uire d b y a p plica ble l o cal/c o u ntr y la ws or re g ul ati o ns or I R B/ E C / R E B re q uire me nts. 
C o pies of t he st u d y re p orts a n d t he I R B/ E C/ R E B c o nti n ua nce of a p pr o val m ust be pr o vi de d 
t o t he s p o ns or.  
1 8. 4.  S p o ns or Res p o nsi bilities  
All i nf or mati o n a n d data se nt t o B S C c o ncer ni n g s u bjects or t heir partici pati o n i n t his st u d y 
will be c o nsi dere d c o nfi d e ntial b y B S C  a n d will be ke pt c o nfi de ntial i n acc or da nce wit h all 
a p plica ble la ws a n d re g ul ati o ns . O nl y a ut h orize d B S C pers o n nel a n d/or a B S C re prese ntati ve 
i ncl u di n g, b ut n ot li mite d t o C o ntract R esearc h O r ga nizati o n ( C R O), will ha ve access t o t his 
i nf or mati o n. A ut h orize d re g ulat or y pers o n nel ha ve t he ri g ht t o i ns pect a n d c o p y all rec or ds 
perti ne nt t o t his st u d y. St u d y data c ollecte d d uri n g t his st u d y ma y be use d b y B S C f or t he 
p ur p oses of t his st u d y, p u blicati o n, a n d t o s u p p ort f ut ure res earc h a n d/ or ot her b usi ness 
p ur p oses , s uc h as o v erseei n g a n d i m pr o vi n g t he perf or ma n ce of its de vice, ne w me dical 
researc h, a n d pr o p osals f or de vel o pi n g ne w me di cal pr o d ucts a n d pr o ce d ures . All data use d 
i n t he a nal ysis a n d re p orti n g of t his st u d y or s hare d wit h a t hir d -part y researc her will be 
wit h o ut i de ntifia ble refere nce t o s pecific s u bject s. 
I nf or mati o n recei ve d d uri n g t he st u d y will n ot be use d t o mar ket t o s u bjects; s u bject na mes 
will n ot be place d o n a n y maili n g lists or s ol d t o a n y o ne f or mar keti n g p ur p oses.   

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1 8. 4. 1.  R ole of B ost o n Scie ntific Re pres e nt ati ves  
B ost o n Scie ntific pers o n nel ca n pr o vi de t ec h nical s u p p ort t o t he i n vesti gat or a n d ot her h ealt h 
care p ers o n nel (c ollecti v el y H C P) as nee d e d d uri n g i m pla nt, testi n g re q uire d b y t he pr ot oc ol, 
a n d f oll o w-u ps. S u p p ort ma y i ncl u de H C P trai ni n g, a d dressi n g H C P q u esti o ns, or pr o vi di n g 
clarificati o ns t o H C Ps c o ncer ni n g t he o perati o n of B S C de vices.  
 
At t he re q uest of t he i n v esti gat or a n d w hile u n der i n vesti gat or s u per visi o n, B S C  pers o n nel 
ma y assist wit h t he c o n d uct of testi n g s pecifie d i n t he pr ot oc ol  a n d may perf or m certai n 
acti vities t o e ns ure st u d y q ualit y .  
T y pical tas ks ma y i ncl u d e t he f oll o wi n g : 
•  Pr o vi di n g tec h nical e x pertise/s u p p ort d uri n g i m pla nt pr oce d ures a n d/ or L A A i ma gi n g  
e val uati o ns i n c o nj u ncti o n wit h t he pri nci pal i n vesti gat or or t heir dele gate d site staff  
•  O bser vi n g testi n g or me dical pr oce d ures t o pr o vi d e i nf or mati o n rele va nt t o pr ot oc ol 
c o m plia nce  
•  Re vie wi n g c ollecte d d ata a n d st u d y d oc u me ntati o n f or c o m plete ness a n d acc urac y  
B ost o n Scie ntific pers o n nel will n ot d o t he f oll o wi n g:  
•  Practice me dici n e  
•  Pr o vi de me dical dia g n osis or treat me nt t o s u bjects  
•  Disc uss a s u bject’s c o n diti o n or treat me nt wit h a s u bject  
•  I n d e pe n de ntl y c ollect critical st u d y data ( defi ne d as pri mar y or sec o n dar y e n d p oi nt data) 
•  E nter data i n ele ctr o nic d ata ca pt ur e s yste ms or o n pa per case re p ort f or ms  
1 8. 5.  I ns ur a nce  
W here re q uir e d b y l ocal/ c o u ntr y re g ulati o n, pr o of,  a n d t y pe of i ns ura n ce c o vera ge, b y B S C 
f or s u bjects i n t he st u d y will be o btai ne d. 
1 9.  M o nit ori n g  
M o nit ori n g will be perf or me d d uri n g t he st u d y t o assess c o nti n ue d c o m plia nce wit h t he 
pr ot oc ol a n d a p plica bl e re g ulati o ns. I n a d diti o n, t he cli nical res earc h m o nit or verifies t hat 
st u d y rec or ds are a de q uat el y mai ntai ne d, t hat data are re p orte d i n a s atisfact or y ma n ner wit h 
res pect t o ti meli ness, a de q uac y, a n d acc urac y, a n d t hat t he Pri nci pal I n vesti gat or c o nti n ues t o 
ha ve s uffici e nt staff a n d facilities t o c o n d uct t he st u d y safel y a n d effecti vel y. T he Pri nci pal 
I n v esti gat or/i nstit uti o n g uara nte es direct access t o ori gi nal s o urce d oc u m e nts b y B S C 
pers o n nel, t heir desi g n ees, a n d a p pr o pri ate re g ul at or y a ut h orities.  
 
T he s p o ns or will p ut a pla n i n place t o d oc u m e nt t he s pecific m o nit ori n g re q uire me nts.  
 

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T he st u d y ma y als o be s u bject t o a q ualit y ass ura n ce a u dit b y B S C or its desi g nees, as well as 
i ns pecti o n b y a p pr o priate re g ulat or y a ut h orities. It is i m p orta nt t hat t he Pri nci pal  I n vesti gat or 
a n d rele v a nt st u d y pers o n nel are a vaila ble d uri n g o n -site m o nit ori n g visits or a u dits a n d t hat 
s ufficie nt ti me is de v ote d t o t he pr ocess. 
2 0.  P ote nti al Ris ks a n d Be nefits  
2 0. 1.  A ntici p ate d A dverse E ve nts   
P ote ntial pr oce d ural ris ks ass ociate d wit h t he W A T C H M A N F L X i m pla nt pr oce d ure a n d a 
car diac a blati o n are si milar t o t h ose e nc o u nt ere d i n ot her i nter ve nti o nal car diac pr oce d ures 
re q uiri n g tra ns-s e ptal p u nct ure a n d i ntracar diac cat heter ma ni p ulati o n a n d car diac 
cat heteri zati o n pr oce d ures.  T hese are i ncl u de d i n t he ta ble bel o w. 
T a ble 2 0. 1 -1 : A ntici p ate d A d verse E ve nts 
• Air e m b olis m  
• Air wa y tra u ma  
• Aller gic reacti o n t o t he c o ntrast me dia, 
a nest hetic, W A T C H M A N I m pla nt material, or 
me dicati o n  
• Altere d me ntal stat us  
• A ne mia re q uiri n g tra nsf usi o n  
• A nest hesia ris ks  
• A n gi na  
• A n o xic e nce p hal o pat h y  
• Arr h yt h mias  
• Atrial se ptal defect  
• Br uisi n g, he mat o ma or ser o ma  near t he cat heter 
i nserti o n site 
• Car diac perf orati o n  
• C hest pai n/ disc o mf ort  
• C o nf usi o n p ost pr oce d ure  
• C o n gesti ve heart fail ure  
• C o ntrast relate d ne p hr o pat h y  
• Cra nial blee d  
• Deat h  
• Decrease d he m o gl o bi n  
• Dee p vei n t hr o m b osis  
• De vice e m b olis m  
• De vice fract ure  
• De vice t hr o m b osis  
• E de ma  
• E m b olis m  
• E xcessi ve blee di n g  
• Fe ver  
• H y p ote nsi o n  
• H y p o xia  
• I m pr o per w o u n d heali n g  
• I na bilit y t o re p ositi o n, reca pt ure, or retrie ve t he 
de vice  
• I nfecti o n / p ne u m o nia  
• I nteratrial se pt u m t hr o m b us 
• I ntratrac heal blee di n g 
• Maj or blee di n g re q uiri n g tra nsf usi o n  
• Mis place me nt of t he de vice / i m pr o per seal of t he 
a p pe n da ge / m o ve me nt of de vice fr o m a p pe n da ge 
wall  
• M y ocar dial er osi o n  
• Na usea  
• Oral blee di n g  
• Pericar dial eff usi o n / ta m p o na de  
• Ple ural eff usi o n  
• Pr ol o n ge d blee di n g fr o m a lacerati o n  
• Pse u d oa ne ur ys m  
• P ul m o nar y e de ma  
• Re nal fail ure  
• Res pirat or y i ns ufficie nc y / fail ure  
• Str o ke –  Isc he mic  
• Str o ke –  He m orr ha gic  
• S ur gical re m o val of t he de vice  
• S yste mic e m b olis m  
• T E E c o m plicati o ns ( e. g., t hr oat pai n, blee di n g, 
es o p ha geal tra u ma)  
• T hr o m b oc yt o pe nia  
• T hr o m b osis  

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• F ist ula 
• Gr oi n pai n  
• Gr oi n p u nct ure blee d  
• He mat uria  
• He m o pt ysis  
• Tra nsie nt isc he mic attac k ( TI A)  
• Val v ular or vasc ular da ma ge  
• Vas o va gal reacti o ns  
 
2 0. 2.  A ntici p ate d A dverse Device Effects    
Fr o m t he A ntici pate d A d verse E ve nts liste d a b o v e, t he f oll o wi n g a ntici pate d a d verse d e vice 
effects ( A D E) ha ve b ee n i de ntifie d f or  t he W A T C H M A N F L X De vice a n d are as f oll o ws: 
•  A d diti o nal s ur ger y if t he de vice is n ot place d i n t h e c orrect p ositi o n  
•  Aller gic reacti o n t o t he i m pla nt materials  
•  De vice mis place me nt  
•  De vice e m b olizati o n/ mi grati o n  
•  De vice fract ure or e xtr usi o n  
•  E xcessi ve blee di n g  
•  H y pertr o p hic s carri n g or t hr o m b ose d vei ns  
•  De vice t hr o m b osis  
•  I n a bilit y t o m o ve or retri e ve de vice 
•  I n a bilit y t o i m pla nt t he de vice  
2 0. 3.  Ris ks Ass oci ate d wit h t he St u dy Device  
A n o ver vie w of a ntici pat e d a d vers e ( de vi ce) effects a n d ris ks ass ociate d wit h t he 
W A T C H M A N F L X de vi ce is i ncl u de d i n t he b ot h t he c o m mercial a n d t he st u d y I nstr ucti o ns 
f or Use (IF U).  
2 0. 4.  Ris ks ass oci ate d wit h P artici p ati o n i n t he Cli nic al St u dy  
S u bjects w h o recei ve t he W A T C H M A N F L X D e vice ma y st o p a ntic oa g ulati o n t hera p y as 
earl y as t he 3 -m o nt hs  f oll o w-u p visit if t he y meet a ntic oa g ulati o n  cess ati o n g ui deli nes; 
t heref ore, at t hat ti me, s u bjects ma y be at a n i n crease d ris k of str o ke.   A ntic oa g ulati o n is  t he 
m ost fre q ue ntl y utilize d m o dalit y  f or re d uci n g t he ris k of str o ke i n atrial fi brillati o n.  T he 
W A T C H M A N F L X D e vice is desi g ne d t o be use d i nstea d of l o n g-ter m a nti c oa g ulati o n.  T he 
a bse nce of a n a ntic oa g ul a nt ma y re prese nt  a ris k, es peciall y if t he d e vice is n ot effecti ve i n 
pre ve nti n g str o ke.  
 
F or s u bjects i n t he c o n c o mita nt gr o u p  (i.e., w h o will u n der g o a blati o n +/ - W A T C H M A N 
i m pla ntati o n), ris ks ass ociate d wit h t he a blati o n pr oce d ure s h o ul d b e disc usse d wit h t he 
p h ysicia n.  A d diti o nall y, it is c urre ntl y n ot k n o w n w het her s u bjects i n t he c o nc o mita nt gr o u p 
ma y be at i ncrease d ris k f or de vic e e m b olizati o n  or ot her a d v erse e ve nts  d ue t o t he c o m bi ne d 

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a blati o n a n d W A T C H M A N F L X i m pla nt.  It is e x pecte d t hat t he ris ks ass ociate d wit h t he 
c o nc o mita nt pr oce d ure are si milar t o t he ris k of w he n eac h pr oce d ure is perf or me d 
se parat el y.   
2 0. 5.  Me dic ati o n Ris ks  
Ris ks ass ociate d wit h O A C or a nti platelet usa g e  s h o ul d be refere nce d i n eac h me dicati o n’s I F U 
a n d ma y i ncl u de t he f oll o wi n g:  
•  I n crease d br uisi n g 
•  I n crease d ble e di n g te n de ncies 
•  Gastr oi ntesti nal ( GI) si de effects i ncl u di n g st o mac h pai n, heart b ur n, n a usea, v o miti n g 
a n d gr oss GI ble e di n g  
•  Ele vate d he p atic e nz y m es, bl o o d urea nitr o ge n a n d ser u m creati ni ne, h y per kale mia, 
pr otei n uria,  a n d pr ol o n g e d blee di n g ti me  
•  T hr o m b otic t hr o m b oc yt o pe nic p ur p ura ( T T P)  
•  T hr o m b oc yt o pe nia  
2 0. 6.  Ris k Mi ni miz ati o n Acti o ns  
A d diti o nal ris ks ma y e xist. Ris ks ca n be mi ni mize d t hr o u g h c o m plia nce wit h t his pr ot oc ol, 
perf or mi n g pr o ce d ures i n t he a p pr o priat e h os pital e n vir o n me nt, a d here nce t o s u bject 
selecti o n criteri a, f oll o wi n g of t he IF U f or me di cati o n a d mi nistrati o n,  cl ose m o nit ori n g of t he 
s u bject's p h ysi ol o gic stat us d uri n g researc h pr oce d ures a n d/ or f oll o w -u ps a n d b y pr o m ptl y 
s u p pl yi n g B S C  wit h all perti ne nt i nf or mati o n re q uire d b y t his pr ot oc ol.  
2 0. 7.  A ntici p ate d Be nefits  
W A T C H M A N F L X is d esi g ne d  t o e n ha nce t he us er e x perie nce a n d ac ute s afet y pr ofile f or 
t he W A T C H M A N L A A Cl os ure Tec h n ol o g y c o m pare d t o t he W A T C H M A N L A A C De vice 
(als o calle d W A T C H M A N Ge n 2. 5).  T h e p ote ntial be nefit of i m pla nti n g t he W A T C H M A N 
F L X D e vice is its e x pect e d a bilit y t o pre ve nt t hr o m b oe m b olic e ve nts ori gi nati n g i n t he L A A.  
T he W A T C H M A N F L X D e vice ma y pr otect a gai nst isc he mic str o ke a n d s yste mic 
t hr o m b oe m b olis m.  I n s u bjects i m pla nte d wit h t he de vice, t he eli mi nati o n of l o n g-ter m 
a ntic oa g ulati o n  t hera p y ma y re d uce blee di n g c o m plicati o ns ass ociate d wit h l o n g -ter m 
a ntic oa g ulati o n , s uc h as he m orr ha gic str o ke or gastr oi ntesti nal maj or blee di n g e ve nts .  
2 0. 8.  Ris k t o Be nefit R ati o n ale  
Ris k ma na ge me nt acti vities, i ncl u di n g Hazar d A nal yse s ( H A) a n d Fail ure M o de Effects 
A nal yses ( F M E A), ha v e bee n perf or me d o n t he W A T C H M A N F L X De vice t o i de ntif y a n d 
a nal yze k n o w n a n d f ores eea ble h azar ds a n d reas o na bl y f oreseea ble s e q ue n ces or 
c o m bi nati o ns of e ve nts t hat c o ul d res ult fr o m usi n g t his pr o d uct a n d t he ris ks ass ociate d wit h 
eac h h azar d.   Miti gati o ns ha ve bee n i m ple me nte d i n t he desi g n, pr ocesses, a n d/ or la beli n g 
a n d directi o ns  f or us e of t he pr o d uct t o re d u ce t he resi d ual ris k of eac h hazar d as necessar y 

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a n d practica ble.  T he H A  has bee n re vie we d a n d a p pr o ve d a n d t he re mai ni n g ris ks are 
acce pta ble w h e n wei g he d a gai nst t he i nte n de d be nefits t o t he s u bject. 
 
I n a d diti o n, in vesti gati o nal tea ms selecte d t o c o n d uct t he st u d y will be e x perie nce d a n d 
s kille d i n i nter ve nti o nal car di ol o g y a n d/ or electr o p h ysi ol o g y wit h tra nsse ptal a n d left heart 
e x perie n ce, will ha ve c o m plete d t he W A T C H M A N F L X P h ysicia n Trai ni n g pr o gra m a n d 
will ha ve access t o m o der n hi g h tec h n ol o g y me dical facilities t o c o n d uct t h ose pr oce d ures . 
2 1.  S afet y Re p orti n g  
2 1. 1.  Re p ort a ble Eve nts  by i nvesti g ati o n al site t o B ost o n Scie ntific  
It is t he res p o nsi bilit y of t he i n vesti gat or t o assess a n d re p ort t o B S C a n y e v e nt w hic h occ urs 
fr o m ti me of e nr oll me nt t hr o u g h 3-year f oll o w -u p i ncl u di n g  a n y of f oll o wi n g cate g ories:  
•  U na ntici pate d A d v erse D e vice Effects/ U na ntici pate d Seri o us A d verse De vi ce Effects  
•  Seri o us A d vers e E ve nts re gar dl ess of ca use - Pla n ne d h os pitalizati o n f or a pre -e xisti n g 
c o n diti o n, or a pr oce d ure re q uire d b y t he cli nical i n vesti gati o nal pla n, wit h o ut seri o us 
deteri orati o n i n he alt h, is n ot c o nsi dere d a s eri o us a d verse e ve nt.  
I n a d diti o n, t he f oll o wi n g e ve nts m ust als o be re p orte d: 
•  W A T C H M A N F L X De vice a n d/ or W A T C H M A N F L X i n de x pr oce d ure relate d a d v erse 
e ve nts  
•  A d verse e ve nts rel ate d t o pr ot oc ol re q uire d t esti n g ( i.e., T E E  or ot her L A A i ma gi n g ) 
•  A d verse e ve nts w here s yste mic e m b olis m is s us pecte d a n d/ or c o nfir me d, re gar dless 
of relati o ns hi p t o t he W A T C H M A N F L X De vice.  
•  A d verse e ve nts rel ate d t o W A T C H M A N F L X De vice ( de vice t hr o m b us, 
e m b olizati o n, er osi o n, et c.).  
•  A d verse e ve nts rel ate d t o t he  a blati o n pr oce d ure (if t he pr oce d ure o cc urre d after 
c o nse nt)  
•  A d verse e ve nts rel ate d t o pr ot oc ol re q uire d  O A C or a nti platelet t hera p y  
•  All blee di n g e ve nts re g ar dless of relati o ns hi p t o t he W A T C H M A N F L X De vice.  
•  All str o kes (re g ar dless of ca use) a n d tra nsie nt isc h e mic ( TI A) re g ar dless of 
relati o ns hi p t o t he W A T C H M A N F L X De vice. 
•  Ne w fi n di n gs/ u p dates i n relati o n t o alrea d y re p orte d e ve nts  
W he n p ossi ble, t he me di cal dia g n osis s h o ul d be re p orte d as t he E ve nt Ter m i nstea d of 
i n di vi d ual s y m pt o ms. 

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If it is u nclear w h et her or n ot a n e ve nt fits o ne of t he a b o ve cate g ori es, or if t he e ve nt ca n n ot 
be is olate d fr o m t he de vi ce or i n de x pr oce d ure, it s h o ul d be s u b mitte d as a n a d verse e ve nt 
a n d/ or de vice d eficie n c y.  
A n y re p orta bl e e ve nt  e x p erie nce d b y t he st u d y s u bject after i nf or me d c o ns e nt a n d o nce 
c o nsi dere d e nr olle d i n t he st u d y (as defi n e d i n st u d y s u bject classificati o n secti o n)  m ust be 
rec or de d i n t he e C R F.   
U n derl yi n g diseases are n ot re p orte d as A Es u nless t here is a n i ncrease i n se verit y o r 
fre q ue n c y d uri n g t he c o urse of t he i n vesti gati o n. Deat h s h o ul d n ot be rec or de d as a n A E b ut  
s h o ul d o nl y be reflect e d as a n o utc o me of o n e ( 1) s pecific S A E (s ee Ta bl e 2 1. 2 -1  f or A E 
defi niti o ns).  
Atrial fi brillati o n rec urre nce is n ot c o nsi dere d a n A E u nless t here is a w ors e ni n g of t he 
c o n diti o n as deter mi ne d b y t he i n vesti gat or.   If a n a d diti o nal a blati o n pr oce d ure is re q uir e d 
b y a n y s u bject, t he pr oce d ure s h o ul d be re p orte d i n t he A E e C R F w he ne ver it meets t he 
criteria f or a seri o us a d verse e ve nt or re prese nts a w orse ni n g c o n diti o n.  T he a blati o n s h o ul d 
be re p ort e d as a c orrecti v e  acti o n f or t h e s u bject c o n diti o n.  
Refer t o Secti o n 2 0  f or t h e k n o w n ris ks ass ociat e d wit h t he st u d y de vice(s). 
2 1. 2.  Defi niti o ns a n d Cl assific ati o n  
A d verse e ve nt defi niti o ns are pr o vi de d i n  Ta ble 2 1. 2 -1 . A d mi nistrati ve  e dits were ma de o n 
t he safet y defi niti o n s fr o m a p plica ble re g ul ati o ns a n d g ui da nce  i n cl u di n g ( b ut n ot li mite d t o) 
2 1 C F R Part 8 1 5,  I S O 1 4 1 5 5 a n d E U M D R 2 0 1 7/ 7 4 5/ M D C G 2 0 2 0 -1 0 /1 G ui da nce o n S afet y 
R e p orti n g i n C li nical In v esti gati o ns  f or clarifi cati o n p ur p oses. 
 
T a ble 2 1. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
A d verse E ve nt ( A E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1  
 
 
 
 
A n y u nt o war d me dical occ urre nce, u ni nte n de d disease or i nj ur y, or a n y 
u nt o war d cli nical si g ns (i ncl u di n g a n a b n or mal la b orat or y fi n di n g) i n 
s u bjects, users or ot her pers o ns, i n t he c o nte xt of a cli nical i n vesti gati o n, 
w het her or n ot relate d t o t he i n vesti gati o nal me dical de vice  a n d w het her 
a ntici pate d or u na ntici pate d .  
N O T E 1 : T his i ncl u des e ve nts relate d t o t he i n vesti gati o nal me dical 
de vice or c o m parat or.  
N O T E 2 : T his defi niti o n i ncl u des e ve nts relate d t o t he pr oce d ures 
i n v ol ve d. 
N O T E 3 : F or users or ot her pers o ns, t his defi niti o n is restricte d t o e ve nts 
relate d t o t he i n vesti gati o nal me dical de vice.  
A d verse De vice Effect ( A D E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref:  M D C G 2 0 2 0 -1 0/ 1  
A d verse e ve nt relate d t o t he use of a n i n vesti gati o nal me dical de vice  
N O T E 1 : T his  i ncl u des a n y a d verse e ve nt res ulti n g fr o m i ns ufficie ncies 
or i na de q ua cies i n t he i nstr ucti o ns f or use, t he de pl o y me nt, t he 
i m pla ntati o n, t he i nstallati o n, t he o perati o n, or a n y malf u ncti o n of t he 
i n vesti gati o nal me dical de vice. 

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T a ble 2 1. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
N O T E 2 : T his defi niti o n i ncl u des a n y e ve nt res ulti n g fr o m use err or or 
fr o m i nte nti o nal mis use of t he i n vesti gati o nal me dical de vice.  
N O T E 3 : T his i ncl u des ‘c o m parat or’ if t he c o m parat or is a me dical 
de vice.  
Seri o us A d verse E ve nt ( S A E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1  
A d verse e ve nt t hat  le d t o a n y of f oll o wi n g: 
a) D eat h , 
b)  S eri o us deteri orati o n i n t he healt h of t he s u bject , users or ot her pers o ns 
as defi ne d b y  eit her : 
1)  a life -t hreate ni n g ill ness or i nj ur y, or 
2)  a per ma ne nt i m pair me nt of a b o d y str uct ure or a b o d y f u ncti o n, 
i ncl u di n g c hro n ic diseases, or  
3)  i n-patie nt h os pitalizati o n or pr ol o n g ati o n of e xisti n g  
h os pitalizati o n , or 
4)  me dical or s ur gical i nter ve nti o n t o pre ve nt life -t hreate ni n g ill ness 
or  i nj ur y or per ma ne nt i m pair me nt t o a b o d y str uct ure or a b o d y 
f u ncti o n 
c) Le d t o fetal distress, fetal deat h, or a c o n ge nital a b n or malit y or birt h 
defect  i ncl u di n g p h ysical or me ntal i m pair me nt. 
N O T E 1 : Pla n ne d h os pitalizati o n  f or a pre-e xisti n g c o n diti o n, or a 
pr oce d ure re q uire d b y t he cli nical i n vesti gati o nal pla n, wit h o ut a seri o us 
deteri orati o n i n healt h, is n ot c o nsi dere d a seri o us a d verse e ve nt.  
Seri o us A d verse De vice Effect 
( S A D E) 
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1  
A d verse de vice effect t hat has res ulte d i n a n y of t he c o nse q ue nces 
c h aracteristic of a seri o us a d verse e ve nt.  
 
U na ntici pate d A d verse De vice 
Effect ( U A D E)  
 
Ref: 2 1 C F R P art 8 1 2  
 
 
A n y seri o us a d verse effect o n healt h or safet y or a n y life -t hreate ni n g 
pr o ble m or deat h ca use d b y, or ass ociate d wit h, a de vice, if t hat effect, 
pr o ble m, or deat h was n ot pre vi o usl y i de ntifie d i n nat ure, se verit y, or 
de gree of i nci de nce i n t he i n vesti gati o nal pla n or a p plicati o n (i ncl u di n g a 
s u p ple me ntar y pla n or a p plicati o n), or a n y ot her u na ntici pate d seri o us 
pr o ble m ass ociate d wit h a de vice t hat relates t o t he ri g hts, safet y, or 
welfare of s u bjects.   
U na ntici pate d Seri o us A d verse 
De vice Effect ( U S A D E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1  
 
 
Seri o us a d verse de vice effect w hic h b y its nat ure, i nci de nce, se verit y, or 
o utc o me has n ot bee n i de ntifie d i n t he c urre nt ris k assess me nt. 
N O T E 1 : A ntici pate d seri o us a d verse de vice effect ( A S A D E) is a n effect 
w hic h b y its nat ure, i nci de nce, se verit y, or o utc o me has bee n i de ntifie d i n 
t he ris k assess me nt . 
Seri o us Healt h T hreat  
 
S i g nal fr o m a n y a d verse e ve nt or de vice deficie nc y t hat i n dicates a n 
im mi ne nt ris k of deat h or a seri o us  deteri orati o n i n t he healt h i n s u bjects, 
users,  or ot her pers o ns, a n d t hat re q uires pr o m pt re me dial acti o n  

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T a ble 2 1. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
Ref: I S O 1 4 1 5 5  
 
f or ot her s u bjects, users,  or ot her pers o ns . 
N O T E  1 : T his w o ul d i ncl u de e ve nts t hat are of si g nifica nt a n d u ne x pecte d 
nat ure s uc h t hat t he y bec o me  alar mi n g as a p ote ntial seri o us healt h hazar d 
or p ossi bilit y of m ulti ple deat hs occ urri n g at s h ort i nter vals.  
De vice Deficie n c y  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1  
A n  ina de q uac y of a  me dical de vice relate d t o its i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, usa bilit y, safet y, or perf or ma nce.   
N O T E 1 : De vice deficie ncies i ncl u de malf u ncti o ns, use err ors, a n d 
i na d e q uac y i n t he i nf or mati o n s u p plie d b y t he ma n ufact urer i ncl u di n g 
la belli n g. 
N O T E 2 : T his defi niti o n i ncl u des de vice deficie ncies relate d t o t he 
i n vesti gati o nal me dical de vice or t he c o m parat or. 
T he f oll o wi n g defi niti o ns will be use d f or defi ni n g h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n f or S A E 
classificati o n p ur p oses:  
H os pitalizati o ns  
H os pitalizati o n d oes n ot i ncl u de:  
•  
e mer ge nc y r o o m visit t hat d oes n ot res ult i n i n -patie nt a d missi o n  
N ote: alt h o u g h a n e mer ge nc y r o o m visit d oes n ot itself meet t he 
defi niti o n f or h os pitalizati o n, it ma y meet ot her seri o us criteria 
(e. g.,  me dical or s ur gical i nter ve nti o n t o pre ve nt per ma ne nt 
i m pair me nt or da ma ge) 
•  
electi ve a n d pre -pla n ne d treat me nt/s ur ger y f or a pre -e xisti n g 
c o n diti o n t hat is d oc u me nte d i n t he s u bject’s rec or d at t he ti me of 
c o nse nt/e nr oll me nt  
•  
a d missi o n f or s ocial reas o ns a n d/ or res pite care i n t he a bse nce of 
a n y deteri orati o n i n t he s u bject’s ge neral c o n diti o n  (e. g.,  s u bject 
is h o meless, care gi ver relief) 
•  
pre -pla n ne d, pr ot oc ol -s pecifie d a d missi o n relate d t o t he cli nical 
st u d y (e. g., pr oce d ure re q uire d b y pr ot oc ol)  
Pr ol o n gati o n of  h os pitalizati o n  
I n-patie nt a d missi o n t o t he h os pital t hat is pr ol o n ge d be y o n d t he e x pecte d 
sta n dar d d urati o n f or t he c o n diti o n u n der treat me nt. 
N ote: ne w a d verse e ve nts occ urri n g d uri n g t he h os pitalizati o n are 
e v al uate d t o deter mi ne if t he y pr ol o n ge d h os pitalizati o n or meet a n ot her 
S A E criteria.  
 
 
2 1. 3.  Rel ati o ns hi p  t o St u dy Device(s) 
T he I n vesti gat or m ust assess t he relati o ns hi p of t h e re p ort a ble A E t o t he st u d y de vice  a n d/or 
i n de x pr oce d ure . See crit eria i n T a ble 2 1. 3 -1 :  

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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 1  of 1 0 2  
 
  
T a ble 2 1. 3 -1 : Criteri a f or Assessi n g Rel ati o ns hi p of St u d y De vice, C o m p ar at or,  
Pr oce d ure  t o A d vers e E ve nt 
Cl assific ati o n  
Descri pti o n  
N ot R el ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
Relati o ns hi p t o t he de vice , c o m parat or, or pr oce d ures ca n be e xcl u de d w he n:  
- t he e v e nt is n ot a k n o w n si de effect of t he pr o d uct cate g or y t he de vice bel o n gs t o 
or of si milar de vices a n d pr oce d ures; 
- t he e v e nt has n o te m p oral relati o ns hi p wit h t he use of t he i n vesti gati o nal de vice or 
t he pr oce d ures; 
- t he seri o us e ve nt d oes n ot f oll o w a k n o w n res p o nse patter n t o t he me dical de vice 
(if t he res p o nse patter n is pre vi o usl y k n o w n) a n d is bi ol o gicall y i m pla usi ble; 
- t he disc o nti n uati o n of me dical de vice a p plicati o n or t he re d ucti o n of t he le vel of 
acti vati o n/e x p os ure - w he n cli nicall y feasi ble –  a n d rei ntr o d ucti o n of its use ( or 
i ncrease of t he le vel of acti vati o n/e x p os ure), d o n ot i m pact o n t he seri o us e ve nt; 
- t he e v e nt i n v ol ves a b o d y-site or a n or ga n n ot e x pecte d t o be affecte d b y t he 
de vice or pr oce d ure;  
- t he seri o us e ve nt ca n be attri b ute d t o a n ot her ca use (e. g. a n u n derl yi n g 
or c o nc urre nt ill ness/ cli nical c o n diti o n, a n effect of a n ot her de vice, dr u g, treat me nt 
or ot her ris k fact ors);  
- t he e v e nt d oes n ot de pe n d o n a false res ult gi ve n b y t he i n vesti gati o nal de vice 
use d f or dia g n osis, w he n a p plica ble; har ms t o t he s u bject are n ot clearl y d ue t o use 
err or; 
- I n or der t o esta blis h t he n o n-relate d ness, n ot all t he criteria liste d a b o ve mi g ht be 
met at t he sa me ti me, de pe n di n g o n t he t y pe of de vice/ pr oce d ures a n d t he seri o us 
e v e nt. 
U nli k el y Rel ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he relati o ns hi p wit h t he use of t he de vice see ms n ot rele v a nt a n d/ or t he e ve nt ca n 
be reas o na bl y e x plai ne d b y a n ot her ca use, b ut a d diti o nal i nf or mati o n ma y be 
o btai ne d.  
P ossi bl y Rel ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he relati o ns hi p wit h t he use of t he st u d y de vice or c o m parat or, or t he relati o ns hi p 
wit h pr oce d ures is wea k b ut ca n n ot be r ule d o ut c o m pletel y. Alter nati ve ca uses are 
als o p ossi ble ( e. g.,  a n u n derl yi n g or c o nc urre nt ill ness/ cli nical c o n diti o n or/a n d a n 
effect of a n ot her de vice, dr u g,  or treat me nt). Cases w here  relate d ness ca n n ot be 
assesse d,  or n o i nf or mati o n has bee n o btai ne d s h o ul d als o be classifie d as p ossi ble.  
Pr o b a bl y Rel ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he relati o ns hi p wit h t he use of t he st u d y de vice , c o m parat or, or t he relati o ns hi p 
wit h pr oce d ures  see ms rele v a nt a n d/ or t he e ve nt ca n n ot be reas o na bl y e x plai ne d b y 
a n ot her ca use, b ut a d diti o nal i nf or mati o n ma y be o btai ne d.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 2  of 1 0 2  
 
  
T a ble 2 1. 3 -1 : Criteri a f or Assessi n g Rel ati o ns hi p of St u d y De vice, C o m p ar at or,  
Pr oce d ure  t o A d vers e E ve nt 
Cl assific ati o n  
Descri pti o n  
C a us al Rel ati o ns hi p  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he seri o us e v e nt is ass ociate d wit h t he st u d y de vice or c o m parat or or wit h 
pr oce d ures be y o n d reas o na ble d o u bt w he n: 
- t he e v e nt is a k n o w n si de effect of t he pr o d uct cate g or y t he de vice bel o n gs t o or 
of si milar de vices a n d pr oce d ures;  
- t he e v e nt has a te m p oral relati o ns hi p wit h i n vesti gati o nal de vice use/a p plicati o n 
or pr oce d ures;  
- t he e v e nt i n v ol ves a b o d y-site or or ga n t hat 
-t he i n vesti gati o nal de vice or pr oce d ures are a p plie d t o; -t he 
i n vesti gati o nal de vice or pr oce d ures ha ve a n effect o n; 
- t he seri o us e ve nt f oll o ws a k n o w n res p o nse patter n t o t he me dical de vice (if t he 
res p o nse patter n is pre vi o usl y k n o w n); 
- t he disc o nti n uati o n of me dical de vice a p plicati o n ( or re d ucti o n of t he le vel of 
acti vati o n/e x p os ure) a n d rei ntr o d ucti o n of its use ( or i ncrease of t he le vel of 
acti vati o n/e x p os ure), i m pact o n t he seri o us e ve nt ( w he n cli nicall y feasi ble);  
- ot her p ossi ble ca uses (e. g. a n u n derl yi n g or c o nc urre nt ill ness/ cli nical c o n diti o n 
or/a n d a n effect of a n ot her de vice, dr u g or treat me nt) ha ve bee n a de q uatel y r ule d 
o ut;  
- har m t o t he s u bject is d ue t o err or i n use;  
- t he e v e nt de pe n ds o n a false res ult gi ve n b y t he i n vesti gati o nal de vice use d f or 
dia g n osis, w he n a p plica ble;  
- I n or der t o esta blis h t he relate d ness, n ot all t he criteria liste d a b o ve mi g ht be met 
at t he sa me ti me, de pe n di n g o n t he t y pe of de vice/ pr oce d ures a n d t he seri o us e v e nt.  
 
2 1. 4.  I nvesti g at or Re p orti n g Re q uire me nts 
T he c o m m u nicati o n re q uire me nts f or re p orti n g t o B S C are as s h o w n i n Ta ble 2 1. 4 -1 . 
T a ble 2 1. 4 -1 : I n vesti g at or Re p orti n g Re q uire me nts 
E ve nt Cl assific ati o n  
C o m m u nic ati o n Met h o d  
C o m m u nic ati o n Ti m eli ne  
(2 1 C F R Part 8 1 2, M D C G 2 0 2 0 -1 0/ 1 ) 
Seri o us Healt h T hreat  
C o m plete a p plica ble 
e C R F/ pa p er f or m  wit h all 
a v aila ble ne w a n d u p date d  
i nf or mati o n. 
•  
Wit hi n 1 b usi ness da y  of first 
bec o mi n g a ware of t he e ve nt.  
•  
Ter mi nati n g at t he e n d of t he st u d y.  
 
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -i de ntifie d/ 
pse u d o n y mize d) f or re p orte d 
e v e nt. 
•  
U p o n re q uest of s p o ns or.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 3  of 1 0 2  
 
  
T a ble 2 1. 4 -1 : I n vesti g at or Re p orti n g Re q uire me nts 
E ve nt Cl assific ati o n  
C o m m u nic ati o n Met h o d  
C o m m u nic ati o n Ti m eli ne  
(2 1 C F R Part 8 1 2, M D C G 2 0 2 0 -1 0/ 1 ) 
U na ntici pate d A d verse De vice 
Effect / U na ntici pate d Seri o us 
A d verse De vice Effect  
 
C o m plete A E e C R F pa ge wit h 
all a v aila ble ne w a n d u p date d 
i nf or mati o n.  
 
•  
Wit hi n 1 b usi ness da y of first 
bec o mi n g a ware of t he e ve nt.  
•  
Ter mi nati n g at t he e n d of t he st u d y  
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -i de ntifie d/ 
pse u d o n y mize d) f or re p orte d 
e v e nt.  
•  
U p o n re q uest of s p o ns or.  
Seri o us A d verse E ve nt   
C o m plete A E e C R F pa ge wit h 
all a v aila ble ne w a n d u p date d 
i nf or mati o n.  
•  
I m me diatel y, b ut n o later t ha n 3 
cale n dar da ys of first bec o mi n g a ware 
o f t he e ve nt or as per l ocal/re gi o nal 
re g ulati o ns.  
•  
Re p orti n g re q uire d t hr o u g h t he e n d of 
t he st u d y 
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -i de ntifie d/ 
pse u d o n y mize d) f or re p orte d 
e v e nt. 
•  
U p o n re q uest of s p o ns or  
Seri o us A d verse De vice Effects  
 
C o m plete A E e C R F pa ge wit h 
all a v aila ble ne w a n d u p date d 
i nf or mati o n. 
•  
I m me diatel y b ut n o later t ha n 3 cale n dar 
da ys of first bec o mi n g a ware  of t he e v e nt 
or as per l ocal/re gi o nal re g ulati o ns.  
•  
Re p orti n g re q uire d t hr o u g h t he e n d of t he 
st u d y 
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -i de ntifie d/ 
pse u d o n y mize d) f or re p orte d 
e v e nt.  
•  
W he n d oc u me ntati o n is a vaila ble  
•  
U p o n re q uest of s p o ns or  
De vice Deficie n cies  (i ncl u di n g 
b ut n ot li mite d t o , m alf u ncti o ns,  
use err ors  a n d i na d e q uac y i n 
i nf or mati o n s u p plie d b y t he 
ma n ufact urer, i ncl u di n g 
la beli n g) 
N ote:  A n y De vice Deficie n c y 
t hat mi g ht h a ve le d t o a seri o us 
a d verse e v e nt if a p pr o priate  
acti o n ha d n ot b ee n ta ke n, 
i nter ve nti o n ha d n ot occ urre d , 
circ u msta nces ha d bee n less 
f ort u nate is c o nsi dere d a 
re p orta ble e ve nt. 
C o m plete De vice Deficie nc y 
e C R F wit h all a vaila ble ne w a n d 
u p date d i nf or mati o n .  
•  
I m me diatel y b ut n o later t ha n 3 
cale n dar da ys of first bec o mi n g 
a ware of t he e ve nt .  
•  
Re p orti n g re q uire d t hr o u g h t he e n d 
of t he st u d y  
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -i de ntifie d/ 
pse u d o n y mize d) f or re p orte d 
e v e nt. 
•  
U p o n re q uest of s p o ns or  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 4  of 1 0 2  
 
  
T a ble 2 1. 4 -1 : I n vesti g at or Re p orti n g Re q uire me nts 
E ve nt Cl assific ati o n  
C o m m u nic ati o n Met h o d  
C o m m u nic ati o n Ti m eli ne  
(2 1 C F R Part 8 1 2, M D C G 2 0 2 0 -1 0/ 1 ) 
Re p orta ble A d verse E ve nt  (see 
secti o n 2 1) i ncl u di n g A d verse 
De vice Effects  
C o m plete A E e C R F pa ge, w hic h 
c o ntai ns s uc h i nf or mati o n as 
date of A E, treat me nt of A E 
res ol uti o n, assess me nt of 
seri o us ness a n d relati o ns hi p t o 
t he de vice.  
•  
I n a ti mel y ma n ner (e. g., 
Rec o m me n d wit hi n 1 0 b usi ness 
da ys) after bec o mi n g a ware of t he 
i nf or mati o n 
•  
Re p orti n g re q uire d t hr o u g h t he e n d 
of t he st u d y   
 
Pr o vi de all rele v a nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) f or 
re p orte d e ve nt, as re q ueste d b y 
s p o ns or.  
•  
U p o n re q uest of s p o ns or  
2 1. 5.  B ost o n Scie ntific Device Deficie ncies  
De vice  d eficie n cies  f or st u d y de vices ( W A T C H M A N F L X Deli ver y S yste m, c o nsisti n g of a 
deli ver y cat h eter a n d pre -l oa de d cl os ur e de vice ) will be d oc u me nte d a n d re p orte d t o B S C  o n 
t he De vice Defici e nc y e C R F. If p ossi ble, t he de vice(s) s h o ul d be ret ur ne d t o B S C f or 
a nal ysis. I nstr ucti o ns f or ret ur ni n g t he de vice(s) will be pr o vi de d  o n a n i n di vi d ual basis.  
De vice d eficie n cies  s h o ul d als o be d oc u me nte d i n t he s u bject’s s o urce rec or ds. 
 
De vice d eficie n cies  are n ot a d verse e ve nts. H o we ver, a n a d v erse e ve nt t hat res ults fr o m a 
de vice deficie nc y  w o ul d be rec or de d as a n a d v erse e ve nt o n t he a p pr o priat e e C R F.  
2 1. 6.  Re p orti n g t o Re g ul at ory A ut h orities / I R Bs / E Cs / R E Bs/ I nvesti g at ors 
B S C is res p o nsi ble f or re p orti n g a d verse e ve nt i nf or mati o n t o all partici pati n g Pri nci pal 
In v esti gat ors , I R Bs/ E Cs/ R E Bs a n d re g ulat or y a ut h orities, as a p plica ble.  
  
T he Pri nci pal I n vesti gat or is res p o nsi ble f or i nf or mi n g t he I R B/ E C / R E B, a n d re g ulat or y 
a ut h orities of U A D E s/ U S A D Es a n d S A Es as re q uire d b y l ocal /re gi o n al re g ulati o ns. 
2 1. 7.  S u bject De at h Re p orti n g  
A s u bject deat h t hat occ urs d uri n g t he st u d y s h o ul d be re p ort e d t o B ost o n Scie ntific as s o o n 
as p ossi ble a n d, i n a n y e v e nt, wit hi n t hree cal e n dar  da ys of ce nt er n otificati o n. T he ce nter’s 
I R B/ E C/ R E B m ust be n otifie d of a n y deat hs i n acc or da nce wit h t hat ce nt er’s I R B / E C/ R E B 
p olicies a n d pr oce d ures.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 5  of 1 0 2  
 
  
2 2.  I nf or me d C o nse nt 
S u bject partici pati o n i n t his cli nical st u d y is v ol u ntar y.  I nf or m e d C o nse nt is re q uire d fr o m  
eac h s u bject or his/ her le gall y a ut h orize d re pres e ntati ve . T he I n vesti gat or is res p o nsi ble f or 
e ns uri n g t hat I nf or me d C o nse nt is o btai ne d pri or t o t he use of a n y i n vesti gati o nal de vices, 
st u d y-re q uire d pr oce d ures a n d/ or testi n g, or data c ollecti o n.  
 
T he o btai ni n g a n d d oc u me ntati o n of I nf or me d C o nse nt m ust be i n acc or da nce wit h t he 
pri nci ples of t he Declarati o n of Helsi n ki, I S O 1 4 1 5 5, a n y a p plica ble nati o nal re g ulati o ns, a n d 
l ocal Et hics C o m mittee a n d/ or Re g ulat or y a ut h orit y, as a p plica ble. T h e I C F m ust be acce pt e d  
b y B S C or it s dele gate (e. g., C R O), a n d a p pr o ve d b y t he site’s I R B/ E C/ R E B, or ce ntral I R B, 
if a p plica ble. 
 
B ost o n Scie ntific will pr o vi de a st u d y -s pecifi c te m plate of t he I C F t o i n vesti gat ors 
partici pati n g i n t his st u d y. T he I C F te m plate m a y be m o difie d t o meet t he re q uire me nts of t he 
i n vesti gati ve site’s I R B/ E C/ R E B.  A n y m o dificati o n re q uires acce pt a nce fr o m B S C pri or t o 
use of t he f or m.  T h e I C F m ust be i n a la n g ua ge u n dersta n da ble t o t he s u bject a n d if nee d e d, 
B S C will assist t he site i n o btai ni n g a writte n c o nse nt tra nslati o n. Tra nslat e d c o nse nt f or ms 
m ust als o ha ve I R B/ E C / R E B a p pr o val pri or t o t heir use.  P ri vac y la n g ua g e s hall be i ncl u de d 
i n t he b o d y of t he f or m or as a se p arat e f or m as a p plica ble.  
  
T he pr ocess of o btai ni n g I nf or me d C o nse nt s hall  at a mi ni m u m i ncl u de t he f oll o wi n g ste ps, 
as well as a n y ot her ste ps re q uire d b y a p plica ble la ws, r ules, re g ulati o ns, a n d g ui deli nes : 
•  be c o n d ucte d b y t h e Pri nci pal I n vesti gat or or d esi g nee a ut h orize d t o c o n d uct t he pr ocess,  
•  i ncl u de a descri pti o n of all as pects of t he cli nical st u d y t hat are rele va nt t o t he s u bject’s 
decisi o n t o partici pate t hr o u g h o ut t he cli nical st u d y,  
•  a v oi d a n y c oerci o n of or u n d ue i nfl ue nce of s u bjects t o partici pate,  
•  n ot wai ve or a p p ear t o wai ve s u bject’s le gal ri g hts,  
•  use nati ve la n g ua g e t hat is n o n -tec h nical a n d u n dersta n da ble t o t he s u bject or his/ her 
le gal re prese ntati ve, 
•  pr o vi de a m ple ti me f or t h e s u bject t o c o nsi der partici pati o n a n d as k q uesti o ns if 
necessar y,  
•  e ns ure i m p orta nt ne w i nf or mati o n is pr o vi de d t o ne w a n d e xisti n g s u bjects t hr o u g h o ut t he 
cli nical st u d y.  
T he I C F s hall al w a ys be si g ne d a n d pers o nall y date d b y t he s u bject or le g al re pres e ntati ve  
c o m pete nt t o si g n t he I C F u n der t h e a p plica ble l a ws, r ules, re g ulati o ns, a n d g ui deli nes a n d b y 
t he i n vesti gat or a n d/or a n a ut h orize d desi g n ee res p o nsi ble f or c o n d ucti n g t h e i nf or me d 
c o nse nt pr ocess. If a l e gal re prese nt ati ve si g ns, t he s u bject s hall be as ke d t o pr o vi de i nf or me d 
c o nse nt f or c o nti n ue d partici pati o n as s o o n as his/ her me dical c o n diti o n all o ws. T he ori gi nal  
si g ne d I C F will be ret ai ne d b y t he site a n d a c op y of t he si g ne d a n d dat e d d oc u me nt a n d a n y 
ot her writte n i nf or mati o n m ust be gi ve n t o t he pers o n si g ni n g t he f or m.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 8 6  of 1 0 2  
 
  
 
Fail ure t o o btai n s u bje ct c o nse nt will be re p ort e d b y B S C t o t he a p plica ble re g ulat or y 
a ut h orit y acc or di n g t o t heir re q uir e me nts (e. g., F D A re q uir e me nt is wit hi n 5 w or ki n g da ys of 
lear ni n g of s uc h a n e ve nt). A n y vi olati o ns of t he i nf or me d c o ns e nt pr ocess m ust be re p orte d 
as de viati o ns t o t he s p o ns or a n d l ocal r e g ulat or y a ut h orities ( e. g., I R B/ E C/ R E B), as 
a p pr o priate.  
 
If ne w i nf or mati o n bec o mes a vaila ble t hat ca n si g nifica ntl y affect a s u bject's f ut ure healt h 
a n d me dical c are, t h at i nf or mati o n s hall be pr o vi de d t o t he affecte d s u bject(s) i n writte n f or m 
via a re vise d I C F or, i n s o me sit uati o ns, e nr olle d s u bjects ma y be re q ueste d t o si g n a n d date 
a n a d de n d u m t o t he I C F. I n a d diti o n t o ne w si g nifica nt i nf or mati o n d uri n g t he c o urse of a 
st u d y, ot her sit uati o ns ma y necessitate re visi o n of t he I C F, s uc h as if t here are a m e n d me nts 
t o t he a p plica ble la ws, pr ot oc ol, a c ha n g e i n Pri nci pal I n v esti gat or, a d mi nistrati ve c ha n g es, or 
f oll o wi n g a n n ual re vie w b y t he I R B/ E C/ R E B. T he ne w versi o n of t h e I C F m ust be a p pr o ve d 
b y t he I R B/ E C / R E B. Acce pta nce  b y B ost o n Scie ntific is re q uire d if c h a n g es t o t he re vise d 
I C F are re q u este d b y t he site’s I R B/ E C/ R E B. T he I R B/ E C/ R E B will deter mi ne t he s u bject 
p o p ulati o n t o be re -c o ns e nte d.  
2 3.  C o m mittees  
2 3. 1.  S afety M o nit ori n g Pr ocess  
T o pr o m ote earl y d etecti o n of safet y iss ues, t he Cli nical E ve nts C o m mittee a n d Data 
M o nit ori n g C o m mittee will pr o vi de e val uati o ns of safet y e ve nts. S uccess of t his pr o gra m 
re q uires d y na mic c ollecti o n of u n m o nit ore d data as s o o n as t he e ve nt is re p orte d. D uri n g 
re g ularl y sc h e d ule d m o nit ori n g acti vities, cli nical researc h m o nit ors will s u p p ort t he d y na mic 
re p orti n g pr ocess t hr o u g h t heir re vie w of s o urce d oc u me nt a n d ot her d ata i nf or mati o n.  
 
T he B S C Me dical Safet y gr o u p i ncl u des p h ysicia ns wit h e x pertise i n electr o p h ysi ol o g y,  
i nter ve nti o nal car di ol o g y, a n d/ or car di ol o g y,  a n d wit h t he necessar y t hera p e utic a n d s u bject 
matter e x pertise t o e val u ate a n d cl assif y t he e ve nts i nt o t he cate g ories o utli ne d a b o ve.  
2 3. 2.  Steeri n g C o m mittee  
A n E xec uti ve C o m mittee c o m p ose d of t he s p o ns or's Cli nical Ma na ge me nt a n d t he st u d y 
C o or di nati n g Pri nci pal I n vesti gat or(s) ma y be c o n ve ne d. Res p o nsi bilities ma y i ncl u de 
o versi g ht of t he o verall c o n d uct of t he st u d y wit h re gar d t o pr ot o c ol de vel o p me nt, st u d y  
pr o gress, s u bject safet y, o verall data q ualit y a n d i nte grit y, a n d first li ne re vie w a n d fi nal 
decisi o n ma ki n g of i n de p e n de nt me dical r e vie wer rec o m me n dati o ns, as w ell as 
disse mi nati n g a n y st u d y res ults t hr o u g h a p pr o priate scie ntific sessi o ns a n d p u blicati o ns. 
Steeri n g  C o m mittee me m bers ma y partici pat e i n t he re vie w a n d a p pr o val of all re q uests f or 
data a nal ysis, a bstr act a n d ma n uscri pt pre parati o n, a n d s u b missi o n. As a p pr o priate, t he 
Steeri n g  C o m mittee ma y re q uest partici p ati o n of O P TI O N  I n vesti gat ors o n t he C o m mittee. 

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2 3. 3.  Cli nic al Eve nts C o m mittee  
A Cli nical E ve nts C o m mittee ( C E C) is a n i n de pe n de nt gr o u p of i n di vi d uals wit h perti ne nt 
e x pertise t hat r e vie ws a n d a dj u dicates i m p orta nt e ve nts f or i ncl usi o n i nt o t he pri mar y a n d 
sec o n dar y e n d p oi nts.  T he C E C will a dj u dicate e v e nts f or all s u bjects be gi n ni n g at t he p oi nt 
of ra n d o mizati o n.  T he e ve nts t hat t he C E C will re vie w f or t his st u d y i ncl u de:  
•  All ca use str o ke a n d TI A  
•  S yste mic e m b olis m  
•  Pericar dial Eff usi o n  re q uiri n g i nter ve nti o n 
•  A ll ca use deat h 
•  I S T H maj or blee di n g a n d cli nicall y rele va nt n o n -maj or blee di n g  
•  Ot her e ve nts, a t t he discreti o n of B ost o n Scie ntific 
 
T he C E C will re vie w a s afet y e v e nt d ossier, w hic h ma y i ncl u de c o pies of s u bject s o urce 
d oc u me nts pr o vi de d b y st u d y ce nters  a n d c o nfir m i ncl usi o n of t he e ve nt i nt o t he pri mar y a n d 
sec o n dar y e n d p oi nts.  C o m mittee me m bers hi p ma y i ncl u de practiti o ners of 
electr o p h ysi ol o g y, i nter ve nti o nal car di ol o g y, ne ur ol o g y,  a n d ne ur ora di ol o g y. C E C 
res p o nsi bilities, q ualificati o ns, me m bers hi p, a n d c o m mittee pr oce d ures are o utli ne d i n t he 
C E C c harter.  
2 3. 4.  D at a M o nit ori n g C o m mittee  
A n i n de pe n de nt D ata M o nit ori n g C o m mittee ( D M C) will be esta blis he d f or t he re vie w of 
data a n d safet y para meters i n t he st u d y.  T he D M C will de vel o p a c hart er a n d st o p pi n g r ules 
f or t he st u d y.  T he me m b ers will c o nsist of at least t hree p h ysicia ns i n s pecialties of 
electr o p h ysi ol o g y, i nter ve nti o nal car di ol o g y, or ne ur ol o g y.  At least o ne m e m ber of t he 
c o m mittee will be a bi ostatisticia n.  
 
T he D M C will f u ncti o n i n acc or da nce wit h G ui da nce f or Cli nical Tri al S p o ns ors: 
Esta blis h me nt a n d O perati o n of Cli nical Trial Data M o nit ori n g C o m mittees.  Meeti n g 
fre q ue n c y will be deter mi ne d b y t he D M C t o re vie w t he cli nical dat a a n d assess t he i m pact of 
ad verse e ve nts.  
2 4.  S us pe nsi o n or Ter mi n ati o n  
2 2 . 1 Pre m at ure Ter mi n ati o n of t he St u dy  
B ost o n Scie ntific reser ves t he ri g ht t o ter mi nate t he st u d y at a n y sta ge b ut i nte n ds t o e xercise 
t his ri g ht o nl y f or vali d scie ntific or b usi ness  reas o ns a n d reas o ns relate d t o pr otecti o n of 
s u bjects.  I n vesti gat ors, ass ociate d I R Bs/ E Cs/ R E Bs, a n d re g ulat or y a ut h orities, as a p plica ble, 
will be n otifie d i n writi n g i n t he e ve nt of st u d y ter mi nati o n. 

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2 2 . 1. 1 Criteri a f or Pre m at ure  Ter mi n ati o n of t he St u d y  
P ossi ble reas o ns f or pre mat ure st u d y ter mi nati o n i ncl u de, b ut are n ot li mite d t o, t he 
f oll o wi n g. 
•  S us pici o n of a n u nacce pt a ble ris k, i ncl u di n g seri o us healt h t hreat . I n t his case, t he 
s p o ns or s hall s us pe n d t he cli nical i n vesti gati o n w hile t he ris k is assesse d. T he s p o ns or 
s hall ter mi nate t he cli nic al i n vesti gati o n if a n u nacce pta bl e ris k w hic h ca n n ot be 
c o ntr olle d is c o nfir me d . I nstr ucti o ns b y t he I R B/ E C/ R E B or re g ulat or y a ut h orities t o 
s us pe n d or ter mi nate t he cli nical i n vesti gati o n. 
•  A n e nr oll me nt rate far bel o w e x pectati o n t hat pr ej u dices t he c o ncl usi o n of t he st u d y.  
•  A decisi o n o n t he part of B ost o n Scie ntific t o s us pe n d or disc o nti n ue de v el o p me nt of t he 
de vice.  
2 2 . 2 Ter mi n ati o n of St u dy P artici p ati o n by t he I nvesti g at or or Wit h dr a w al of I R B/ E C 
/ R E B A p pr ov al  
A n y i n vesti gat or, or ass o ciate d I R B/ E C/ R E B or re g ulat or y a ut h orit y  ma y disc o nti n ue 
partici pati o n i n t he st u d y or wit h dra w a p pr o val of t he st u d y, res pecti vel y, wit h s uita ble 
writte n n otice t o B ost o n Scie ntific.  I n vesti gat ors, ass ociate d I R Bs/ E Cs/ R E Bs, a n d re g ulat or y 
a ut h orities, as a p plica ble, will be n otifie d i n writi n g i n t he e ve nt of t hese o cc urre n ces. 
2 2 . 3. Re q uire me nts f or D oc u me nt ati o n a n d S u bject F oll o w -u p  
I n t he e ve nt of  pre mat ure st u d y ter mi nati o n, a writte n state me nt as t o w h y t he pre mat ure 
ter mi nati o n has occ urre d will  be pr o vi de d  t o all partici pati n g sites b y B ost o n Scie ntific . T he 
I R B/ E C/ R E B a n d re g ulat or y a ut h orities, as a p plica ble , will  be n otifie d. D et aile d i nf or mati o n 
o n h o w e nr olle d s u bjects will be ma na ge d t hereafter  will be pr o vi de d .  
 
I n t he e ve nt a n I R B/ E C/R E B  ter mi nates partici pati o n i n t he st u d y, partici pati n g in vesti gat ors, 
ass ociate d I R Bs/ E Cs / R E Bs, a n d re g ulat or y a ut h orities, as a p plica ble, will be n otifie d i n 
writi n g . Detaile d i nf or mati o n o n h o w e nr olle d s u bjects will be ma na ge d t h ereafter will be 
pr o vi de d b y B ost o n Scie ntific.  
 
I n t he e ve nt a Pri n ci pal I n vesti gat or ter mi nates partici pati o n i n t he st u d y, st u d y res p o nsi bilit y 
will be tra nsferre d t o a n ot her i n vesti gat or, if p ossi ble. I n t h e e ve nt t here are n o o p p ort u nities 
t o tra nsfer Pri nci pal I n vesti gat or res p o nsi bilit y; detaile d i nf or mati o n o n h o w e nr olle d 
s u bjects will be ma na ge d t hereafter will be pr o vi d e d b y B ost o n Scie ntific. 
 
T he Pri nci pal I n vesti gat or or his/ her desi g ne e m ust ret ur n all st u d y-relat e d d oc u me nts a n d 
i n vesti gati o nal pr o d uct t o B ost o n Scie ntific, u nless t his acti o n w o ul d je o par dize t he ri g hts, 
safet y, or welfare of t he s u bjects. 

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2 2 . 4 Criteri a f or S us pe n di n g/ Ter mi n ati n g a St u dy Site  
B ost o n Scie ntific reser ves t he ri g ht t o st o p t he i ncl usi o n of s u bjects at a st u d y site at a n y ti me 
after t he st u d y i nitiati o n visit if n o s u bjects ha ve bee n e nr olle d f or a p eri o d be y o n d  f o ur 
m o nt hs after site i nitiati o n, or if t he site has m ulti ple or  se vere pr ot oc ol 
vi olati o ns/ n o nc o m plia nce wit h o ut j ustificati o n a n d/ or fails t o f oll o w re me dial acti o ns.  
 
I n t he e ve nt of t er mi nati o n of site partici pati o n, all st u d y de vices a n d testi n g e q ui p me nt, as 
a p plica ble, will be ret ur n e d t o B S C  u nless t his acti o n w o ul d je o par dize t he ri g hts, safet y, or 
well -bei n g of t he s u bjects. T he  I R B/ E C/ R E B a n d re g ulat or y a ut h orities, as a p plica ble,  will  
be n otifie d . St u d y partici pa nts will be c o ntacte d, as a p plica ble, a n d b e i nf or me d of c ha n g es t o 
st u d y visit sc he d ule. 
2 5.  St u d y Re gistr ati o n a n d Res ults  
2 5. 1.  St u dy Re gistr ati o n  
T o c o m pl y wit h a p plica ble la ws a n d re g ulati o ns, t he st u d y will be re gistere d o n a p u blicl y 
accessi ble data bas e.  
2 5. 2.  Cli nic al I nvesti g ati o n Re p ort  
St u d y res ults will be ma de a vaila ble  i n acc or da nce wit h t he le gal re q uir e me nts a n d t he 
rec o g niz e d et hical pri n ci ples, i n acc or da nce wit h t he B ost o n Scie ntific P olic y. A Cli nical 
I n v esti gati o n Re p ort will be ma de a v aila ble t o all i n vesti gat ors, I R B/ E C/ R E B,  a n d re g ulat or y 
a ut h orities, as a p plica ble i n acc or da nce wit h t he B ost o n Scie ntific P olic y a n d l ocal 
re q uire me nts.  As a p plica ble a n a b bre viate d Cli nical I n v esti gati o n Re p ort will be ma de 
a vaila ble o n a p u blicl y a ccessi ble data base.  
2 6.  P u blic ati o n P olic y  
B S C re q uires discl os ure of its i n v ol ve me nt as a s p o ns or or fi na nci al s u p p orter i n a n y 
p u blicati o n or prese ntati o n relati n g t o a B S C st u d y or its res ults. B S C will s u b mit st u d y 
res ults f or p u blicati o n (re gar dless of st u d y o utc o m e) f oll o wi n g t he c o n cl usi o n or ter mi nati o n 
of t he st u d y. B ost o n Scie ntific a d heres t o t he C o ntri b ut ors hi p Criteria set f ort h i n t he 
U nif or m Re q uire me nts of t he I nter n ati o nal C o m mittee of Me dical J o ur n al E dit ors (I C MJ E; 
htt p:// w w w.ic mje. or g). I n or der t o e ns ure t he p u blic discl os ure of  st u d y res ults i n a ti mel y 
ma n ner, w hile mai ntai ni n g a n u n biase d prese ntati o n of st u d y o utc o mes, B S C pers o n nel ma y 
assist a ut h ors a n d i n vesti gat ors i n p u blicati o n pre parati o n pr o vi de d t he f oll o wi n g g ui deli nes 
are f oll o w e d :  
•  All a ut h ors hi p a n d c o ntri b ut ors hi p re q uire me nts as descri be d a b o ve m ust be f oll o we d.  

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•  B S C i n v ol ve me nt i n t he p u blicati o n pre parati o n a n d t he B S C P u blicati o n P olic y s h o ul d 
be disc usse d wit h t he C o or di nati n g Pri nci pal I n v esti gat or(s) a n d/ or E xec uti ve/ Steeri n g 
C o m mittee at t he o nset of t he pr oject.  
•  T he First a n d Se ni or a ut h ors are t he pri mar y dri v ers of decisi o ns re g ar di n g p u blicati o n 
c o nte nt, re vie w, a p pr o val, a n d s u b missi o n.  
T he data, a n al ytic met h o ds, a n d st u d y materials f or t his cli nical trial ma y  be ma de a v aila ble 
t o ot her researc h ers i n acc or da nce wit h t he B ost o n Scie ntific Data S hari n g P olic y 
(htt ps:// w w w. b ost o nscie ntific.c o m/ ).  
2 7.  Rei m b urse me nt a n d C o m pe ns ati o n f or S u bjects  
2 7. 1.  S u bject Rei m b urse me nt  
Tra vel a n d ot h er e x p e nses i nc urre d b y s u bjects as a res ult of  partici pati o n i n t he st u d y ma y  be 
rei m b urse d b y B S C, s u bject t o i ncl usi o n i n t he st u d y site’s a p pr o ve d b u d g et, a p pr o val b y t he 
st u d y site’s I R B/ E C a n d i n acc or da nce wit h perti n e nt c o u ntr y la ws a n d re g ulati o ns a n d per 
t he st u d y site’s re g ulati o ns.   
2 7. 2.  C o m pe ns ati o n f or S u bject ’s He alt h I nj ury  
B ost o n Scie ntific will p urc hase a n i ns ura n ce p olic y t o c o ver t he c ost of p ot e ntial healt h 
i nj ur y f or st u d y s u bjects, if re q uire d b y a p plica ble la w.  
2 8.  Bi bli o gr a p h y  
1.  
C olilla S, Cr o w A, Pet k u n W, Si n ger D E, Si m o n T, Li u X. Esti mates of c urre nt a n d 
f ut ure i nci de n ce a n d pre v ale nce of atrial fi brillati o n i n t he u. S. A d ult p o p ulati o n. T he 
A meric a n j o ur n al of c ar di ol o gy . 2 0 1 3; 1 1 2: 1 1 4 2-1 1 4 7  
2.  
F uster V, R y de n L E, Ca n n o m D S, Crij ns HJ, C urtis A B, Elle n b o ge n K A, et al. 
Acc/a h a/esc 2 0 0 6 g ui deli nes f or t he ma n a ge me nt of patie nts wit h atrial fi brillati o n --
e xec uti ve s u m mar y: A re p ort of t he a meri ca n c oll e ge of car di ol o g y/a meri ca n heart 
ass ociati o n tas k f orce o n practice g ui d eli nes a n d t he e ur o pea n s ociet y of car di ol o g y 
c o m mittee f or practice g ui deli nes ( writi n g c o m mittee t o re vise t he 2 0 0 1 g ui deli nes 
f or t he ma na g e me nt of p atie nts wit h atrial fi brillati o n). J A m C oll C ar di ol . 
2 0 0 6; 4 8: 8 5 4 -9 0 6  
3.  
C o n n oll y SJ, P o g ue J, Ei kel b o o m J, Fla ker G, C o m merf or d P, Fra nz osi M G, et al. 
Be nefit of oral a ntic oa g ula nt o ver a nti platelet t hera p y i n atrial fi brillati o n de pe n ds o n 
t he q ualit y of i nter nati o nal n or malize d rati o c o ntr ol ac hie ve d b y ce nters a n d c o u ntries 
as meas ure d b y ti me i n t hera pe utic ra n g e. Circ ul ati o n . 2 0 0 8; 1 1 8: 2 0 2 9-2 0 3 7  
4.  
Hart R G, Pearce L A, M c Bri de R, R ot h bart R M, Asi n ger R W. Fact ors ass o ciate d wit h 
isc he mic str o ke d uri n g as piri n t hera p y i n atrial fi brillati o n: A nal ysis of 2 0 1 2 
partici pa nts i n t he s paf i -iii cli nical trials. T he str o ke pre ve nti o n i n atri al fi brillati o n 
(s paf) i n vesti gat ors. Str o ke . 1 9 9 9; 3 0: 1 2 2 3-1 2 2 9  

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           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 9 1  of 1 0 2  
 
  
5.  
W hite H D, Gr u b er M, Fe yzi J, Kaatz S, Tse H F, H uste d S, et al. C o m paris o n of 
o utc o mes a m o n g patie nts ra n d o mize d t o warfari n t hera p y acc or di n g t o a ntic oa g ula nt 
c o ntr ol: Res ults fr o m s p ortif iii a n d v. Arc h I nter n Me d . 2 0 0 7; 1 6 7: 2 3 9-2 4 5  
6.  
Fal k, R H. Et h nic Dis parit y i n I ntracra ni al He m orr ha ge a m o n g A ntic o a g ulate d 
Patie nts Wit h A F. J A m C oll Car di ol. 2 0 0 7; 5 0( 4): 3 1 6 -3 1 8  
7 . 
C o n n oll y SJ, Eze k o witz M D, Y us uf S, Ei kel b o o m J, Ol d gre n J, Pare k h A, et al. 
Da bi gatra n v ers us warfari n i n patie nts wit h atrial fi brillati o n. T he Ne w E n gl a n d 
j o ur n al of me dici ne. 2 0 0 9; 3 6 1: 1 1 3 9-1 1 5 1  
8 . 
C o n n oll y SJ, Eze k o witz M D, Y us uf S, Reill y P A, Walle nti n L. Ne wl y i de ntifie d 
e ve nts i n t he re-l y tri al. T he Ne w E n gl a n d j o ur n al of me dici ne . 2 0 1 0; 3 6 3: 1 8 7 5-1 8 7 6  
9 . 
Hart R G, Die ner H C, Ya n g S, C o n n oll y SJ, Walle nti n L, Reill y P A, et al. I ntracra nial 
he m orr ha g e i n atrial fi brillati o n patie nts d uri n g a ntic oa g ulati o n wit h warfari n or 
da bi gatra n: T he re -l y trial. Str oke . 2 0 1 2; 4 3: 1 5 1 1-1 5 1 7  
1 0 . 
F D A Dr u g Safet y C o m m u nicati o n: U p date o n t he ris k f or seri o us blee di n g e ve nts 
wit h t he a ntic oa g ula nt Pra da xa ( da bi gatra n) F D S C. 
htt p:// w w w.f d a. g ov/ Dr u gs/ Dr u g S afety/ uc m 3 2 6 5 8 0. ht m .  
1 1 . 
Patel M R, Ma haffe y K W, Gar g J, Pa n G, Si n ger D E, Hac ke W, et al. Ri var o xa ba n 
vers us warfari n i n n o n val v ular atrial fi brillati o n. T he Ne w E n gl a n d j o ur n al of 
me dici ne . 2 0 1 1; 3 6 5: 8 8 3-8 9 1  
1 2 . 
Gra n ger C B, Ale xa n der J H, Mc M urra y JJ, L o p es R D, H yle k E M, Ha n na M, et al. 
A pi xa ba n vers us warfari n i n patie nts wit h atrial fi brillati o n. T he Ne w E n gl a n d j o ur n al 
of me dici ne . 2 0 1 1; 3 6 5: 9 8 1-9 9 2  
1 3 . 
Gi u glia n o R P, R uff C T, Bra u n wal d E, M ur p h y S A, Wi vi ott S D, Hal peri n J L, et al. 
E d o xa ba n vers us warfari n i n patie nts wit h atrial fi brillati o n. T he Ne w E n gl a n d 
j o ur n al of me dici ne. 2 0 1 3; 3 6 9: 2 0 9 3-2 1 0 4  
1 4 . 
Re d d y V Y, D os hi S K, Sie vert H, B uc h bi n der M, Ne uzil P, H u ber K, et al. 
Perc uta ne o us left atrial a p pe n da ge cl os ure f or str o ke pr o p h yla xis i n patie nts wit h 
atrial fi brillati o n: 2. 3 -year f oll o w -u p of t he pr otect af ( watc h ma n left atrial a p pe n da g e 
s yste m f or e m b olic pr ote cti o n i n patie nts wit h atrial fi brillati o n) trial. Circ ul ati o n . 
2 0 1 3; 1 2 7: 7 2 0 -7 2 9  
1 5 . 
R h yt h m H. T he heart r h yt h m s ociet y’s 3 4t h a n n ual scie ntific sessi o ns. 2 0 1 3  
1 6 . 
Re d d y V Y, H ol mes D, D os hi S K, Ne uzil P, Kar S. Safet y of perc uta ne o us l eft atrial 
a p pe n da g e cl os ure: Res ults fr o m t he watc h ma n left atrial a p pe n da g e s yste m f or 
e m b olic pr otecti o n i n patie nts wit h af ( pr otect af) cli nical trial a n d t he c o nti n ue d 
access registr y. Circ ul ati o n . 2 0 1 1; 1 2 3: 4 1 7-4 2 4  
1 7 . 
Re d d y V. Y. et al. Left Atrial A p pe n da ge Cl os ur e Wit h t he Watc h ma n De vice i n 
Patie nts Wit h a C o ntrai n dicati o n f or Oral A ntic oa g ulati o n. T he A S A P St u d y ( A S A 
Pla vi x Feasi bilit y St u d y Wit h Watc h ma n L eft Atrial A p pe n da ge Cl os ure 
Tec h n ol o g y). J A m C oll Car di ol 2 0 1 3; 6 1: 2 5 5 1 -6  
1 8.       H ol mes D R, Jr., Kar S, Price MJ, W hise n a nt B, Sie vert H, D os hi S K, et al. 
Pr os pecti ve ra n d o mize d e val uati o n of t he watc h m a n left atrial a p p e n da g e cl os ure 
de vice i n patie nts wit h atrial fi brillati o n vers us l o n g -ter m warfari n t hera p y: T he 
pre vail trial. J A m C oll C ar di ol . 2 0 1 4; 6 4: 1-1 2  

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1 9 . 
Re d d y V. Y.et al. 5 Y ear O utc o mes After Left Artrial A p pe n da g e Cl os ure: Fr o m t he 
P R E V AI L a n d P R O T E C T A F Tri als. J A m C oll Car di ol 2 0 1 7; 7 0 ( 2 4): 2 9 6 4 -2 9 7 5  
2 0.   
H ol mes D R et al. Left Atrial A p pe n da g e Cl os ure as a n Alter nati ve T o War fari n f or 
Str o ke Pre ve nti o n i n Atrial Fi brillati o n: A Patie nt -Le vel Meta -A nal ysis . J A m C oll 
C ar di ol . 2 0 1 5; 6 5:2 6 1 4 -2 6 2 3  
2 1.  
B oers ma L, Sc h mi dt B, Betts T, Sie vert H, Ta m b uri n o C, Tei ger E, Stei n K,     
Ber g ma n n M.  E W O L U TI O N: Desi g n of a Re gi str y t o E val uate Real -W orl d Cli nical 
O utc o mes i n Patie nts Wit h A F a n d Hi g h Str o ke Ris k -Treate d Wit h t he 
W A T C H M A N Left Atrial A p pe n da ge Cl os ure T ec h n ol o g y. Cat heterizati o n a n d 
Car di o vasc ular I nter ve nti o ns 0 0: 0 0 – 0 0 ( 2 0 1 5).  D OI: 1 0. 1 0 0 2/cc d. 2 6 3 5 8.  
2 2.  
B oers ma L., Peri -pr oce d ural Safet y of Left Atrial A p pe n da ge Occl usi o n wit h t he 
W A T C H M A N D e vice. Preli mi nar y Data Fr o m t he E W O L U TI O N Re gistr y –  
Prese nte d at A H A 2 0 1 5  
2 3.  
Ber g ma n n, M. W., E W O L U TI O N: 3 -m o nt hs o utc o me of left atrial a p pe n d a ge cl os ur e 
wit h t he W A T C H M A N de vice i n E ur o pe. - Prese nte d at E ur o P C R 2 0 1 6  
2 4.  
P hilli ps K P, Sa nt os o T, Sa n ders P, et al. Left atrial a p pe n da g e cl os ure wit h 
W A T C H M A N i n Asia n patie nts: 2 year o utc o mes fr o m t he W A S P re gistr y. IJ C Heart 
& Vasc ulat ure. 2 0 1 9; 2 3: 1 0 0 3 5 8.  
2 5.  
Var os y P et al. Pr oce d ural Safet y of Wat c h ma n I m pla ntati o n: T he U S N E S T E D P ost 
A p pr o val St u d y. J A C C Marc h 2 0, 2 0 1 8. V ol u me 7 1, Iss u e 1 1.  
2 6.   
A o n u ma K. et al. Efficac y a n d Safet y of Left Atri al A p pe n da g e Cl os ure Wit h 
W A T C H M A N i n Ja pa n ese N o n val v ular Atrial Fi brillati o n Patie nts. Fi nal 2 -Year 
F oll o w -u p O utc o me Data Fr o m t he S A L U T E Trial. Circ J 2 0 2 0; 8 4: 1 2 3 7 -1 2 4 3  
2 7.   
Kar S. et al. Pri mar y O ut c o me E val uati o n of a Ne xt -Ge nerati o n Left Atrial 
A p pe n da ge Cl os ur e De vi ce: Res ults Fr o m t he PI N N A C L E F L X Trial. Circ ulati o n 
2 0 2 1 Ma y 4; 1 4 3 ( 1 8); 1 7 5 4 -1 7 6 2.  
2 8.  
Fri ber g L, R ose n q vist M, Li p G Y. E val uati o n of ris k stratificati o n sc he mes f or 
isc hae mic str o ke a n d ble e di n g i n 1 8 2 6 7 8 patie nts wit h atrial fi brillati o n: T he s we dis h 
atrial fi brillati o n c o h ort st u d y. E ur. Heart J. 2 0 1 2; 3 3: 1 5 0 0 -1 5 1 0  
2 9.  
Ja n uar y C T, Wa n n L S, Cal ki ns H, Fiel d M E, C he n L Y, F urie K L, et al. 2 0 1 9 
A H A/ A C C/ H R S F oc use d U p date of t he 2 0 1 4 A H A/ A C C/ H R S G ui deli ne f or t he 
Ma na ge me nt of Patie nts Wit h Atrial Fi brillati o n, Heart R h yt h m ( 2 0 1 9), d oi: 
htt ps:// d oi. or g/ 1 0. 1 0 1 6/j. hrt h m. 2 0 1 9. 0 1. 0 2 4  
3 0.  
H i n dric ks G, P ot para T, Da gres N, Ar bel o E, Ba x JJ, et al. 2 0 2 0 E S C G ui deli ne f or 
t he dia g n osis a n d ma na g e me nt of atrial fi brillati o n de vel o pe d i n c olla b orati o n wit h 
E ur o pea n Ass o ciati o n f or Car di o -T h oracic S ur ge y ( E A C T S) , E ur o pea n Heart J o ur nal 
( 2 0 2 0) 4 2, 3 7 3-4 9 8 d oi: 1 0. 1 0 9 3/e ur heartj/e haa 6 1 2  
 
 

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2 9.  A b bre vi ati o ns a n d Defi niti o ns  
2 9. 1.  A b brevi ati o ns  
A b bre viati o ns are s h o w n i n  T a ble 2 9. 1 -1 . 

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T a ble 2 9. 1 -1 : A b bre vi ati o ns 
A b bre vi ati o n  
Ter m  
A D E  
A d verse De vice Effect  
A E  
A d verse E ve nt  
A F  
Atrial Fi brillati o n  
B S C  
B ost o n Scie ntific C or p orati o n  
C F A E (a blati o n)  
C o m ple x Fracti o nate d Atrial Electr o gra ms  
CI P  
Cli nical I n vesti gati o n Pla n  
C H F  
C o n gesti ve Heart Fail ure  
C N S  
Ce ntral Ner v o us S yste m  
C R F  
Case Re p ort F or m  
C R O  
C o ntract Researc h Or ga nizati o n  
C T  
C o m p uterize d T o m o gra p h y  
C TI (a blati o n)  
Ca v o -Tric us pi d Ist h m us  
D A P T  
D ual A nti platelet T hera p y  
D F U  
Directi o ns f or Use  
D O A C  
Direct Oral A ntic oa g ula nt (see N O A C)  
E C  
Et hics C o m mittee  
F M E A  
Fail ure M o de Effects   
F U  
F oll o w -u p  
GI  
Gastr oi ntesti nal  
H A  
Hazar d A nal ysis   
H A T  
H y patte n uate d t hic ke ni n g  
I C E 
I ntra-C ar diac Ec h o  
I C F 
I nf or me d C o nse nt F or m 
I F U 
I nstr ucti o n f or Use  
I R B 
I nstit uti o nal Re vie w B oar d 
L A A  
Left Atrial A p pe n da ge  
L V E F  
Left Ve ntric ular Ejecti o n Fracti o n  
MI  
M y ocar dial I nfarcti o n  
M R S  
M o difie d Ra n ki n Scale  
NI  
N o n -I nferi or 
NI H S S  
Nati o nal I nstit utes of Healt h Str o ke Scale   
( N) O A C 
( N o n-V K A) Oral A ntic oa g ula nt  (see D O A C) 
P F O  
Pate nt F ora me n O vale  
P D L  
Peri -De vice Lea k  
Q o L  
Q ualit y of Life  
S A D E  
Seri o us A d verse De vice Effect  
S A E  
Seri o us A d verse E ve nt  
S E  
S yste mic E m b olis m  
T E E  
Tra nses o p ha geal Ec h o  
T T E  
Tra ns T h oracic Ec h o  
TI A  
Tra nsie nt Isc he mic Attac k  

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V K A  
Vita mi n K A nta g o nist  
W M  
W A T C H M A N  
 
 
 
 

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2 9. 2.  Defi niti o ns  
2 9. 2. 1.  V al v ul ar Atri al Fi brill ati o n  
Atrial fi brillati o n i n t he setti n g of m o derate -t o-se v ere mitral ste n osis ( p ote ntiall y re q uiri n g 
s ur gical i nter ve nti o n) or i n t he prese n ce of a n artifi cial ( mec h a nical) h eart v al ve .  
2 9. 2. 2.  N o n -V al v ul ar Atri al Fi brill ati o n  
A trial fi brillati o n i n t he a bse nce of m o d erate-t o-se vere mitral ste n osis or a mec ha nical heart 
val ve . 
2 9. 2. 3.  Blee di n g defi niti o ns  
2 9. 2. 3. 1.  Blee di n g Aca de mic R esearc h C o ns orti u m ( B A R C ) 
T y pe 0:   
N o  blee di n g   
T y pe 1:   
Blee di n g t hat is n ot acti o na ble a n d d oes n ot ca use t he s u bject t o see k u nsc he d ule d 
perf or ma n ce of st u dies, h os pitalizati o n, or treat me nt b y a healt h -care pr ofessi o nal; ma y 
i ncl u de e pis o des le a di n g t o self-disc o nti n uati o n of me dical t hera p y b y t he s u bject 
wit h o ut c o ns ulti n g a healt h -care pr ofessi o nal.   
 
T y pe 2:   
A n y o vert, acti o na ble si g n of  he m orr ha g e (e. g., m ore  blee di n g t ha n w o ul d be e x pecte d 
f or a cli nical cir c u msta nce, i ncl u di n g blee di n g f o u n d b y i ma gi n g al o ne) t h at d oes n ot 
fit t he criteria f or t y pe 3, 4, or 5 b ut d oes meet at l east o ne of t he f oll o wi n g criteria:  
•  
re q uiri n g 
n o ns ur gical, 
me dical i nter ve nti o n 
b y 
a 
healt h-car e 
pr ofessi o nal,   
•  
lea di n g t o h os pitalizati o n or i ncrease d le vel of care, or  
•  
pr o m pti n g e val uati o n   
T y pe 3:   
T y pe 3a:   
•  
O vert  blee di n g  pl us  he m o gl o bi n  dr o p of 3 t o < 5 g/ d L( pr o vi de d  
he m o gl o bi n dr o p is relate d t o blee d)   
•  
A n y tra nsf usi o n wit h o vert blee di n g   
T y pe 3 b:   
•  
O vert  blee di n g  pl us  he m o gl o bi n  dr o p ≥5 g/ d L( pr o vi de d he m o gl o bi n  
        dr o p is relate d t o blee d),   
•  
Car diac ta m p o na d e,   
•  
Blee di n g re q uiri n g s ur gical i nter ve nti o n f or c o ntr ol (e xcl u di n g  
       de ntal/ nasal/s ki n/ he m orr h oi d),   
•  
Blee di n g re q uiri n g i ntra v e n o us vas oacti ve a ge nts   
 
 

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T y pe 3c:   
•  
I ntr acra nial he m orr ha ge ( d oes n ot i ncl u de micr o bl ee ds or he m orr ha gic 
        tra nsf or mati o n, d oes i ncl u de i ntras pi nal),  
•  
S u bcate g ories c o nfir me d b y a ut o ps y or i ma gi n g or l u m bar p u nct ure,   
•  
I ntr a oc ular blee d c o m pr o misi n g visi o n.   
     T y pe 4:   
•  
C A B G -relate d blee di n g,  
•  
Peri o perati ve i ntracra nial blee di n g  wit hi n 4 8 h,   
•  
Re o perati o n after cl os ur e of ster n ot o m y f or t h e p ur p ose of c o ntr olli n g     
blee di n g   
•  
Tra nsf usi o n of ≥ 5 U w h ole bl o o d or p ac ke d re d bl o o d cells wit hi n a 4 8 -
h peri o d,   
•  
C hest t u be o ut p ut m ore t ha n or e q ual t o 2 L wit hi n a 2 4 -h peri o d   
          T y pe 5:   
Fatal ble e di n g   
    T y pe 5a:   
Pr o ba ble fatal ble e di n g; n o a ut o ps y or i ma gi n g c o nfir mati o n b ut cli nicall y  
s us pici o us  
    T y pe 5 b:   
Defi nite fat al blee di n g; o vert blee di n g or a ut o ps y or i ma gi n g c o nfir mati o n   
  
(fr o m Circ ul ati o n . 2 0 1 1; 1 2 3 ( 2 3): 2 7 3 6-4 7)   
  
F or t he p ur p os es of t he O P TI O N trial, a B A R C sc ore of T y p e 3 a, b, c a n d 5 a a n d b will be 
c o nsi dere d a maj or blee di n g e ve nt.   
 
2 9. 2. 3. 2.  I S T H 
I nter nati o nal S ociet y o n T hr o m b osis a n d Hae m ostasis blee di n g defi niti o ns. 
I S T H Cli nical r ele va nt n o n-maj or blee di n g is defi ne d as a n y si g n or s y m pt o m of he m orr ha g e 
(e. g., m ore ble e di n g t ha n w o ul d be e x pecte d f or a cli nical circ u msta nce, i ncl u di n g blee di n g 
f o u n d b y i ma gi n g al o ne) t hat d oes n ot fit t he criteria f or t he I S T H d efi niti o n of maj or 
blee di n g b ut d oes meet at least o ne of t he f oll o wi n g criteria 1. 
 
•  
re q uiri n g me dical i nter v e nti o n b y a healt hcare pr ofessi o nal  
•  
lea di n g t o h os pitalizati o n or i ncrease d le vel of care (e. g., E R visit, dia g n ostic 
pr oce d ures, me dicati o n c ha n ge)  
•  
pr o m pti n g a face t o face  *  (i.e., N ot j ust a tele p h o ne or electr o nic c o m m u nicati o n) 
e val uati o n  
*s uc h as offic e or tele h ealt h visit t o e val uate t he e ve nt 
 
 
 

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I S T H maj or blee di n g is d efi ne d as h a vi n g a s y m pt o matic prese ntati o n a n d2. 
•  
Fatal ble e di n g, a n d/ or  
•  
Blee di n g i n a critical area or or ga n, s u c h as i ntracra nial, i ntras pi nal, i ntra o c ular, 
retr o perit o neal, i ntraartic ular, or peri car di al, or i ntra m usc ular wit h c o m p art me nt 
s y n dr o me, a n d/ or 
•  
Blee di n g ca usi n g a fall i n he m o gl o bi n le vel of 2 0 g L -1 ( 1. 2 4 m m ol L-1) or m ore or  
lea di n g t o tra nsf usi o n of t w o or m ore u nits of w h ole bl o o d or re d cells.  
 
1.  
K aatz S, A h ma d D, et al. Defi niti o n of cli nicall y rele va nt n o n -maj or blee di n g i n st u dies of a ntic oa g ula nts i n atrial fi brillati o n a n d 
ve n o us t hr o m b oe m b olic disease i n n o n-s ur gical patie nts. J T hr o m b Hae m ost  2 0 1 5; 1 3: 2 1 1 9 -2 6. 
2.  
Sc h ul ma n S, Kear o n C, et al. Defi niti o n of maj or blee di n g i n cli nical i n vesti gati o ns of a nti he m ostatic me dici nal pr o d ucts i n n o n -
s ur gical patie nts. J T hr o m b Hae m ost 2 0 0 5; 3: 6 9 2– 4. 
2 9. 2. 4.  C ar di ac Perf or ati o n  
A pericar dial eff usi o n res ulti n g i n s ur gical i nter ve nti o n/re pair, re g ar dless of w het her i nitial 
atte m pts at n o n -i n vasi ve or perc ut a ne o us w ere atte m pte d. 
2 9. 2. 5.  Left Ve ntric ul ar ( L V) D ysf u ncti o n  
As part of t he e val uati o n of s u bjects C H A D S -V A Sc  sc ore a n d s yst olic d ysf u ncti o n, 
refere nci n g E S C 2 0 2 0 G ui deli nes ( Ta ble 8)3 0  bel o w is a refere n ce t o L V d ysf u ncti o n 
t hres h ol ds  
 
•  
Se vere L V D ysf u ncti o n: < 3 5 %  
•  
M o derate L V D ysf u ncti o n: 3 5 -4 0 %  
•  
Mil d L V D ysf u ncti o n: 4 1 -4 9 %  
•  
N or mal L V D ysf u n cti o n: >  5 0 %  
 
E ur o pea n J o ur nal of Heart Fail ure ( 2 0 1 2) 1 4, 2 9 5 – 3 0 1  d oi: 1 0. 1 0 9 3/e urj hf/ hfs 0 0 5  
 
2 9. 2. 6.  M ort alit y  
C ar di o v asc ul ar De at h  
•  
Deat h d ue t o pr o xi mate car diac ca use, e. g., m y ocar dial i nfarcti o n, car diac ta m p o na de, 
w orse ni n g heart fail ure, e n d ocar ditis;  
•  
Deat h ca use d b y n o n -c or o nar y, n o n -C N S vasc ular c o n diti o ns s uc h as p ul m o nar y 
e m b olis m, r u pt ure d a ortic a ne ur ys m, dissecti n g a ne ur ys m, or ot her vasc ular disease;  
•  
Deat h fr o m vasc ular C N S ca uses  
o  Fr o m hae m orr ha gic str o ke  
o  Fr o m isc hae mic str o ke  
•  
All -ca use m ortalit y d uri n g t he i n de x pr oce d ure, a n y pr oce d ure -relate d deat h wit hi n 3 0 
da ys after t he i n de x pr oce d ure or d uri n g p ost o perati ve h os pitalizati o n f or t he i n de x 
pr oce d ure (if > 3 0 da ys). T hese i ncl u di n g t h ose relate d t o a c o m plicati o n of t he pr oce d ure 
or treat me nt f or a c o m plicati o n of t he pr oce d ure.  

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U ne x pl ai ne d De at h  
•  
S u d de n or u n wit nesse d d eat h defi ne d as n o n -tr a u matic, u ne x pecte d fatal e ve nt 
occ urri n g wit hi n o ne h o ur of t he o nset of s y m pt o ms i n a n a p pare ntl y healt h y s u bject. 
If deat h is n ot wit nesse d, t he defi niti o n a p plies w h e n t he victi m was i n g o o d healt h 2 4 
h o urs bef ore t he e v e nt.  
•  
Deat h of u n k n o w n ca use.  
 
N o n -C ar di o v asc ul ar De at h  
A n y deat h i n w hic h t he pri mar y ca us e of deat h is clearl y relate d t o a n ot her c o n diti o n ( e. g., 
tra u ma, ca n cer, s uici de).  
 
Peric ar di al Eff usi o n  
Se verit y of pericar dial eff usi o n, wit h or wit h o ut car diac ta m p o n a de, is defi ne d b y t he cli nical 
t hera p y ass oci ate d wit h t he eff usi o n 1:  
 
Cli nic ally n o n -relev a nt  
•  
Re q uiri n g n o i nter ve nti o n  
•  
Treate d p h ar mac ol o gicall y  
 
Cli nic ally relev a nt  
•  
Treate d wit h t hera pe utic pericar di oce ntesis  
•  
Treate d wit h s ur gical i nter ve nti o n  
•  
Re q uiri n g bl o o d tra nsf usi o n  
•  
Res ulti n g i n s h oc k a n d/ or deat h  
1 Tzi kas et al. Perc uta ne o us left atrial a p pe n da ge occl usi o n: t he M u nic h c o nse ns us d oc u me nt o n defi niti o ns, e n d p oi nts, a n d data c ollecti o n 
re q uire me nts f or cli nical st u dies. E ur o pace. 2 0 1 7 Ja n; 1 9( 1): 4 -1 5.  
 
2 9. 2. 7.  Str o ke/ TI A defi niti o ns  
Br oa d defi niti o ns:  
Ne ur ol o gic al deficit:  A n ac ute e pis o de of a f ocal or gl o bal ne ur ol o gical d eficit wit h at least 
o ne of t he f oll o wi n g:  
•  
C ha n ge i n t he le vel of c o nsci o us ness  
•  
He mi ple gia  
•  
He mi paresis  
•  
O ne -si de d n u m b ness or s e ns or y l oss 
•  
D ys p hasia or a p h asia  
•  
He mia n o pia  
•  
A ma ur osis f u ga x  
•  
A n y ot her ne ur ol o gical si g ns or s y m pt o ms c o nsiste nt wit h str o ke  
 

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I n a d diti o n, t here are n o ot her rea dil y i de ntifia ble n o n-str o ke ca us e f or t he cli nical prese ntati o n 
(e. g., brai n t u m or, tra u ma, i nfecti o n, h y p o gl yce mia, peri p heral lesi o n, p har mac ol o gic 
i nfl ue nces), t o be d eter mi ne d b y or i n c o nj u ncti o n wit h t he desi g nate d ne ur ol o gist.  
 
Str o ke : Str o ke is defi ne d b y eit her o ne of t h e f oll o wi n g: 
•  D urati o n of f ocal or gl o b al ne ur ol o gical deficit > 2 4 h.  
•  D urati o n of f ocal or gl o bal ne ur ol o gical deficit < 2 4 h i n case of i ma gi n g -
d oc u me nte d ne w h e m orr ha ge or i nfarct.  
•  A ne ur ol o gical deficit res ulti n g i n deat h.   
 
Tr a nsie nt isc he mic att ac k:  A TI A is defi ne d b y a n y ne ur ol o gical deficit n ot satisf yi n g t he 
a b o ve criteria f or str o k e, s pecificall y a d eficit lasti n g < 2 4 h wit h o ut i ma gi n g -d oc u me nte d ne w 
he m orr ha g e or i nfarct.  
 
Str o ke dia g n ostic criteria:  
•  
Ra pi d o nset of a f ocal or gl o bal ne ur ol o gical deficit wit h at least o ne of t he 
f oll o wi n g: c ha n ge i n le vel of c o nsci o us ness, h e mi ple gia, he mi paresis, n u m b ness or 
se ns or y l oss affecti n g o ne si de of t he b o d y, d ys p hasia or a p hasia, hae mi a n o pia, 
a ma ur osis f u ga x , or ot her ne ur ol o gical si g ns or s y m pt o ms c o nsiste nt wit h str o ke;  
•  
D urati o n of a f ocal or gl o bal ne ur ol o gical defi cit ≥2 4 h; O R, 2 4 h, if t hera pe utic 
i nter ve nti o n(s) 
w ere p erf or me d (e. g. t hr o m b ol ytic t hera p y or i ntracra ni al 
a n gi o plast y); O R a vaila ble ne ur oi ma gi n g d oc u me nts a ne w he m orr ha ge or i nfarct; 
O R t he ne ur ol o gical deficit res ults i n deat h  
•  
N o ot her rea dil y i de ntifi a ble n o n -str o ke ca us e f or t he cli nical prese ntati o n (e. g. 
brai n t u m or, tra u ma, i nfecti o n, h y p o gl yce mia, peri p heral lesi o n, p har mac ol o gical 
i nfl ue nces) 
•  
C o nfir mati o n of t he dia g n osis b y at least o ne of t h e f oll o wi n g:  
o  Ne ur ol o g y or ne ur os ur gi cal s pecialist  
o  Ne ur oi ma gi n g pr oce d ure ( M R or C T sca n or cere bral a n gi o gra p h y)  
o  L u m bar p u nct ure (i.e. s pi nal fl ui d a nal ysis dia g n ostic of i ntracra nial 
he m orr ha g e)  
Str o ke T y pes:  
Isc he mic: A n e pis o de of ne ur ol o gical d ysf u ncti o n ca use d b y f o cal cere bral, s pi nal, or reti nal  
i nfarcti o n 
He m orr h a gic:  
•  
i ntracere bral: ra pi dl y d e vel o pi n g cli nical si g ns of ne ur ol o gical d ysf u ncti o n 
attri b uta ble t o a f ocal c ollecti o n of bl o o d wit hi n t he brai n pare nc h y m a or v e ntric ular 
s yste m t hat is n ot ca use d b y tra u ma. 
•  
S u barac h n oi d: ra pi dl y de vel o pi n g si g ns of ne ur ol o gical d ysf u ncti o n a n d/ or 
hea dac he beca use of blee di n g i nt o t he s u barac h n oi d s pace (t he s p ace bet wee n t he 
arac h n oi d me m bra ne a n d t he pia mater of t he brai n or s pi nal c or d), w hic h is n ot 
ca use d b y tr a u ma.  
•  
N O T E: he m orr h a gic tra nsf or mati o n of a k n o w n is c he mic str o ke will be c o nsi dere d 
a n isc he mic str o ke.  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 0 1  of 1 0 2  
 
  
Sile nt i nf arcti o n: I ma gi n g or ne ur o pat h ol o gical e vi de nce of C N S i nfarcti o n, wit h o ut a hist or y 
of ac ute n e ur ol o gical d ysf u ncti o n attri b uta ble t o t he lesi o n.  
 
Str o ke c a use d by cer e br al ve n o us t hr o m b osis: I nfarcti o n or h e m orr ha g e i n t he brai n, s pi nal 
c or d, or reti na b eca us e of t hr o m b osis of a cere bral ve n o us str uct ure. S y m pt o ms or si g ns ca use d  
b y re versi ble e de ma wit h o ut i nfarcti o n or he m orr ha ge d o n ot q ualif y as str o ke.  
 
N ot ot her wise s pecifie d: a n e pis o de of ac ute ne ur ol o gical d ysf u ncti o n pres u me d t o be ca use d 
b y isc he mia or he m orr ha ge, persisti n g ≥ 2 4 h o urs or u ntil deat h, b ut wit h o ut s ufficie nt 
e vi de nce t o b e classifie d as o ne of t he a b o ve  
(fr o m Ka p petei n, A. P., et al., J A m C oll Car di ol, 2 0 1 2. 6 0 ( 1 5): p. 1 4 3 8-5 4) 
 
Dis a bli n g str o ke:  
a n m R S sc ore of 2 or m ore at 9 0 da ys a n d a n i ncrease i n at least o ne m R S cate g or y fr o m a n 
i n di vi d ual’s pre-str o ke b aseli ne 
 
N o n -dis a bli n g str o ke:  
a str o ke t hat res ults ( at 9 0 da ys after  str o ke o nset) i n a n m R S sc ore of  >  2 , or t hat d oes n ot 
res ult i n a n i ncrease i n ≥1 m R S cate g or y fr o m a n i n di vi d ual's pre-str o ke baseli ne  
 
2 9. 2. 8.  S yste mic E m b olis m  
Ac ute vasc ul ar i ns uffici e nc y or occl usi o n of t he e xtre mities or a n y n o n -C N S or ga n 
ass ociate d wit h cli nical, i ma gi n g, s ur gical/a ut o ps y e vi de nce of art erial occl usi o n i n t he 
a bse nce of ot her li kel y m ec ha nis m (e. g., tr a u ma, at her oscler osis, or i nstr u m e ntati o n ). W he n 
t here is pres e nce of pri or peri p heral arter y disease, a n gi o gra p hic or s ur gical or a ut o ps y 
e vi de nce is r e q uire d t o s h o w a br u pt art erial occl usi o n.  
2 9. 2. 9.   Pr oce d ure rel at e d C o m plic ati o ns  
T he occ urre n ce of o ne of t he f oll o wi n g e ve nts bet wee n t he ti me of i m pla nt a n d wit hi n 7 
da ys  f oll o wi n g t he pr oce d ure or b y h os pital disc h ar ge, w hic h e ver is later:  
•  
All -ca use d eat h   
•  
Is c he mic str o ke  
•  
S yste mic e m b olis m, or   
•  
De vice - or pr oce d ure -relate d e ve nts r e q uiri n g o pe n car diac s ur ger y or maj or 
e n d o vasc ular i nter ve nti o n s uc h as pse u d oa n e ur ys m re pair, A V fist ula re pair,   
or ot her maj or e n d o v asc ular re p air.    
  
N ote:  Perc uta ne o us cat heter drai na ge of pericar dial eff usi o ns, s nari n g of a n e m b olize d 
de vice, t hr o m bi n i njecti o n t o treat fe m or al pse u d o a ne ur ys m a n d n o ns ur gi cal treat me nts of 
access site c o m plicati o ns are e x cl u de d fr o m t his  defi niti o n  

C o nfi de ntial  
F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A P  
            
    
 
    
           O P TI O N Pr ot oc ol, d oc u me nt # 9 2 3 2 0 9 5 5 , Re v E 
Pa ge 1 0 2  of 1 0 2  
 
  
2 9. 2. 1 0.  Or al A ntic o a g ul a nt C o m pli a nce  
Patie nts w h o are o n N O A C > 8 0 % of t he ti me will be c o nsi dere d as bei n g c o m plia nt t o O A C 
t hera p y.