The Medtronic Harmony™ Transcatheter Pulmonary Valve Clinical Study
Phase: NA
Conditions: Congenital Heart Disease, Tetrology of Fallot, RVOT Anomaly, Pulmonary Regurgitation
Sponsor: Medtronic Heart Valves

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1  of 1 2 1  
 
 
 
 
Cli nic al I n v esti g ati o n Pl a n  
Cli nic al I n v esti g ati o n Pl a n/ St u d y Titl e T h e M e dtr o nic H ar m o ny ™ Tr a nsc at h et er 
P ul m o n ar y V al v e C li nic al St u dy 
Cli nic al I n v esti g ati o n Pl a n I d e ntifi er  M D T 1 6 0 0 4 C O N 0 0 1  
St u d y Pr o d uct N a m e  H ar m o ny Tr a nsc at h et er P ul m o n ary V alv e a n d 
D eliv er y S yst e m  
S p o ns or/L oc al S p o ns or  Gl o b al S p o ns or: 
M e dtr o nic  
C or o n ary a n d Str uct ur al H e art Cli nic al 
8 2 0 0 C or al S e a St N E,  M V S 6 6 
M o u n ds Vi e w, M N  5 5 1 1 2  
U nit e d St at es  
 
 
 
 
 
 
 
 
 
 
 
D oc u m e nt V ersi o n  6. 0  
V ersi o n D at e  1 2J U N 2 0 1 9  
L e a d Pri nci p al I n v esti g at or(s) 
 
 
 
 
 
C o nfi d e nti alit y St at e m e nt  
T h e i nf or m ati o n c o nt ai n e d i n t his d oc u m e nt is c o nfi d e nti al a n d t h e pr o pri et ary pr o p e rty of 
M e dtr o nic. A ny distri b uti o n, c o pyi n g, or discl os ur e wit h o ut t h e pri or writt e n a ut h oriz ati o n of 
M e dtr o nic is strictly pr o hi bi t e d. P ers o ns t o w h o m t h e i nf or m ati o n is discl os e d m ust k n o w t h at it is 
c o nfi d e nti al a n d t h at it m ay n ot b e f urt h er discl os e d by t h e m.  
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
T a bl e of  C o nt e nt s  
 
 
T a bl e of C o nt e nt s  
T a bl e  of  C o nt e nt s  ...................................................................................................................... 2  
1.  
Gl o s s ar y  .............................................................................................................................. 6  
2.  
S y n o p si s  ............................................................................................................................. 8  
3.  
I ntr o d u cti o n  ..................................................................................................................... 1 0  
3. 1.  B ac k gr o u n d  .......................................................................................................................... 1 0  
3. 2.  P ur p os e  ................................................................................................................................ 1 2  
4.  
O bj e cti v e s  a n d  E n d p oi nt s  ................................................................................................. 1 2  
4. 1.  O bj ecti v es  ............................................................................................................................. 1 2  
4. 1. 1.  
Pri m ar y  O bj ecti v e(s)  .............................................................................................................. 1 2  
4. 2.  Pri m ar y  E n d p oi nts  ................................................................................................................ 1 2  
4. 2. 1.  
Pri m ar y S af et y  E n d p oi nt  ........................................................................................................ 1 2  
4. 2. 2.  
Pri m ar y  Eff ectiv e n ess  E n d p oi nt  ............................................................................................ 1 2  
4. 3.  A d diti o n al O utc o m e  M e as ur es  .............................................................................................. 1 3  
4. 4.  R ati o n al e f or S el ecti o n of  St u d y E n d p oi nts  ............................................................................ 1 4  
5.  
St u d y D e si g n  .................................................................................................................... 1 5  
5. 1.  D ur ati o n  ............................................................................................................................... 1 5  
5. 2.  R ati o n al e  .............................................................................................................................. 1 6  
6.  
Pr o d u ct  D e s cri pti o n  .......................................................................................................... 1 6  
6. 1.  G e n er al  ................................................................................................................................. 1 6  
6. 2.  P ac k a gi n g  ............................................................................................................................. 1 6  
6. 3.  Pr o d uct  Tr ai ni n g  R e q uir e m e nts  ............................................................................................. 1 7  
6. 4.  Pr o d uc t Acc o u nt a bilit y  .......................................................................................................... 1 7  
6. 5.  Pr o d uct St or a g e  .................................................................................................................... 1 8  
6. 6.  Pr o d uct R et ur n  ..................................................................................................................... 1 8  
7.  
S el e cti o n of  S u bj e ct s  ........................................................................................................ 1 8  
7. 1.  St u d y P o p ul ati o n  .................................................................................................................. 1 8  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
7. 2.  S u bj ect  E nr oll m e nt  ................................................................................................................ 1 8  
7. 3.  I ncl usi o n Crit eri a  ................................................................................................................... 1 9  
7. 4.  E xcl usi o n  Crit eri a  .................................................................................................................. 1 9  
8.  
St u d y Pr o c e d ur e s  ............................................................................................................. 2 0  
8. 1.  Sc h e d ul e  of E v e nts  ................................................................................................................ 2 0  
8. 2.  S u bj ect  C o ns e nt  .................................................................................................................... 2 1  
8. 3.  S u bj ect  Scr e e ni n g  .................................................................................................................. 2 2  
8. 4.  H ar m o n y T P V 2 5  R oll -I n P h as e  ............................................................................................... 2 3  
8. 5.  A d diti o n of m T P V  2 5  C o h ort  .................................................................................................. 2 5  
8. 6.  I m pl a nt C at h eriz ati o n  Pr oc e d ur e  ........................................................................................... 2 6  
8. 6. 1.  
P ost -Pr oc e d ur e C ar e  ............................................................................................................. 2 7  
8. 6. 2.  
Disc h ar g e  Crit eri a  .................................................................................................................. 2 7  
8. 6. 3.  
D evic e  Ex pl a nt  ....................................................................................................................... 2 7  
8. 7.  S u bj ect  E v al u ati o ns  ............................................................................................................... 2 7  
8. 7. 1.  
U n pl a n n e d  Visits  ................................................................................................................... 2 7  
8. 7. 2.  
Miss e d  Visits  .......................................................................................................................... 2 8  
8. 8.  S u bst a nti al R a di ati o n  D os e  L e v el ........................................................................................... 2 8  
8. 9.  Ass ess m e nt  of  S af et y  ............................................................................................................ 2 8  
8. 1 0.  
R ec or di n g D at a  ................................................................................................................ 2 9  
8. 1 1.  
D e vi ati o n  H a n dli n g  .......................................................................................................... 2 9  
8. 1 2.  
S u bj ect Wit h dr a w al or Disc o nti n u ati o n  ............................................................................ 3 1  
9.  
Ri s k s  a n d  B e n efit s  ............................................................................................................ 3 1  
9. 1.  P ot e nti al Ris ks  ...................................................................................................................... 3 1  
9. 2.  P ot e nti al  B e n efi ts ................................................................................................................. 3 2  
9. 3.  Ris k -B e n efit  R ati o n al e  ........................................................................................................... 3 2  
1 0.  
A d v er s e E v e nt s  a n d  D e vi c e  D efi ci e n ci e s  ....................................................................... 3 3  
1 0. 1.  
D efi niti o ns/ Cl assific ati o ns  ............................................................................................... 3 3  
1 0. 2.  
E v al u ati o ns a n d D oc u m e nt ati o n of A d v ers e E v e nts a n d  D e vic e  D efici e nci es  ...................... 3 5  
1 0. 2. 1.  R e p orti n g of A dv ers e Ev e nts  b y I nv esti g at or  ........................................................................ 3 5  
1 0. 2. 2.  R e p orti n g of A dv ers e Ev e nts  by S p o ns or  .............................................................................. 3 7  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
1 0. 2. 3.  Cl assific ati o n of S eri o us  A dv ers e Ev e nts  ............................................................................... 3 8  
1 0. 2. 4.  Cl assific ati o n of  C a us al  R el ati o ns hi ps  ................................................................................... 3 8  
1 0. 2. 5.  R e p orti n g of  D e vic e  D efici e nci es  ........................................................................................... 3 9  
1 0. 3.  
A ntici p at e d  A d v ers e  E v e nts  ............................................................................................. 4 0  
1 0. 4.  
E m er g e nc y C o nt act D et ails f or R e p orti n g S A E, U A D E, a n d  D e vic e  D efici e nci es  ................... 4 0  
1 1.  
D at a  R e vi e w C o m mitt e e s  .............................................................................................. 4 0  
1 1. 1.  
Scr e e ni n g  C o m mitt e e  ...................................................................................................... 4 0  
1 1. 2.  
Cli nic al E v e nts  C o m mitt e e  ............................................................................................... 4 0  
1 1. 3.  
D at a  M o nit ori n g  C o m mitt e e  ............................................................................................ 4 1  
1 2.  
St ati sti c al D e s i g n a n d  M et h o d s  ..................................................................................... 4 2  
1 2. 1.  
A n al ysis  S ets  ................................................................................................................... 4 2  
1 2. 2.  
Pri m ar y  O bj ecti v es  .......................................................................................................... 4 2  
1 2. 2. 1.  Pri m ar y S af e t y E n d p oi nt  ........................................................................................................ 4 3  
1 2. 2. 2.  Pri m ar y  Effic ac y E n d p oi nt  ..................................................................................................... 4 3  
1 2. 3.  
A d diti o n al O utc o m e  M e as ur es  ........................................................................................ 4 4  
1 3.  
Et hi c s  ............................................................................................................................. 4 6  
1 3. 1.  
St at e m e nt(s)  of  C o m pli a nc e  ............................................................................................. 4 6  
1 3. 2.  
I nstit uti o n al R e vi e w B o ar d/ Et hics  C o m mitt e e  .................................................................. 4 7  
1 3. 3.  
R e g ul at or y S u b missi o ns  ................................................................................................... 4 8  
1 3. 4.  
Et hic al C o n d uct of  t h e St u d y  ............................................................................................ 4 8  
1 4.  
St u d y A d mi ni str ati o n  ..................................................................................................... 4 9  
1 4. 1.  
Sit e  Acti v ati o n  ................................................................................................................. 4 9  
1 4. 2.  
M o nit ori n g  ...................................................................................................................... 4 9  
1 4. 2. 1.  Pr e -St u dy  Visits ...................................................................................................................... 5 0  
1 4. 2. 2.  I nt eri m M o nit ori n g  ................................................................................................................ 5 0  
1 4. 2. 3.  St u dy Cl os e -O ut  ..................................................................................................................... 5 0  
1 4. 3.  
A u diti n g  .......................................................................................................................... 5 1  
1 4. 4.  
S o urc e  D at a/ D oc u m e nts  .................................................................................................. 5 1  
1 4. 5.  
C o nfi d e nti alit y  ................................................................................................................ 5 2  
1 4. 6.  
D at a  M a n a g e m e nt  .......................................................................................................... 5 2  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
1 4. 7.  
Li a bilit y ........................................................................................................................... 5 3  
1 4. 8.  
CI P  A m e n d m e nts  ............................................................................................................. 5 3  
1 4. 9.  
P u blic ati o n a n d Us e  of  I nf or m ati o n .................................................................................. 5 3  
1 4. 1 0.  
S us p e nsi o n or E arl y T er mi n ati o n of  t h e St u d y  ............................................................... 5 4  
1 4. 1 1.  
S us p e nsi o n or E arl y T er mi n ati o n of a  St u d y Sit e  ............................................................ 5 4  
1 5.  
R e c or d R et e nti o n a n d  R e p orti n g  R e s p o n si biliti e s  ......................................................... 5 4  
1 5. 1.  
R es p o nsi biliti es of  t h e I n v esti g at or .................................................................................. 5 4  
1 5. 2.  
R es p o nsi biliti es of  t h e S p o ns or  ........................................................................................ 5 7  
1 5. 3.  
R ec or d  R et e nti o n  ............................................................................................................ 6 2  
1 6.  
R ef er e n c e s  ..................................................................................................................... 6 2  
1 7.  
A p p e n di c e s  .................................................................................................................... 6 4  
1 8.  
V er si o n Hi st or y  .............................................................................................................. 6 5  
A p p e n di x I: I N F O R M E D  C O N S E N T T E M P L A T E  ......................................................................... 6 7  
A p p e n di x I I: A D V E R S E  E V E N T  D E F I N I T I O N S  ......................................................................... 6 8  
A p p e n di x I I I: A D V E R S E E V E N T C O D E  L I S T  ............................................................................. 7 3  
A p p e n di x I V:  E C H O C A R D I O G R A P H Y  P R O T O C O L  .................................................................... 7 7  
A p p e n di x V:  R A D I O G R A P H Y  P R O T O C O L  ................................................................................. 8 4  
A p p e n di x V I: C A R D I A C M A G N E T I C R E S O N A N C E I M A G I N G P R O T O C O L -F U N C T I O N A L  
P A R A M E T E R S  .......................................................................................................................... 8 6  
A p p e n di x V I I: C O M P U T E D T O M O G R A P H I C A N G I O G R A P H Y ( C T )  I M A G I N G  P R O T O C O L  ...... 1 0 3  
A p p e n di x V I I I: A N A T O M I C M E A S U R E M E N T S A N D D E V I C E  S I Z I N G  G U I D E L I N E S  ................ 1 0 8  
A p p e n di x I X:  E X P L A N T P R O T O C O L  ....................................................................................... 1 1 1  
A p p e n di x X: I N S T R U C T I O N S F O R  U S E  D O C U M E N T  .............................................................. 1 1 2  
A p p e n di x X I:  S F -3 6 Q U E S T I O N N A I R E ................................................................................... 1 1 3  
A p p e n di x X I I: P O S T -I M P L A N T C O M P U T E D T O M O G R A P H I C A N G I O G R A P H Y ( C T A ) I M A G I N G  
S U B -S T U D Y  P R O T O C O L  ......................................................................................................... 1 1 9  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
Titl e  
T h e M e dtr o nic H ar m o n y Tr a nsc at h et er P ul m o n ar y V al v e Cli nic al St u d y  
Pr o d uct N a m e  
H ar m o n y Tr a nsc at h et er P ul m o n ar y V al v e ( T P V) ( M o d el N T P V 0 0 2 2 ) 
H ar m o n y Tr a nsc at h et er P ul m o n ar y V al v e ( T P V) ( M o d el H T P V 2 5 4 9 5 2) 
H ar m o n y Tr a nsc at h et er P ul m o n ar y V al v e ( T P V) ( M o d el H T P V 2 5 4 2 5 2)  
 
H ar m o n y D eliv er y S yst e m ( D S) ( M o d el N T P V D S 0 0 2 2) 
H ar m o n y D eliv er y S yst e m ( D S) ( M o d el H T P V D S 0 0 2 5)  
S p o ns or  
M e dtr o nic  
C or o n ar y a n d  Str uct ur al H e art Cli nic al 
8 2 0 0 C or al S e a St N E, M V S 6 6 
M o u n ds Vi e w, M N 5 5 1 1 2  
U nit e d St at es  
L oc al S p o ns or(s) 
 
 
 
 
 
 
 
 
 
I n v esti g ati o n P ur p os e 
T h e p ur p os e of t his st u dy is t o e v al u at e t h e s af et y a n d eff ecti v e n ess of t h e 
H ar m o n y T P V s yst e m.  
Pri m ar y O bj ecti v e(s)  
T h e pri m ar y o bj ecti v e of t his st u d y is t o d e m o nstr at e t h e s af et y a n d 
eff ecti v e n ess of t h e H ar m o n y T P V s yst e m as m e as ur e d  b y fr e e d o m fr o m 
pr oc e d ur e or d evic e -r el at e d m ort alit y at 3 0 d a ys a n d p erc e nt a g e of s u bj ects 
wit h acc e pt a bl e h e m o d y n a mic f u ncti o n at 6 m o nt hs.  
Pri m ar y S af et y E n d p oi nt  
Fr e e d o m fr o m pr oc e d ur e - or d evic e -r el at e d m ort alit y at 3 0 d a ys. 
Pri m ar y Eff ecti v e n ess E n d p oi nt  
P erc e nt a g e of s u bj ects wit h acc e pt a bl e h e m o d y n a mic f u ncti o n c o m p osit e at 
6 m o nt hs as d efi n e d b y:  
•  
M e a n R V O T gr a di e nt as m e as ur e d b y c o nti n u o us -w a v e  D o p pl er 
ec h oc ar di o gr a p h y ≤4 0  m m H g  
o  
If a c at h et eriz ati o n is p erf or m e d f or cli nic al p ur p os es,  t h e 
c at het eriz ati o n p e a k gr a di e nt m e as ur e m e nt will s u p ers e d e t h e 
c o nti n u o us-w a v e D o p pl er ec h oc ar di o gr a p h y m e as ur e m e nt a n d 
b e us e d t o s u p p ort t h e pri m ar y e n d p oi nt. Acc e pt a bl e 
h e m o d y n a mic f u ncti o n as m e as ur e d b y c at h et eriz ati o n will b e 
c o nsi d er e d t o b e p e a k gr a d i e nt ≤4 0  m m H g.  
-A N D - 
•  
P ul m o n ar y r e g ur git a nt fr acti o n as m e as ur e d b y m a g n etic  r es o n a nc e 
i m a gi n g < 2 0 %  
2. S y n o p si s  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
o  
If m a g n etic r es o n a nc e i m a gi n g is c o ntr ai n dic at e d, a  c o nti n u o us- 
w a v e D o p pl er ec h oc ar di o gr a p h y m e as ur e m e nt will b e us e d t o 
s u p p ort t h e pri m ar y e n d p oi nt. Acce pt a bl e h e m o d y n a mic f u ncti o n 
as m e as ur e d b y c o nti n u o us -w a v e D o p pl er ec h oc ar di o gr a p h y will 
b e c o nsi d er e d t o b e < m o d er at e p ul m o n ar y  r e g ur git ati o n. 
A d diti o n al O utc o m e  M e as ur es  
•  
T ec h nic al  s ucc ess at  exit  fr o m c at h et eriz ati o n l a b/ o p er ati n g r o o m 
•  
D evic e s ucc ess o ut t o 5  y e ars  
•  
Pr oc e d ur al s ucc ess at 3 0  d a ys  
•  
Fr e e d o m fr o m T P V d ysf u ncti o n o ut t o 5  y e ars  
•  
Ass ess m e nt of  s af et y 
•  
C h ar act eriz e q u alit y of lif e sc or es o v er  ti m e 
•  
C h ar act eriz e ri g ht v e ntricl e r e m o d eli n g f oll o wi n g T P V  i m pl a nt 
•  
C o nfir m ati o n of t h e pr oc e d ur al f e asi bi lit y, h e m o d y n a mic p erf or m a nc e 
a n d s af et y pr ofil e of H ar m o n y T P V 2 5  (r oll -i n c o h ort) 
•  
C o nfir m ati o n of t h e pr oc e d ur al f e asi bilit y, h e m o d y n a mic  p erf or m a nc e 
a n d  s af et y pr ofil e of t h e m o difi e d T P V 2 5 ( 1 0 U S i m pl a nts) 
St u d y D esi g n  
M ulti -c e nt er, pr os p ecti v e, n o n -r a n d o miz e d, i nt er v e nti o n al, i n v esti g ati o n al 
I n v esti g ati v e Sit es 
U p t o 1 5 i n v esti g ati o n al sit es i n t h e U nit e d St at es, C a n a d a, a n d J a p a n  
S a m pl e Siz e  
•  
Pi v ot al c o h ort: Pri m ar y a n al ysis f or u p t o 4 0 s u bj ects i m pl a nt e d i ncl u di n g 
t h e H ar m o n y T P V 2 5 R oll-I n c o h ort 
•  
A d diti o n al  a n al ysis  f or t h e H ar m o n y  m o difi e d  T P V  2 5  ( m T P V 2 5)  c o h ort: 
t e n s u bj ects i m pl a nt e d i n t h e U nit e d St at es, a n d u p t o fi v e s u bj ects 
i m pl a nt e d i n C a n a d a a n d/ or J a p a n 
P ati e nt P o p ul ati o n  
P ati e nts w h o h a v e c o n g e nit al h e art dis e as e a n d ar e cli nic all y  i n dic at e d f or 
p ul m o n ar y v al v e r e pl ac e m e nt.  
I ncl usi o n Crit eri a 
•  
S u bj ect  h as  p ul m o n ar y  r e g ur git ati o n as  p er  o n e  or  m or e  of  t h e f oll o wi n g 
crit eri a: 
o  
S ev er e p ul m o n ar y r e g ur git ati o n as m e as ur e d b y c o nti n u o us -w a v e 
D o p pl er ec h oc ar di o gr a p h y,  or  
o  
P ul m o n ar y r e g ur git a nt fr acti o n ≥ 3 0 % as m e as ur e d b y  c ar di ac 
m a g n etic r es o n a nc e i m a gi n g  
•  
Cli nic al i n dic ati o n f or s ur gic al pl ac e m e nt of a R V -P A c o n d uit or 
pr ost h etic  p ul m o n ar y  v al v e  p er  o n e  or  m or e  of  t h e f oll o wi n g crit eri a: 
o  
S u bj ect is  s y m pt o m atic s ec o n d ar y t o p ul m o n ar y i ns uffi ci e nc y ( e. g. 
ex ercis e i nt ol er a nc e, fl ui d o v erl o a d) as cl assifi e d b y t h e 
i n v esti g at or, or  
o  
S u bj ect  h as  ri g ht v e ntric ul ar  e n d  di ast olic  v ol u m e  i n d ex ( R V E D Vi) 
≥ 1 5 0 ml/ m 2, or 
o  
S u bj ect h as R V E D V: L V E D V R ati o ≥ 2. 0  
•  
S u bj ect  is willi n g  t o c o ns e nt t o p artici p at e  i n t h e st u d y a n d  will  c o m mit 
t o c o m pl eti o n of all f oll o w-u p  r e q uir e m e nts 
E xcl usi o n Crit eri a  
•  
A n at o my u n a bl e t o acc o m m o d at e a 2 5 Fr d eli v er y  s yst e m 
•  
O bstr ucti o n of t h e c e ntr al  v ei ns  
•  
Cli nic al  or  bi ol o gic al  si g ns of  i nf ecti o n i ncl u di n g acti v e  e n d oc ar ditis  
•  
Pl a n n e d  c o nc o mit a nt pr oc e d ur e at ti m e of  i m pl a nt 
•  
P ositi v e pr e g n a nc y t est at b as eli n e ( pri or t o C T a n gi o gr a p h y a n d a g ai n 
pri or  t o i m pl a nt pr oc e d ur e)  i n f e m al e s u bj ects of  c hil d b e ari n g  p ot e nti al  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 of 1 2 1  
 
 
 
 
•  
P ati e nts wit h ri g ht v e ntric ul ar o utfl o w tr act o bstr ucti o n ( R V O T O)  l esi o ns 
s ur gic all y tr e at e d wit h a n R V-P A c o n d uit  i m pl a nt 
•  
A m aj or or pr o gr essi v e n o n -c ar di ac dis e as e ( e. g. li v er f ail ur e, r e n al 
f ail ur e, c a nc er) t h at r es ults i n a  lif e ex p ect a nc y  of  l ess t h a n o n e  y e ar  
•  
Pl a n n e d i m pl a nt ati o n of t h e H ar m o n y T P V i n t h e l eft  h e a rt 
•  
R V O T  a n at o my  or  m or p h ol o g y  t h at is u nf a v or a bl e  f or d evic e  a nc h ori n g  
•  
K n o w n all er g y t o as piri n, h e p ari n, or  nic k el  
•  
Ec h oc ar di o gr a p hic evi d e nc e of i ntr ac ar di ac m ass, t hr o m b us, or 
v e g et ati o n  
•  
Pr e -existi n g  pr ost h etic  h e art  v al v e  or  pr ost h etic  ri n g i n a n y  p osit i o n 
St u d y Pr oc e d ur es a n d 
Ass ess m e nts  
•  
Cli nic al ass ess m e nt at pr e - a n d p ost -i m pl a nt, 1 m o nt h, 6 m o nt hs, 1 y e ar, 
a n d a n n u all y t hr o u g h 5  y e ars  
•  
Ec h oc ar di o gr a p h y at pr e - a n d p ost -i m pl a nt, 1 m o nt h, 6 m o nt hs, 1 y e ar, 
a n d a n n u all y t hr o u g h 5  y e ars  
•  
C ar di ac m a g n etic r es o n a nc e ( C M R) at pr e-i m pl a nt, 6 m o nt hs, 2 y e ars, 
a n d 5  y e ars  
•  
C M R  at 1 m o nt h f or t h e m T P V 2 5  c o h ort 
•  
C T C ar di ac A n gi o gr a p h y at  pr e -i m pl a nt 
•  
C T C ar di ac A n gi o gr a p h y at p ost -i m pl a nt f or t h e m T P V 2 5 c o h ort a n d f or 
T P V 2 5 s u bj ects p artici p ati n g i n t h e C T  s u b-st u dy 
•  
Fl u or osc o p y at i m pl a nt, 1 m o nt h, 6 m o nt hs, 1 y e ar, a n d 5  y e ars  
•  
S F -3 6 at pr e -i m pl a nt, 1 m o nt h, 6 m o nt hs, 1 y e ar, a n d a n n u all y t hr o u g h 5 
y e ars  
Pr of essi o n al S er vic es  
•  
I n d e p e n d e nt Ec h oc ar di o gr a p h y C or e L a b or at or y 
•  
I n d e p e n d e nt C M R C or e L a b or at or y 
•  
I n d e p e n d e nt Ex pl a nt P at h ol o g y C or e  L a b or at or y 
•  
P ati e nt Scr e e ni n g  C o m mitt e e  
•  
I n d e p e n d e nt Cli nic al E v e nts C o m mitt e e  
•  
I n d e p e n d e nt D at a M o nit ori n g C o m mitt e e  
 
 
3. 1.  B a c k gr o u n d  
 
 
 
 
 
 
 
 
 
 
3. I ntr o d u cti o n  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 2  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 2.  P ur p o s e  
T h e p ur p os e of t his st u dy is t o e v al u at e t h e s af ety a n d eff ectiv e n ess of t h e H ar m o ny T P V s yst e m.  
 
 
4. 1.  O bj e cti v e s  
 
4. 1. 1.  
Pri m ar y  O bj e cti v e( s )  
T h e pri m ar y o bj ecti v e of t his st u dy is t o d e m o nstr at e t h e s af ety a n d eff ecti v e n ess of t h e H ar m o ny T P V 
s yst e m as m e as ur e d b y fr e e d o m fr o m pr oc e d ur e or d e vic e -r el at e d m ort alit y at 3 0 d a ys a n d p erc e nt a g e 
of s u bj ects wit h acc e pt a bl e h e m o dy n a mic f u ncti o n at 6 m o nt hs.  
 
4. 2.  Pri m ar y  E n d p oi nt s  
T h e f oll o wi n g e n d p oi nts will b e us e d t o e v al u at e t h e pri m ar y st u dy o bj ectiv e: 
 
4. 2. 1.  
Pri m ar y S af et y  E n d p oi nt  
➢ Fr e e d o m fr o m pr oc e d ur e - or d evic e -r el at e d m ort alit y at 3 0 d a ys  
 
4. 2. 2.  
Pri m ar y Eff e cti v e n e s s  E n d p oi nt  
➢ P erc e nt a g e of s u bj ects wit h acc e pt a bl e h e m o dy n a mic f u ncti o n c o m p osit e at 6 m o nt hs as 
d efi n e d  by:  
4. O bj e cti v e s a n d E n d p oi nt s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 3  of 1 2 1  
•  
M e a n R V O T gr a di e nt as m e as ur e d by c o nti n u o us -w av e D o p pl er ec h oc ar di o gr a p hy ≤4 0 
m m H g  
o  If a c at h et eriz ati o n is p erf or m e d f or cli nic al p ur p os es, t h e c at h et eriz ati o n p e a k 
gr a di e nt m e as ur e m e nt will s u p ers e d e t h e c o nti n u o us -w a v e D o p pl er 
ec h oc ar di o gr a p hy m e as ur e m e nt a n d b e us e d t o s u p p ort t h e pri m ary e n d p oi nt. 
Acc e pt a bl e h e m o dy n a mic f u ncti o n as m e as ur e d by c at h et eriz ati o n will b e c o nsi d er e d 
t o b e p e a k gr a di e nt ≤4 0 m m H g.  
-A N D - 
•  
P ul m o n ar y r e g ur git a nt fr acti o n as m e as ur e d by m a g n etic r es o n a nc e i m a gi n g  < 2 0 %  
o  If m a g n etic r es o n a nc e i m a gi n g is c o ntr ai n dic at e d, a c onti n u o us -w a v e D o p pl er 
ec h oc ar di o gr a p hy m e a s ur e m e nt will b e us e d t o s u p p ort t h e pri m ary e n d p oi nt. 
Acc e pt a bl e h e m o dy n a mic f u ncti o n as m e as ur e d by c o nti n u o us -w a v e D o p pl er 
ec h oc ar di o gr a p hy will b e c o nsi d er e d t o b e < m o d er at e p ul m o n ar y  r e g ur git ati o n. 
4. 3.  A d diti o n a l O ut c o m e M e a s ur e s  
➢ T ec h nic al s ucc ess at ex it fr o m c at h et eriz ati o n l a b/ o p er ati n g r o o m ( O R), as d efi n e d as:  
•  
N o d evic e - or pr oc e d ur al -r el at e d m ort ality, wit h  
•  
S ucc essf ul acc ess, d eli v er y a n d r etri ev al of t h e d eliv ery s yst e m,  a n d  
•  
D e pl oy m e nt a n d c orr ect p ositi o n i n g (i ncl u di n g mi n or r e p ositi o ni n g if n e e d e d) of t h e 
si n gl e i nt e n d e d d evic e, a n d  
•  
N o n e e d f or a d diti o n al u n pl a n n e d or e m er g e ncy s ur g er y or r e -i nt er v e nti o n r el at e d t o t h e 
d e vic e or acc ess  pr oc e d ur e  
➢ D evic e s ucc ess o ut t o 5 y e ars, as d efi n e d  as:  
•  
N o d evic e - or  pr oc e d ur al -r el at e d mort ality,  wit h  
•  
Ori gi n al i nt e n d e d d evic e i n pl ac e,  a n d  
•  
N o a d diti o n al s ur gic al or i nt er v e nti o n al pr oc e d ur es r el at e d t o acc ess or t h e d e vic e si nc e 
c o m pl eti o n of t h e ori gi n al pr oc e d ur e (i. e., exit fr o m t h e c at h et eriz ati o n l a b),  a n d  
•  
I nt e n d ed p erf or m a nc e of t h e d e vic e, as d efi n e d  as:  
o  Str uct ur al p erf or m a nc e: N o mi gr ati o n, e m b oliz ati o n, d et ac h m e nt, m aj or st e nt 
fr act ur e, h e m ol ysis, t hr o m b osis, e n d oc ar ditis, a n d  
o  H e m o dy n a mic p erf or m a nc e: R eli ef of i ns uffici e nc y ( P R < m o d er at e) wit h o ut 
pr o d uci n g t h e o p p osit e ( m e a n R V O T gr a di e nt > 4 0 m m H g) as m e as ur e d by 
c o nti n u o us-w a v e D o p pl er ec h oc ar di o gr a p hy 1, a n d  
•  
A bs e nc e of p ar a -d evic e c o m plic ati o ns, as d efi n e d  by:  
o  P VL ≥ m o d er at e,  or  
o  Er osi o n,  or  
1 If a c at h et eriz ati o n is p erf or m e d f or cli ni c al p ur p os es, t h e c at h et eriz ati o n p e a k gr a di e nt m e as ur e m e nt will s u p ers e d e t h e 
c o nti n u o us -w a v e D o p pl er e c h o c ar di o gr a p h y m e as ur e m e nt a n d b e u s e d t o s u p p ort t h e o ut c o m e m e as ur e.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 4  of 1 2 1  
 
 
 
o  R V O T or P A  r u pt ur e 
➢ Pr oc e d ur al s ucc ess at 3 0 d a ys, as d efi n e d  as:  
•  
D evic e s ucc ess at 3 0 d a ys,  a n d  
•  
N o n e of t h e f oll o wi n g d e vic e - or pr oc e d ur e -r el at e d s eri o us a d v ers e ev e nts:  
o  Lif e-t hr e at e ni n g m aj or bl e e d  
o  M aj or v asc ul ar or c ar di ac str uct ur al c o m plic ati o ns r e q ui r e d u n pl a n n e d 
r ei nt erv e nti o n or s ur g er y 
o  St a g e 2 or 3 ac ut e ki d n e y i nj ur y ( A KI) (i ncl u d es n e w  di al ysis)  
o  P ul m o n ar y  e m b olis m  
o  S e v er e h e art f ail ur e ( H F) or h y p ot e nsi o n r e q uiri n g I V i n otr o p e, ultr afiltr ati o n, or 
m ec h a nic al circ ul at ory  s u p p ort 
o  Pr ol o n g e d i nt u b ati o n > 4 8  h o urs  
➢ Fr e e d o m fr o m T P V dysf u ncti o n o ut t o 5 y e ars.  
 
➢ Ass ess m e nt of s af ety, d efi n e d as ass ess m e nt  of:  
•  
All pr oc e d ur e -r el at e d s eri o us a d v ers e e v e nts  
•  
All d e vic e -r el at e d s eri o us a dv ers e e v e nts  
•  
D e at h ( all -c a us e, pr oc e d ur al, a n d d e vic e -r el at e d) 
•  
C h ar act eriz a ti o n of q u alit y of lif e sc or es ov er ti m e as ass ess e d by t h e S F -3 6 at pr e - 
i m pl a nt, 1 m o nt h p ost-i m pl a nt, 6 m o nt hs p ost-i m pl a nt, a n d a n n u ally p ost-i m pl a nt o ut t o 
5  y e ars 
•  
C h ar act eriz ati o n  of ri g ht v e ntricl e r e m o d eli n g f oll o wi n g T P V i m pl a nt as ass ess e d vi a  C M R  
 
4. 4.  R ati o n al e f or S el e cti o n of St u d y  E n d p oi nt s  
T h e b asis f or t h e s el ecti o n of t h es e e n d p oi nts i ncl u d es t h e f oll o wi n g c o nsi d er ati o ns:  
 
•  
T h e y ar e cli nic ally r el e v a nt a n d a d dr ess i m p ort a nt s af et y a n d eff ectiv e n ess as p ects of t h e 
M e dtr o nic H ar m o ny T P V  s yst e m. 
•  
T h e y ar e o bj ecti v el y d efi n e d a n d m e as ur a bl e i n t h e m aj ority of  s u bj ects. 
•  
T h e y ar e c o nsist e nt wit h c urr e nt e n d p oi nts i n T P V cli nic al  st u di es. 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 5  of 1 2 1  
 
 
 
 
 
T his is a pr os p ecti v e, n o n -r a n d o miz e d, m ulti-c e nt er st u dy. U p t o 4 0 s u bj ects will b e i m pl a nt e d at a t ot al 
u p t o 1 5 c e nt ers i n t h e U nit e d St at es, C a n a d a, a n d J a p a n. It is a ntici p at e d t h at m or e t h a n 4 0 s u bj ects will 
b e e n r oll e d (i. e. c o ns e nt e d) t o m e et t h e t ar g et of u p t o 4 0 i m pl a nts as n ot all s u bj ects will b e 
a n at o mic all y s uit a bl e f or i m pl a nt ati o n. N o sit e s h all i m pl a nt m or e t h a n 1 0 s u bj ects i n t h e pi v ot al c o h ort 
t o av oi d bi as of t h e st u dy r es ults. S u bj ects w h o disc o nti nu e p artici p ati o n pr e m at ur el y f oll o wi n g i m pl a nt 
will b e i ncl u d e d i n t h e a n alysis of r es ults ( as a p pr o pri at e) a n d will n ot b e r e pl ac e d i n t h e e nr oll m e nt of 
t ot al st u dy s u bj ects i m pl a nt e d. All i m pl a nt e d s u bj ects will r ec ei v e t h e H ar m o ny T P V. E ac h i m pl a nt e d 
s ubj ect will b e f oll o w e d f or fi v e y e ars or u ntil t h e s u bj ect's H ar m o ny T P V is ex pl a nt e d.  
 
T h e a d diti o n of t h e s ec o n d d e vic e siz e ( H ar m o ny T P V 2 5) is i nt e n d e d t o ex p a n d t h e n u m b er of p ati e nts 
a n at o mic all y s uit a bl e f or i m pl a nt ati o n a n d will i ncl u d e a R oll -I n co h ort of H ar m o ny T P V 2 5 s u bj ects. T h e 
R oll -I n p h as e is d escri b e d i n S ecti o n 8. 4.  H ar m o n y T P V 2 5 R oll -I n P h as e. T h e a d diti o n of t h e l ar g er siz e d 
v al v e c o m pl et e d t h e piv ot al c o h ort of 4 0.  
 
F oll o wi n g t h e c o m pl eti o n of t h e 4 0 piv ot al c o h ort of t h e T P V 2 2 a n d T P V 2 5, t h e T P V 2 5 w as m o difi e d 
a n d is r ef err e d t o as m o difi e d T P V 2 5 ( m T P V 2 5). T h er e will b e a n a d d e d c o h ort of u p t o 1 5 s u bj ects 
i m pl a nt e d wit h t h e m T P V 2 5. T his a d diti o n al c o h ort will i ncl u d e 1 0 U S i m pl a nts a n d u p t o 5 O U S 
i m pl a nts fr o m C a n a d a a n d/ or J a p a n. T h e m T P V 2 5 c o h ort is d escri b e d i n S ecti o n 8. 5. A d diti o n of m T P V 
2 5 C o h ort . T h e st u dy m et h o ds i ncl u d e t h e f oll o wi n g m e as ur es t o mi ni miz e p ot e nti al s o urc es of bi as:  
 
•  
A Scr e e ni n g C o m mitt e e c o m pris e d of a s u bs et of st u dy i n v esti g at ors will c o nfir m s u bj ect 
eli gi bilit y a n d a n at o mic  s uit a bilit y 
•  
A n ext er n al, i n d e p e n d e nt Cli nic al E v e nts C o m mitt e e ( C E C) will r e vi e w a n d a dj u dic at e, at 
mi ni m u m, all d e at hs a n d e n d p oi nt r el at e d a d v ers e ev e nts. S af ety e n d p oi nt r es ults will b e b as e d 
o n C E C  a dj u dic ati o ns.  
•  
All  sit es will  f oll o w a  st a n d ar diz e d pr ot oc ol  f or ac q uisiti o n  of  ec h oc ar di o gr a p hic  e n d p oi nt  d at a.  
•  
A n Ec h o C or e L a b will ev al u at e all  ec h oc ar di o gr a ms.  
•  
A C M R C or e L a b will e v al u at e all f u ncti o n al C M R  r es ults. 
•  
St u dy e n d p oi nts, w h e n a p pr o pri at e, will b e b as e d o n C E C or C or e L a b  ass ess m e nts.  
•  
St u dy sit es will f oll o w t h eir i nstit uti o n al pr oc e d ur es f or m ai nt e n a nc e of ec h oc ar di o gr a p hy a n d 
i m a gi n g e q ui p m e nt us e d f or ass essi n g t h e st u dy v ari a bl es.  
 
5. 1.  D ur ati o n  
S u bj ects will b e c o ns e nt e d f or p ar tici p ati o n i n t h e st u dy f or f oll o w-u p t hr o u g h 5 y e ars. T h e e nr oll m e nt 
p eri o d f or t his st u dy is esti m at e d t o b e b et w e e n 1 8 t o 2 4 m o nt hs; t h er ef or e, t h e esti m at e d t ot al 
d ur ati o n of t h e st u dy (first s u bj ect e nr oll e d t o l ast s u bj ect c o m pl eti n g t h e l ast f oll o w -u p ex a m) is 
esti m at e d t o b e 7 y e ars.  
5. St u d y D e si g n  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 6  of 1 2 1  
 
 
 
W h e n t h e H ar m o ny T P V s yst e m r ec ei v es m ark eti n g a p pr o v al d uri n g t h e c o urs e of t his cli nic al tri al, t h e 
f oll o w-u p ass ess m e nts will c o nti n u e u ntil all s u bj ects h a v e c o m pl et e d 5 y e ars of f oll o w -u p.  
 
5. 2.  R ati o n al e  
T h e cli nic al st u dy d esi g n f or t his st u dy ali g ns wit h ot h er T P V st u di es, i ncl u di n g t h e M e dtr o nic N ativ e 
O utfl o w Tr act Tr a nsc at h et er P ul m o n ary V alv e R es e arc h Cli nic al St u dy. R es ults fr o m t h e M e dtr o nic 
N ati v e O utfl o w Tr act Tr a nsc at h et er P ul m o n ar y V al v e R es e a rc h Cli nic al St u dy s u p p ort j ustific ati o n of 
f urt h er i nv esti g ati o n of t his d e vic e i n h u m a ns a n d d e m o nstr at e t h es e e v al u ati o ns of cli nic al d at a ar e 
r el e v a nt t o t h e pr o p os e d i n v esti g ati o n. 
 
 
6. 1.  G e n er al  
T h e H ar m o ny T P V ( M o d el N T P V 0 0 2 2) is c o m pris e d of a 2 2 m m p orci n e p eric ar di u m v al v e, s e w n t o a 
p ol y est er -c ov er e d as y m m etric al h o ur gl ass niti n ol fr a m e. T h e H ar m o ny T P V 2 5 a n d m T P V 2 5 ( M o d el 
H T P V 2 5 4 9 5 2 a n d H T P V 2 5 4 2 5 2, r es p ectiv ely) is c o m pris e d of a 2 5 m m p orci n e p eric ar di u m v al v e, s e w n t o 
a p ol y est er c o v er e d asy m m etric al h o ur gl ass niti n ol fr a m e wit h l ar g er di a m et er i nfl o w a n d o utfl o w as 
w ell as s h ort er l e n gt h c o m p ar e d t o T P V 2 2. All T P V siz es ar e pr oc ess e d w it h a n a nti-mi n er aliz ati o n 
tr e at m e nt of al p h a-a mi n o ol eic aci d ( A O A ®), a c o m p o u n d d eri v e d fr o m ol eic aci d, a n at ur ally occ urri n g 
l o n g-c h ai n f atty aci d. T h e H ar m o ny D eliv ery S yst e m ( D S) f or t h e T P V 2 2, T P V 2 5, a n d m T P V 2 5 
( N T P V D S 0 0 2 2 a n d H T P V D S 0 0 2 5) ar e all 2 5 Fr d eliv ery s yst e ms usi n g a c oil l o a di n g c at h et er. R ef er t o t h e 
H ar m o ny T P V a n d D S I nstr ucti o ns f or Us e (I F U) d oc u m e nts f or e ac h d e vic e f or f ull i nf or m ati o n r e g ar di n g 
t h e pr o d uct, w hic h i ncl u d es a d escri pti o n of t h e pr o d ucts b ei n g i n v esti g at e d, m a n uf act ur er i nf or m ati o n, 
p ac k a gi n g i nf or m ati o n, i nt e n d e d p o p ul ati o n d escri pti o n, a n d i nstr ucti o ns f or pr o d uct  us e.  
 
6. 2.  P a c k a gi n g  
L a b eli n g of t h e H ar m o ny T P V syst e m will b e pr ovi d e d i n E n glis h a n d t h e l oc al l a n g u a g e, if n e e d e d 
acc or di n g t o l oc al r e q uir e m e nts. T h e l a b eli n g will i n dic at e t h at t h e d e vic e is f or i n v esti g ati o n al us e o nl y, 
a n d o nl y t o b e us e d by q u alifi e d i n v esti g at ors, a n d c o nsist e nt wit h t h e r e q uir e m e nts of t h e g e o gr a p hi es 
w h er e t h e tri al is c o n d uct e d.  
 
T h e I F U f or t h e H ar m o ny T P V s yst e m us e d i n t his tri al will b e pr ovi d e d as a s e p ar at e d oc u m e nt. If 
c h a n g es ar e m a d e t o t h e l a b eli n g, t h e y will b e pr ovi d e d u n d er s e p ar at e c ov er t o t h e a p pr o pri at e 
a ut h oriti es p er l oc al r e q uir e m e nts.  
6. Pr o d u ct D e s cri pti o n  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 7  of 1 2 1  
6. 3.  Pr o d u ct Tr ai ni n g  R e q uir e m e nt s  
Pri or t o first p ati e nt i m pl a nt at a n i nv esti g ati v e sit e, M e dtr o nic will pr o vi d e pr o d uct tr ai ni n g t o t h e 
i m pl a nti n g p hysici a n(s). I m pl a nti n g p hysici a ns will r ec ei v e di d actic pr o d uct tr ai ni n g a n d h a n ds-o n d e vic e 
tr ai ni n g. At a mi ni m u m, t h e first c as e at e ac h i nv esti g ati v e sit e f or e ac h v alv e siz e will b e s u p p ort e d b y 
a n ex p eri e nc e d H ar m o ny T P V i m pl a nt er. A d dit i o n al i m pl a nt s u p p ort m a y b e pr ovi d e d as n e e d e d. 
6. 4.  Pr o d u ct  A c c o u nt a bilit y  
T h e H ar m o ny T P V a n d D S ar e n ot a p pr ov e d f or us e i n a ny g e o gr a p hy, a n d t h er ef or e ar e c o nsi d er e d 
i nv esti g ati o n al d evic es. T h e i nv esti g at or s h all m ai nt ai n a d e q u at e r ec or ds of t h e r ec ei pt a n d dis p ositi o n 
of all i nv esti g ati o n al d e vic es.  
C e nt ers ar e r e q uir e d t o m ai nt ai n i n v esti g ati o n al d e vic e r ec or ds t h at c o nt ai n t h e f oll o wi n g i nf or m ati o n:  
•  
I nv esti g ati o n al d evic e n a m e  
•  
D evic e s eri al n u m b er ( w h e n  a p plic a bl e)  
•  
L ot n u m b er ( w h e n a p plic a bl e)  
•  
Us e by  d at e  
•  
D at e of r ec ei pt of  d evic e  
•  
N a m e of p ers o n r ec ei vi n g t h e  d e vic e  
•  
N a m e of p ers o n usi n g t h e d e vic e ( w h e n  a p plic a bl e)  
•  
D at e of us e ( w h e n  a p plic a bl e)  
•  
I D n u m b er of s u bj ect r ec eivi n g t h e d e vic e ( w h e n a p plic a bl e)  
•  
Dis p ositi o n ( u n us e d, dis p os e d of, i m pl a nt e d, or r et ur n e d t o M e dtr o nic)  
F or d evic es t h at ar e r et ur n e d t o M e dtr o nic or dis p os e d of, c e nt ers ar e r e q uir e d t o d oc u m e nt t h e 
f oll o wi n g a d diti o n al i nf or m ati o n: 
•  
T h e q u a ntit y a n d r e as o n f or t h e d evic e b ei n g r et ur n e d t o M e dtr o nic or dis p os e d  of  
•  
N a m e of t h e p ers o n w h o dis p os e d of e ac h  d evic e  
•  
D at e of s hi p m e nt b ac k t o  M e dtr o nic  
At t h e c o m pl eti o n of t h e st u dy i m pl a nt p eri o d, t h e i nv esti g at or m ust r et ur n all u n us e d d e vic es a n d a 
c o py of t h e c o m pl et e d d evic e i nv e nt or y t o M e dtr o nic. T h e i nv esti g at or’s c o py of t h e d e vic e 
r ec o ncili ati o n r ec or ds m ust d oc u m e nt a ny u n us e d d evic es t h at h a v e b e e n r et ur n e d t o M e dtr o nic as w ell 
as all pr o d uct us a g e i ncl u di n g o p e n e d b ut n o n -i m pl a nt e d d evic es. 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 8  of 1 2 1  
 
 
 
6. 5.  Pr o d u ct  St or a g e  
T h e H ar m o ny T P V a n d D S ar e n ot a p pr ov e d f or us e i n a ny g e o gr a p hy, a n d t h er ef or e ar e c o nsi d er e d 
i nv esti g ati o n al d evic es. As s uc h, t h e y s h o ul d b e st or e d as l a b el e d a n d i n a s ec ur e/l oc k e d st or a g e ar e a 
wit h acc ess li mit e d o nly t o a p pr o v e d st u dy st aff. T h e m et h o d of st or a g e s h o ul d pr e v e nt t he us e of t h es e 
i nv esti g ati o n al d evic es f or a p plic ati o ns ot h er t h a n d escri b e d i n t his Cli nic al I nv esti g ati o n Pl a n ( CI P). T h e 
i nv esti g at or s h all m ai nt ai n a d e q u at e r ec or ds of t h e r ec ei pt a n d dis p ositi o n of all i nv esti g ati o n al d evic es. 
 
6. 6.  Pr o d u c t R et ur n  
I n t h e ev e nt of a d e vic e m alf u ncti o n of t h e H ar m o ny T P V syst e m pri or t o i m pl a nt, or i n t h e ev e nt t h e 
H ar m o ny T P V is ex pl a nt e d aft er i m pl a nt ( d u e t o r ei nt er v e nti o n or a ut o psy), t h e H ar m o ny T P V a n d/ or 
aff ect e d c o m p o n e nts s h o ul d b e s e nt t o M e dtr o nic.  
 
A d diti o n al d et a ils s urr o u n di n g t h e d evic e r et ur n pr oc ess ar e c o nt ai n e d wit hi n t h e M e dtr o nic ex pl a nt kit 
t h at will b e pr ovi d e d u p o n n otific ati o n of a d e vic e m alf u ncti o n or ex pl a nt. T o o bt ai n a pr o d uct r et ur n kit, 
c o nt act a M e dtr o nic R e pr es e nt ativ e. If a k it is n ot av ail a bl e, pl ac e t h e ex pl a nt e d v al v e i n a c o nt ai n er of 
gl ut ar al d e h y d e or 1 0 % b uff er e d f or m ali n i m m e di at el y aft er excisi o n.  
 
S p ecific p at h ol o gic al st u di es of a n ex pl a nt e d v alv e will b e c o n d uct e d u n d er t h e dir ecti o n of a c o ns ulti n g 
p at h ol o gist. A w ritt e n s u m m ar y of t h e fi n di n gs will b e r et ur n e d t o t h e p hysici a n. F or s p ecific i nstr ucti o ns 
r e g ar di n g ex pl a nt, r ef er t o A p p e n di x I X: E X PL A N T P R O T O C OL . 
 
 
7. 1.  St u d y  P o p ul ati o n  
T h e p o p ul ati o n i ncl u d es p ati e nts w h o h av e c o n g e nit al h e art dis e as e a n d ar e cli nic all y i n dic at e d f or 
p ul m o n ary v alv e r e pl ac e m e nt.  
 
7. 2.  S u bj e ct  E nr oll m e nt  
T h e pr oc ess of s u bj ect e nr oll m e nt is as f oll o ws:  
7. S el e cti o n of S u bj e ct s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 9  of 1 2 1  
 
 
 
1.  P ati e nts i d e ntifi e d b y or pr es e nt e d t o t h e st u dy sit e w h o h a v e c o n g e nit al h e art dis e as e a n d ar e 
cli nic all y i ndic at e d f or p ul m o n ar y v alv e r e pl ac e m e nt will b e scr e e n e d by t h e i n v esti g at or or 
d esi g n e e f or t h e crit eri a d escri b e d i n S ecti o n 7. 3 . I ncl usi o n Crit eri a a n d S ecti o n 7. 4 . E xcl usi o n 
Crit eri a , usi n g av ail a bl e m e dic al r ec or ds, i ncl u di n g r el ev a nt i m a gi n g st u di es pr e vi o usl y 
p erf or m e d f or di a g n ostic  p ur p os es.  
2.  If t h e p ati e nt is d e e m e d a p ot e nti al c an di d at e f or t h e st u dy, t h e i nv esti g ati o n al st at us of t h e 
H ar m o ny T P V a n d all as p ects of t h e st u dy will b e ex p l ai n e d t o t h e p ati e nt. T h e p ati e nt will t h e n 
b e i nvit e d t o p artici p at e i n t h e  st u dy. 
3.  If t h e p ati e nt a gr e es t o p artici p at e, writt e n i nf or m e d c o ns e nt will b e o bt ai n e d. T his will b e 
c o nsi d er e d t h e p oi nt of e nr oll m e nt, a n d t h e s u bj ect will b e assi g n e d a s u bj ec t I D n u m b er.  
 
7. 3.  I n cl u si o n  Crit eri a  
•  
S u bj ect h as p ul m o n ary r e g ur git ati o n as p er o n e or m or e of t h e f oll o wi n g  crit eri a: 
o  S e v er e p ul m o n ar y r e g ur git ati o n as m e as ur e d by c o nti n u o us-w a v e D o p pl er 
ec h oc ar di o gr a p hy,  or  
o  P ul m o n ar y r e g ur git a nt fr acti o n ≥ 3 0 % as m e as ur e d b y c ar di ac m a g n etic r es o n a nc e 
i m a gi n g 
•  
Cli nic al i n dic ati o n f or s ur gic al pl ac e m e nt of a R V -P A c o n d uit or pr ost h etic p ul m o n ar y v al v e p er  
o n e or m or e of t h e f oll o wi n g  crit eri a: 
o  S u bj ect is sy m pt o m atic s ec o n d ar y t o p ul m o n ar y i ns uffici e nc y ( e. g. ex ercis e i nt ol er a nc e, 
fl ui d o v erl o a d) as cl assifi e d b y t h e i n v esti g at or, or  
o  S u bj ect h as ri g ht v e ntric ul ar e n d di ast olic v ol u m e i n d ex ( R V E D Vi) ≥ 1 5 0 ml / m2, or  
o  S u bj ect h as R V E D V: L V E D V R ati o ≥ 2. 0  
•  
S u bj ect is willi n g t o c o ns e nt  t o p artici p at e i n t h e st u dy a n d will c o m mit t o c o m pl eti o n of all 
f oll o w-u p  r e q uir e m e nts 
 
7. 4.  E x cl u si o n  Crit eri a  
•  
A n at o m y u n a bl e t o acc o m m o d at e a 2 5 Fr d eliv ery  syst e m 
•  
O bstr ucti o n of t h e c e ntr al  v ei ns 
•  
Cli nic al or bi ol o gic al si g ns of i nf ecti o n i ncl u di n g activ e  e n d oc ar ditis  
•  
Pl a n n e d c o nc o mit a nt pr oc e d ur e at ti m e of H ar m o ny T P V  i m pl a nt 
•  
P ositi v e pr e g n a ncy t est at b as eli n e ( pri or t o C T a n gi o gr a p hy a n d a g ai n pri or t o i m pl a nt 
pr oc e d ur e) i n f e m al e s u bj ects of c hil d b e ari n g  p ot e nti al  
•  
P ati e nts wit h ri g ht v e ntric ul ar o utfl o w tr act o bstr ucti o n ( R V O T O) l esi o ns s ur gic ally tr e at e d wit h 
a R V - P A c o n d uit  i m pl a nt 
•  
A m aj or or pr o gr essiv e n o n -c ar di ac dis e as e ( e. g. liv er f ail ur e, r e n al f ail ur e,  c a nc er) t h at r es ults i n 
a lif e ex p ect a nc y of l ess t h a n o n e  y e ar 
•  
Pl a n n e d i m pl a nt ati o n of t h e H ar m o ny T P V i n t h e l eft  h e art  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 1  of 1 2 1  
 
 
 
 
5 If a C M R f u ncti o n al ex a m h as b e e n p erf or m e d f or r o uti n e di a g n ostic p ur p os es pri or t o c o ns e nti n g, it c a n b e us e d as t h e pr e- 
i m pl a nt C M R f u ncti o n al ex a m, pr o vi d e d it w as p erf or m e d wit hi n 5 2 w e eks pri or t o i m pl a nt. T h e Pri nci p al I nv esti g at or m ust 
d et er mi n e if t h e ex a m c o nt ai ns t h e pr ot oc ol -r e q uir e d d at a a n d r e m ai ns a d e q u at e f or s u bj ect ev al u ati o n. 
6 F u ncti o n al C M R at t h e 1 m o nt h visit will b e r e q uir e d f or s u bj ects i m pl a nt e d wit h m T P V 2 5.  
7 C T p ost i m pl a nt wi ll b e r e q uir e d f or s u bj ects i m pl a nt e d wit h T P V 2 5 w h o ar e p artici p ati n g i n t h e P ost I m pl a nt C T s u b-st u dy 
f ollo wi n g A p p e n di x XII . 
8 If a C T c ar di ac a n gi o gr a p hy ex a m h as pr evi o usl y b e e n p erf or m e d pri or t o c o ns e nti n g, it c a n b e us e d as t h e pr e -i m pl a nt C T ex a m, 
pr o vi d e d it w as p erf or m e d wit hi n 2 y e ars pri or t o i m pl a nt. T h e Pri nci p al I n v esti g at or m ust d et er mi n e if t h e ex a m c o nt ai ns t h e 
pr ot oc ol -r e q uir e d d at a a n d r e m ai ns a d e q u at e f or s u bj ect ev al u ati o n ( e. g. s u bj ect h as n ot u n d er g on e si g nific a nt gr o wt h i n t h e 
i nt eri m). Pr e-i m pl a nt C T a n gi o gr a p hy will f oll o w A p p e n dix VII. 
9 C T at disc h ar g e  will b e r e q uir e d f or s u bj ects i m pl a nt e d wit h t h e m T P V 2 5 w h o ar e p artici p ati n g i n t h e P ost I m pl a nt C T s u b -st u dy 
f oll o wi n g A p p e n di x XII . 
1 0 S F -3 6 is s uit a bl e f or s elf -a d mi nistr ati o n or a d mi nistr ati o n by a n i nt er vi e w er i n p er s o n or by t el e p h o n e. 
1 1 T h e pr e -i m pl a nt S F-3 6 c a n b e a d mi nist er e d aft er a s u bj ect h as b e e n ev al u at e d by t h e scr e e ni n g c o m mitt e e b ut pri or t o i m pl a nt. 
1 2 I nv esti g at ors ar e r e q uir e d t o ev al u at e a n d d oc u m e nt i n t h e s u bj ect’s m e dic al r ec or ds all a dv ers e ev e nts  a n d d evic e d efici e nci es 
o bs er v e d i n st u dy s u bj ects fr o m t h e ti m e t h ey ar e e nr oll e d (c o ns e nt e d) u ntil t h ey ar e exit e d fr o m t h e st u dy.  
 
8. 2.  S u bj e ct  C o n s e nt  
Pri or t o e nr olli n g i n t h e st u dy, p ati e nts s h o ul d b e f ull y i nf or m e d of t h e d et ails of st u dy  p artici p ati o n as 
r e q uir e d b y a p plic a bl e r e g ul ati o ns, t h e sit e’s I R B/ E C a n d b y M e dtr o nic. I nf or m e d c o ns e nt m ust b e 
o bt ai n e d fr o m e ac h p ati e nt or l e g all y a ut h oriz e d r e pr es e nt ativ e pri or t o c o n d ucti n g a n y pr ot oc ol - 
i n d uc e d acti viti es b e y o n d st a n d ar d of c ar e, by usi n g t h e i nf or m e d c o ns e nt f or m (I C F) a p pr ov e d b y t h at 
sit e’s I R B/ E C a n d b y M e dtr o nic. T h e I C F m ust b e si g n e d a n d d at e d b y t h e p ati e nt or l e g al r e pr es e nt ativ e. 
A ny a d diti o n al p ers o ns r e q uir e d b y t h e sit e’s I R B/ E C t o si g n t h e i nf or m e d c o ns e nt f or m m ust als o 
c o m pl y. I n J a p a n, t h e r el ati o ns hi p b et w e e n t h e p ati e nt a n d l e g al r e pr es e nt ati v e m ust b e d oc u m e nt e d i n 
t h e I C F a n d I C pr oc ess if a l e g al r e pr es e nt ativ e si g n e d t h e I C F. 
 
T his st u dy h as t h e p ot e nti al t o i ncl u d e i n di vi d u als t h at m ay b e c o nsi d er e d v ul n er a b l e. T h e I nv estig at or 
s h o ul d c o nsi d er t h e d efi niti o n of v ul n er a bl e p er I S O 1 4 1 5 5, w hic h d efi n es v ul n er a bl e p ati e nts as: “t h os e 
p ati e nts t h at c o ul d b e u n d ul y i nfl u e nc e d b y t h e ex p ect ati o n or b e n efits ass oci at e d wit h p artici p ati o n or 
of r et ali at or y r es p o ns e f r o m s e ni or m e m bers of a hi er arc h y i n c as e of r ef us al t o p artici p at e. F or 
ex a m pl e, t his c o ul d i ncl u d e I n di vi d u als wit h l oss of a ut o n o m y d u e t o i m m at urity or t hr o u g h m e nt al 
dis a bilit y, p ers o ns i n n ursi n g h o m es, c hil dr e n, i m p ov eris h e d p ers o ns, s u bj ects i n e m e r g e nc y sit u ati ons, 
et h nic mi n ority gr o u ps, h o m el ess p ers o ns, n o m a ds, r ef u g e es, a n d t h os e i nc a p a bl e of givi n g i nf or m e d 
c o ns e nt. Ot h er v ul n er a bl e s u bj ects c o ul d i ncl u d e, f or ex a m pl e, m e m b ers of a gr o u p wit h a hi er arc hic al 
str uct ur e s uc h as u ni v ersity st u d e nts, s u b or di n at e h os pit al a n d l a b or at ory p ers o n n el, e m pl oy e es of t h e 
s p o ns or, m e m b ers of t h e ar m e d f orc es, a n d p ers o ns k e pt i n d et e nti o n.” A ny a d diti o n al r e q uir e m e nts by 
t h e sit e’s I R B/ E C or l oc al r e g ul ati o ns r e g ar di n g t h e i nf or m e d c o ns e nt pr oc ess r e q uir e m e nts r el ati n g t o 
v ul n er a bl e p o p ul ati o ns m ust b e f oll o w e d.  
 
I nf or m e d ass e nt s h o ul d b e c o nsi d er e d d e p e n di n g o n t h e a g e a n d u n d erst a n di n g of t h e s u bj ect p er 
I R B/ E C r e q uir e m e nt a n d l oc al r e g ul ati o ns or w h e n t h e i n v esti g at or f e els t h at a mi n or c a n n ot u n d erst a n d 
th e c o nt e nt of t h e I C F s uffici e ntl y b ef or e a mi n or will b e e nr oll e d i n t h e st u dy. W h e n r e q uir e d, i nf or m e d 
ass e nt m ust b e o bt ai n e d usi n g t h e I R B/ E C a p pr o v e d f or m.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 2  of 1 2 1  
Pri or t o t h e p ati e nt or l e g al r e pr es e nt ativ e si g ni n g t h e I C F, t h e i nv esti g at or or a ut h oriz e d d esi g n e e will 
fully ex pl ai n t o t h e p ati e nt or l e g al r e pr es e nt ativ e t h e n at ur e of t h e r es e arc h, st u dy  pr oc e d ur es, 
a ntici p at e d b e n efits, a n d p ot e nti al ris ks of p artici p ati o n i n t h e st u dy. T h e i n v esti g at or or d esi g n e e will 
all o w a d e q u at e ti m e f or t h e p ati e nt or l e g al r e pr es e nt ati v e t o r e a d t h e c o ns e nt f or m a n d t o ask 
q u esti o ns. Si g ni n g t h e I C F s er v es t o d oc u m e nt t h e writt e n a n d v er b al i nf or m ati o n t h at t h e i n v esti g at or 
or d esi g n e e pr o vi d e d t o t h e p ati e nt or l e g al r e pr es e nt ati v e, t h e p ati e nt or l e g al r e pr es e nt ati v e’s 
u n d erst a n di n g of t h e i nf or m ati o n, a n d t h eir a gr e e m e nt t o p artici p at e. T h e c as e hist or y f or e ac h p ati e nt 
s h all d oc u m e nt t h e e ntir e i nf or m e d c o ns e nt pr oc ess i ncl u di n g w h o p artici p at e d i n t h e c o ns e nt 
disc ussi o ns a n d t h at i nf or m e d c o ns e nt w as o bt ai n e d pri or t o p artici p ati o n i n t h e st u dy. T h e ori gi n al 
si g n e d c o ns e nt f or m will b e r et ai n e d i n t h e p ati e nt’s st u dy r ec or ds a n d a c o py of t h e i nf or m e d c o ns e nt 
will b e pr o vi d e d t o t h e p ati e nt or l e g al r e pr es e nt ativ e.  
T h e p oi nt at w hic h t h e I C F ( a n d i nf or m e d ass e nt as a p plic a bl e)  is ex ec ut e d b y all p arti es will b e 
c o nsi d er e d t h e p oi nt of e nr oll m e nt f or t his st u dy , a n d t h e s u bj ect will b e assi g n e d a s u bj ect I D n u m b er. 
T h e I C F will b e r e vis e d w h e n e v er i m p ort a nt n e w i nf or m ati o n b ec o m es a v ail a bl e, or t h er e is a n 
a m e n d m e nt t o t h e pr ot oc ol w hic h n ec essit at es a c h a n g e t o t h e I C F. All r evisi o ns t o t h e c o ns e nt f or m 
m ust b e a p pr ov e d i n a dv a nc e by t h e I R B/ E C a n d l oc al r e g ul at ory b o dy, as a p pr o pri at e. T h e s u bj ect 
s h o ul d b e r e-c o ns e nt e d acc or di n g t o I R B/ E C r e q uir e m e nts f oll o wi n g t h e pr oc ess as  d escri b e d a b ov e. If 
r e q uir e d, t h e i n v esti g at or or d esi g n e e s h o ul d r e-c o ns e nt t h e s u bj ect i n a ti m ely m a n n er. 
8. 3.  S u bj e ct  S cr e e ni n g  
All c o ns e nt e d s u bj ects will b e assi g n e d a s u bj ect I D a n d will b e c o nsi d er e d e nr oll e d i nt o t h e st u dy. All 
c o ns e nt e d s u bj ects w h o exit t h e st u dy pri or t o st u dy c o m pl eti o n will h av e t h e r e as o n f or exit 
d oc u m e nt e d o n t h e St u dy Exit c as e r e p ort f or m as w ell as i n t h e m e dic al r ec or d.  
Aft er o bt ai ni n g i nf or m e d c o ns e nt, t h e f oll o wi n g pr oc ess f or p ati e nt scr e e ni n g will b e f oll o w e d:  
1.  T h e st u dy sit e will assi g n a u ni q u e s u bj ect I D n u m b er t o all e nr oll e d (c o ns e nt e d)  s u bj ects. 
2.  T h e s u bj ect will h a v e tr a nst h or acic ec h oc ar di o gr a p hy 2  ( T T E) a n d c ar di ac m a g n etic r es o n a nc e 
( C M R) ex a ms3  t o ass ess p ul m o n ary r e g ur git ati o n a n d R V siz e a n d f u ncti o n, if n ot alr e a d y 
p erf or m e d p er r e q uir e m e nts gi v e n i n 
 
 
 
3.  S u bj ects t h at d o n ot m e et ec h oc ar di o gr a p hic a n d/ or C M R crit eri a will b e exit e d fr o m t h e st u dy. 
S u bj ects  t h at m e et  t h e ec h oc ar di o gr a p hic  a n d  C M R  crit eri a will  u n d er g o  b as eli n e  c ar di ac 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 3  of 1 2 1  
c o m p ut e d t o m o gr a p hy ( C T) a n gi o gr a p hy p er 
 
 
4.  A n at o mic m e as ur e m e nts will b e p erf or m e d b y M e dtr o nic fr o m t h e C T i m a g es a n d e v al u at e d p er 
d e vic e sizi n g g ui d eli n es gi v e n i n 
 
 
5.  It is p ossi bl e t h at s u bj ects d e e m e d eli gi bl e f or i m pl a nt m ay n ot m e et all sizi n g g ui d eli n es d u e t o 
v ari ati o n i n R V O T a n at o m y. T h e i nv esti g at or c a n us e t h e crit eri a d escri b e d i n 
 
 as a g ui d eli n e t o ass ess t h e 
s u bj ect’s c a n di d ac y f or T P V i m pl a nt ati o n 
6.  M e dtr o nic will pr ovi d e t h e sizi n g e v al u ati o n ( p eri m et er pl ot) t o t h e i n v esti g at or. If t h e 
I nv esti g at or c o nsi d ers t h e s u bj ect a n at o mic all y s uit a bl e f or i m pl a nt ati o n of t h e H ar m o ny T P V, 
t h e f oll o wi n g cli nic al i nf or m ati o n fr o m t h e s u bj ect will b e s u b mitt e d t o t h e Scr e e ni n g 
C o m mitt e e:  
a.  Cli nic al ass ess m e nts a n d m e dic al  hist ory  
b.  Ec h oc ar di o gr a p hic, C M R, a n d C T d at a o n a n at o mic al  s uit a bilit y 
7.  T h e Scr e e ni n g C o m mitt e e will r evi e w t h e scr e e ni n g d at a a n d pr ovi d e a r ec o m m e n d ati o n t o t h e 
i nv esti g at or, i ncl u di n g v al v e siz e, w h o will m a k e t h e fi n al d et er mi nati o n of i m pl a nt ati o n 
s uit a bilit y. If it is d et er mi n e d t h e s u bj ect’s a n at o m y is n ot s uit a bl e f or i m pl a nt ati o n, t h e s u bj ect 
will b e exit e d fr o m t h e st u dy. S u bj ects ori gi n ally scr e e n e d f or T P V 2 2 w h o w er e exit e d d u e t o 
scr e e n f ail ur e m a y b e r e-scr e e n e d f or TP V 2 5 or m T P V 2 5 aft er b ei n g r e -c o ns e nt e d. F or t h os e 
su bj ects r e -scr e e n e d, a u ni q u e s u bj ect I D will b e assi g n e d.  
8.  S u bj ects w h o ar e d et er mi n e d t o b e d evic e c a n di d at es by t h e i nv esti g at or ar e eli gi bl e f or c ar di ac 
c at h et eriz ati o n a n d H ar m o ny T P V i m pl a nt ati o n. I m pl a nt att e m pt is c o nsi d er e d t h e p oi nt at 
w hic h t h e i nv esti g ati o n al pr o d uct is i ntr o d uc e d i nt o t h e s u bj ect’s b o dy. I m pl a nt ati o n pr oc e d ur es 
ar e d escri b e d i n t h e I F U  d oc u m e nt.  
8. 4.  H ar m o n y T P V 2 5 R oll -I n  P h a s e  
Pri or t o a n y i m pl a nt of t h e H ar m o ny T P V 2 5, t h er e w ill b e a R oll-I n p h as e t o i ncl u d e a c o h ort of s u bj ects 
f or t h e i m pl a nt of t h e T P V 2 5. 
R oll -i n O bj e cti v e s: 
T h e o bj ectiv e of t h e H ar m o ny T P V 2 5 R oll -I n P h as e is t o c o nfir m t h e pr oc e d ur al f e asi bilit y, h e m o dy n a mic 
p erf or m a nc e a n d s af et y pr ofil e of t h e H ar m o ny  T P V 2 5 pri or t o t h e H ar m o ny T P V 2 5 b ec o mi n g a v ail a bl e 
f or i m pl a nt at all sit es. Als o, t h e R oll-I n p h as e is i nt e n d e d pr ovi d e St u dy Pr oct ors f a mili arity a n d a d d e d 
ex p ertis e i n t h e i m pl a nt t ec h ni q u e f or H ar m o ny T P V 2 5 pri or t o pr oct ori n g all sit es i n i m pl a nt i n g t h e 
H ar m o ny T P V 2 5.  
R oll -i n M et h o d ol o g y: 
S u bj ects e nr oll e d i n t h e R oll -i n p h as e will f oll o w all m et h o ds a n d pr oc e d ur es acc or di n g t o t h e CI P. T his 
s ecti o n will pr ovi d e i nf or m ati o n o n m et h o ds a n d r e q uir e m e nts s p ecific t o t h e R oll -i n p h as e of t h e st u dy. 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 4  of 1 2 1  
R oll -i n P h as e D esi g n: 
T h e R oll -i n p h as e is s p ecific t o t h e i niti al i m pl a nts of t h e H ar m o ny T P V 2 5, t o c o nfir m t h e pr oc e d ur al 
f e asi bilit y, h e m o dy n a mic p erf or m a nc e a n d s af et y pr ofil e of t h e d e vic e b ef or e all sit es c a n i m pl a nt t h e 
H ar m o ny T P V 2 5. T his p h as e  of i niti al H ar m o ny T P V i m pl a nts  will b e li mit e d t o t h e i n v esti g ati v e sit es 
wit h ex p eri e nc e d i m pl a nt ers ( St u dy Pr oct ors).  
I n v esti g ati v e Sit es: 
T h e R oll -i n s u bj ects will b e i m pl a nt e d at u p t o f o ur i nv esti g ativ e sit es w h er e t h e i m pl a nti n g p hysici a n is 
a n ex p eri e nc e d i m pl a nt er a n d is c urr e ntl y pr oct ori n g ot h er sit es o n t h e H ar m o ny T P V i m pl a nt ati o n 
pr oc e d ur e ( St u dy Pr oct or).  
N u m b er of S u bj ects:  
A mi ni m u m of fiv e a n d u p t o ei g ht q u alif yi n g s u bj ects will b e i m pl a nt e d wit h t h e H ar m o ny T P V 2 5 at u p 
t o f o ur St u dy Pr oct or sit es. E ac h St u dy P r oct or sit e c a n i m pl a nt u p t o t hr e e s u bj ects. 
S u bj ect S el ecti o n Crit eri a  
Pr os p ectiv e s u bj ects f or t h e R oll -i n p h as e m ust m e et all s u bj ect s el ecti o n crit eri a f or e nr oll m e nt i n t h e 
M e dtr o nic H ar m o ny T P V Cli nic al St u dy (s e e S ecti o n  7 . S el ecti o n of S u bj ects ). 
I nf or m e d C o ns e nt: 
Pri or t o e nr olli n g i n t h e st u dy, p ati e nts will b e f ull y i nf or m e d of t h e d et ails of st u dy p artici p ati o n i n t h e 
R oll -I n P h as e as r e q uir e d by a p plic a bl e r e g ul ati o ns, t h e sit e’s I R B/E C a n d b y M e dtr o nic.  
Scr e e ni n g a n d E nr oll m e nt:  
S e e S ecti o n 7.  S el ecti o n of S u bj ects f or scr e e ni n g a n d e nr oll m e nt i nf or m ati o n. 
R oll -i n C o h ort A n al y si s: 
T h e pr oc e d ur al f e asi bilit y, a n d h e m o dy n a mic p erf or m a nc e a n d s af et y pr ofi l e at h os pit al disc h ar g e 
f oll o wi n g H ar m o ny T P V 2 5 i m pl a nt ati o n of t h e R oll-I n c o h ort will b e a n alyz e d. T h e o utc o m e m e as ur es 
ar e d efi n e d as:  
Pr oc e d ur al F e asi bilit y:  
•  
N o d evic e - or pr oc e d ur al -r el at e d m ort ality, wit h  
•  
s ucc essf ul acc ess, d eliv ery a n d r e m o v al of t h e d eli v ery s yst e m, a n d  
•  
d e pl o y m e nt a n d c orr ect p ositi o ni n g (i ncl u di n g mi n or r e p ositi o ni n g if n e e d e d ) of t h e d e vic e.  
H e m o d y n a mic P erf or m a nc e:  
•  
M e a n R V O T gr a di e nt ≤ 4 0 m m H g as m e as ur e d b y  ec h oc ar di o gr a p hy  
S af et y Pr ofil e:  
N o n e of t h e f oll o wi n g d e vic e - or pr oc e d ur e -r el at e d s eri o us a d v ers e ev e nts: 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 5  of 1 2 1  
•  
Lif e-t hr e at e ni n g m aj or bl e e d  
•  
M aj or  v asc ul ar  or  c ar di ac str uct ur al c o m plic ati o ns r e q uir e d u n pl a n n e d  r ei nt er v e nti o n or  s ur g ery 
•  
P ul m o n ar y  e m b olis m  
R oll -i n c o h ort s u bj ects will b e f oll o w e d p er t h e CI P. R oll-i n d at a f or t h e f oll o w-u p p h as e will b e i ncl u d e d 
i n t h e 4 0-s u bj ect pi v ot al c o h ort as a ppr ov e d b y F D A.  
If R oll-i n p h as e o utc o m e m e as ur es ar e m et a n d n o c o nc er ns ar e r ais e d by t h e D M C, St e eri n g C o m mitt e e 
or M e dtr o nic, t h e H ar m o ny T P V 2 5 will b e m a d e av ail a bl e t o all p artici p ati n g H ar m o ny T P V st u dy sit es. 
H ar m o ny T P V 2 5 s u bj ects i m pl a nt e d f oll o wi n g t h e R oll -i n p h as e will als o b e i ncl u d e d i n t h e 4 0-s u bj ect 
pi v ot al c o h ort.  
8. 5.  A d diti o n of m T P V 2 5  C o h ort  
F oll o wi n g t h e c o m pl eti o n of t h e 4 0 piv ot al c o h ort of T P V 2 2 a n d T P V 2 5 , t h e T P V 2 5 w as m o difi e d. T h er e 
will b e a n a d d e d c o h ort of u p t o 1 5 s u bj ects i m pl a nt e d wit h t h e m T P V 2 5. T his a d diti o n al c o h ort will 
i ncl u d e 1 0 U S i m pl a nts a n d u p t o 5 O U S i m pl a nts fr o m C a n a d a a n d/ or J a p a n. 
m T P V 2 5 C o h ort O bj e cti v e s:  
T h e o bj ectiv e of t h e  m T P V 2 5 a d diti o n is t o c o nfir m t h e pr oc e d ur al f e asi bility, h e m o dy n a m ic 
p erf or m a nc e, a n d s af et y pr ofil e of t h e m T P V 2 5.  
m T P V 2 5 M et h o d ol o g y:  
S u bj ects e nr oll e d i n t h e m T P V 2 5 c o h ort will f oll o w all m et h o ds a n d pr oc e d ur es acc or di n g t o t h e CI P. 
T his s ecti o n will pr ovi d e i nf or m ati o n o n m et h o ds a n d r e q uir e m e nts s p ecific t o t h e m T P V 2 5 c o h ort 
a d diti o n i nt o t h e st u dy.  
m T P V 2 5 St u d y D esi g n:  
T h e a d diti o n of t h e m T P V 2 5 c o h ort i nt o t h e st u dy will f oll o w t h e s a m e st u dy d esi g n of t h e st u dy 
d escri b e d i n S ecti o n 5. S el ecti o n of S u bj ects . 
I n v esti g ati v e Sit es: 
T h e st u dy sit es i ncl u d e 9 US sit es, 2 C a n a d a sit es, a n d 1 J a p a n sit e.  
N u m b er of S u bj ects:  
T h er e will b e 1 0 U S i m pl a nts a n d u p t o 5 O U S i m pl a nts fr o m C a n a d a a n d/ or J a p a n.  
S u bj ect S el ecti o n Crit eri a  
Pr os p ectiv e s u bj ects f or t h e m T P V 2 5 c o h ort m ust m e et all s u bj ect s el ecti o n crit eri a f or e nr oll m e nt i n 
t h e M e dtr o nic H ar m o ny T P V Cli nic al St u dy (s e e S ecti o n 7 . S el ecti o n of S u bj ects). 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 6  of 1 2 1  
I nf or m e d C o ns e nt: 
Pri or  t o e nr olli n g i n t h e st u dy, p ati e nts will b e f ull y i nf or m e d of t h e d et ails of st u dy p artici p ati o n i n t h e 
m T P V 2 5 c o h ort as r e q uir e d b y a p plic a bl e r e g ul ati o ns, t h e sit e’s I R B/ E C a n d b y M e dtr o nic.  
Scr e e ni n g a n d E nr oll m e nt:  
S e e S ecti o n 7.  S el ecti o n of S u bj ects f or scr e e ni n g a n d e nr oll m e nt i nf or m ati o n. 
m T P V 2 5 C o h ort A n al y si s:  
T h e pr oc e d ur al f e asi bilit y, h e m o dy n a mic p erf or m a nc e, a n d s af et y pr ofil e of m T P V 2 5 at 1 m o nt h 
f oll o wi n g m T P V 2 5 i m pl a nt ati o n will b e a n alyz e d. T h e o utc o m e m e as ur es ar e d efi n e d as:  
Pr oc e d ur al F e asi bilit y:  
•  
N o d evic e - or pr oc e d ur al -r el at e d m ort ality, wit h  
•  
s ucc essf ul acc ess, d eliv ery a n d r e m o v al of t h e d eli v ery s yst e m, a n d  
•  
d e pl o y m e nt a n d c orr ect p ositi o ni n g (i ncl u di n g mi n or r e p ositi o ni n g if n e e d e d) of t h e  d e vi c e. 
H e m o d y n a mic P erf or m a nc e:  
•  
M e a n R V O T gr a di e nt ≤ 4 0 m m H g as m e as ur e d b y  ec h oc ar di o gr a p hy  
S af et y Pr ofil e:  
N o n e of t h e f oll o wi n g d e vic e - or pr oc e d ur e -r el at e d s eri o us a d v ers e ev e nts: 
•  
Lif e-t hr e at e ni n g m aj or bl e e d  
•  
M aj or  v asc ul ar  or  c ar di ac str uct ur al c o m plic ati o ns r e q uir e d u n pl a n n e d  r ei nter v e nti o n  or  s ur g ery 
•  
P ul m o n ar y  e m b olis m  
m T P V 2 5 s u bj ects will b e f oll o w e d p er t h e CI P. A s u p pl e m e nt al a n al ysis f or t h e m T P V 2 5 s u bj ects f or 
o utc o m es of pr oc e d ur al f e asi bilit y, h e m o dy n a mic p erf or m a nc e a n d s af et y pr ofil e will b e p erf or m e d 
s e p ar at ely w h e n m T PV 2 5 s u bj ects h av e b e e n f oll o w e d f or 1 m o nt h.  
8. 6.  I m pl a nt C at h eri z ati o n  Pr o c e d ur e  
C ar di ac c at h et eriz ati o n is p erf or m e d acc or di n g t o t h e st a n d ar d pr oc e d ur es of t h e i nt er v e nti o n al 
c ar di ol o gist. D et ail e d o utli n e of t h e c at h et eriz ati o n pr oc e d ur e r ec o m m e n d ati o ns  is pr ovi d e d i n t h e I F Us 
f or H ar m o ny T P V 2 2, H ar m o ny T P V 2 5, a n d H ar m o ny m T P V 2 5. 
T h e Pri nci p al I nv esti g at or is a ntici p at e d t o b e t h e pri m ar y o p er at or f or t h e i m pl a nt pr oc e d ur e m ust st a y 
c o nsist e nt thr o u g h o ut t h e d ur ati o n of t h e st u dy f or all i m pl a nt e d p a ti e nts at e ac h sit e, u nl ess pri or 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 7  of 1 2 1  
a p pr o v al is r ec ei v e d fr o m M e dtr o nic. S u b -i nv esti g at ors wit h a p pr o pri at e tr ai ni n g a n d ex p eri e nc e m ay 
assist i n t h e i m pl a nt pr oc e d ur e at t h e discr eti o n o f t h e Pri nci p al I nv esti g at or. 
8. 6. 1.  
P o st -Pr o c e d ur e  C ar e  
P ost -pr oc e d ur e c ar e is c arri e d o ut acc or di n g t o t h e st a n d ar d p ost -pr oc e d ur e c ar e of t h e i nt erv e nti o n al 
c ar di ol o gist at his or h er discr eti o n. It is r ec o m m e n d e d i n v esti g at ors c o m ply wit h t h e A H A/ A C C 
g ui d eli n es f or bi o pr ost h etic tiss u e v alv es a n d pr escri b e lif el o n g As piri n t h er a py a n d pr o p hyl actic 
a nti bi otic t h er a py pri or t o d e nt al pr oc e d ur es. 3 5 F or a n y i m a gi n g p erf or m e d (i. e. i ntr ac ar di ac 
ec h oc ar di o gr a p hy, tr a ns es o p h a g e al ec h oc ar di o gr a p hy, or ot h er i m a gi n g) p ost pr oc e d ur e, b ef or e l e a vi n g 
t h e c at h et eriz ati o n l a b, p er st a n d ar d of c ar e at t h e i nv esti g ati o n al sit e, a c o py of t h e i m a gi n g m a y b e 
r e q u est e d by M e dtr o nic f or r e vi e w. 
8. 6. 2.  
Di s c h ar g e  Crit eri a  
F oll o wi n g c o m pl eti o n of Disc h ar g e pr oc e d ur es d escri b e d i n  S ecti o n 8. 1. Sc h e d ul e d of E v e nts , h os pit al 
disc h ar g e will occ ur at t h e discr e ti o n of t h e i nv esti g at or. 
8. 6. 3.  
D e vi c e  E x pl a nt  
I n t h e ev e nt of a m e dic ally i n dic at e d ex pl a nt of t h e H ar m o ny T P V, t h e ex pl a nti n g p hysici a n will f oll o w 
st a n d ar d l oc al ex pl a nt pr oc e d ur es. S u bj ects will b e f oll o w e d t hr o u g h disc h ar g e of t h e ex pl a nt 
h os pit aliz ati o n o r u ntil st u dy cl os ur e, w hic h ev er occ urs first. St u dy sit es s h o ul d att e m pt t o o bt ai n c o pi es 
of a ut o ps y r e p orts a n d t h e d e at h c ertific at e i n t h e ev e nt of a s u bj ect’s d e at h. R e q uir e m e nts s p ecific t o 
ex pl a nt ati o n at r e o p er ati o n or a ut o ps y ar e d escri b e d i n A p p e n di x I X: E X PL A N T P R O T O C OL . T h e 
ex pl a nt e d H ar m o ny T P V s h o ul d b e r et ur n e d t o M e dtr o nic as o utli n e d i n S ecti o n 6. 6 . Pr o d uct R et ur n. 
8. 7.  S u bj e ct  E v al u ati o n s  
S u bj ects i n w h o m t h e H ar m o ny T P V w as i m pl a n t e d will b e e v al u at e d at h os pit al disc h ar ge, o n e m o nt h, 
six m o nt hs, o n e y e ar, a n d a n n u ally t h er e aft er t hr o u g h fi v e y e ars or u ntil t h e H ar m o ny T P V is ex pl a nt e d. 
Pr ot oc ol -r e q uir e d ev al u ati o ns s h o ul d b e p erf or m e d at t h e st u dy sit e w h e n p ossi bl e. E v al u ati o ns to b e 
p erf or m e d ar e s u m m ariz e d i n S ecti o n 8. 1.  Sc h e d ul e of E v e nts . If t h e s u bj ect is s e e n at a cli nic n ot 
ass oci at e d wit h t h e st u dy sit e, all eff orts s h o ul d b e m a d e t o o bt ai n c o pi es of m e dic al r ec or ds fr o m t h at 
visit. D at a o bt ai n e d fr o m t h es e o utsi d e m e dic al r ec or ds c a n b e us e d t o s u p p ort d at a e ntry f or t h at visit.  
8. 7. 1.  
U n pl a n n e d  Vi sit s  
U n pl a n n e d s u bj ect visits t h at ar e n ot d et ail e d i n S ecti o n 8. 1 . Sc h e d ul e of E v e nts a n d ar e d e e m e d 
n ec ess ary i n or d er t o ev al u at e t h e H ar m o ny T P V ar e c o nsi d er e d u n pl a n n e d visits f or t h e p ur p os es of t h e 
pr ot oc ol a n d d o n ot n e e d t o t ak e pl ac e at t h e st u dy sit e. A d diti o n ally, o nly d at a t h at c a n b e o bt ai n e d b y 
t h e st u dy sit es ar e r e q uir e d t o b e r e p ort e d. P ot e nti al r el e v a nt u npl a n n e d pr oc e d ur es i ncl u d e:  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 8  of 1 2 1  
•  
Cli nic al  ass ess m e nt  
•  
Ec h oc ar di o gr a p hy  
•  
C M R  
•  
C T c ar di ac  a n gi o gr a p hy  
•  
R a di o gr a p hy  
8. 7. 2.  
Mi s s e d  Vi sit s  
E v ery eff ort s h o ul d b e m a d e t o e ns ur e s u bj ects r et ur n t o t h e st u dy sit e f or all pr ot oc ol r e q uir e d f oll o w - 
u p visits. If t h e s u bj ect is u n a bl e t o r et ur n f or a n i n -p ers o n cli nic visit, t h e i n v esti g at or, or d esi g n e e, 
s h o ul d d oc u m e nt i n t h e s u bj ect r ec or d t h e r e as o n t h e s u bj ect w as u n a bl e t o c o m pl et e t h e visit a n d, if 
a p plic a bl e, f oll o w t h e r e q uir e m e nts f or d evi ati o n r e p orti n g o utli n e d i n S ec ti o n 8. 1 0. D e vi ati o n H a n dli n g. 
I n t h e c as e t h at t h e s u bj ect will n ot b e s e e n f or a pr ot oc ol r e q uir e d f oll o w-u p visit, t h e i nv esti g at or 
s h o ul d m ak e e v er y eff ort t o c o nt act t h e s u bj ect or s u bj ect’s l e g al r e pr es e nt ati v e wit hi n t h e visit wi n d o w 
t o c oll ect t h e s u bj ect’s vit al st at us as w ell as i nf or m ati o n r el at e d t o p ot e nti al a dv ers e e v e nts, s af ety 
d at a, a n d h os pit aliz ati o ns.  
8. 8.  S u b st a nti al R a di ati o n D o s e  L e v el  
A S u bst a nti al R a di ati o n D os e L e v el ( S R DL) is a n a p pr o pri at el y s el ect e d r ef er e nc e v al u e us e d t o tri g g er 
a d diti o n al d os e m a n a g e m e nt acti o ns d uri n g a pr oc e d ur e a n d m e dic al f oll o w -u p f or a r a di ati o n l e v el t h at 
mi g ht pr o d uc e a cl i nic all y r el e v a nt i nj ur y i n a n a v er a g e p ati e nt. T h er e is n o i m plic ati o n t h at r a di ati o n 
l e v els a b ov e t h e S R DL will al w a ys c a us e a n i nj ury or t h at r a di ati o n l e v els b el o w t h e S R DL will n e v er c a us e 
a n i nj ur y. T h e est a blis h e d S R DL f or t his st u dy is a k er m a -ar e a  pr o d uct of 5 0 0 G y *c m 2. 
W h e n t h e S R DL h as b e e n exc e e d e d, t h e S u bst a nti al R a di ati o n D os e L e v el el ectr o nic c as e r e p ort f or m 
( e C R F) s h o ul d b e c o m pl et e d a n d cli nic al f oll o w -u p is r e q uir e d. T h e s u bj ect s h o ul d b e a dvis e d of t h e 
p ossi bilit y of a s ki n i nj ury d u e t o a tiss u e r e acti o n a n d i nstr uct e d t o ex a mi n e t h e b e a m e ntr a nc e sit e f or 
2 -4 w e e ks p ost -pr oc e d ur e. T h e s u bj ect s h o ul d r e p ort a ny s ki n c h a n g es. I n t h e e v e nt t h e s u bj ect d o es n ot 
c o nt act t h e sit e wit hi n 3 0 d a ys aft er t h e pr oc e d ur e, t h e sit e s h o ul d f oll o w -u p wit h t h e s u bj ect t o ass ess 
if a p ot e nti al ski n i nj ur y h as t a k e n pl ac e.  
If a s ki n i nj ur y is s us p ect e d, t h e s u bj ect s h o ul d b e s e e n at a cli nic visit a n d a p pr o pri at e f oll o w -u p c ar e 
s h o ul d b e d et er mi n e d. I n t h e e v e nt a s ki n i nj ur y occ urs, a n A dv ers e E v e nt e C R F m ust b e c o m pl et e d t o 
d oc u m e nt t h e i nj ur y.  
8. 9.  A s s e s s m e nt of  S af et y  
M et h o ds a n d ti mi n g f or ass essi n g, r ec or di n g, a n d a n alyzi n g s af ety p ar a m et ers ar e ex pl ai n e d i n S ecti o n  
1 0.  A d v ers e E v e nts a n d D e vic e  D efici e nci es . 
A n ext er n al, i n d e p e n d e nt cli nic al e v e nts c o m mitt e e ( C E C) will r e vi e w a n d a dj u dic at e all e n d p oi nt r el at e d 
A Es a n d s u bj ect d e at hs.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 2 9  of 1 2 1  
A n ext er n al, i n d e p e n d e nt d at a m o nit ori n g c o m mitt e e ( D M C) will ass ess i nt eri m st u dy d at a a n d pr o vi d e 
r ec o m m e n d ati o ns t o M e dtr o nic r e g ar di n g st u dy c o n d uct, s h o ul d t h e y i d e ntif y a ny iss u es t h at m ay aff ect 
t h e s af et y of t h e st u dy s u bj ects. 
8. 1 0.  R e c or di n g  D at a  
St u dy sit es will assi g n a u ni q u e s u bj ect I D n u m b er t o e ac h e nr oll e d (c o ns e nt e d) s u bj ect. R ec or ds of t h e 
s u bj ect/s u bj ect I D r el ati o ns hi p will b e m ai nt ai n e d by t h e st u dy sit e. I n di vi d u al s u bj ect m e dic al 
i nf or m ati o n o bt ai n e d as a r es ult of t his st u dy will b e c o nsi d er e d c o nfi d e nti al. 
T his st u dy will utiliz e Or acl e Cli nic al R e m ot e D at a C a pt ur e ( R D C) s yst e m t h at is t h e pr o p ert y of 
M e dtr o nic. R e q uir e d d at a will b e r ec or d e d o n e C R Fs by a ut h oriz e d sit e p ers o n n el as i n dic at e d o n t h e 
D el e g ati o n T as k List ( D TL). St u dy p ers o n n el d el e g at e d f or  e C R F c o m pl eti o n a n d/ or a p pr o v al will b e 
tr ai n e d o n t h e us e of t h e R D C syst e m a nd t h er e aft er pr o vi d e d wit h a u ni q u e us er n a m e a n d p ass w or d t o 
acc ess t h e syst e m. T h e e C RFs m ust b e c o m pl et e d a n d/ or u p d at e d t o r efl ect t h e l at est o bs erv ati o ns o n 
s u bj ects p artici p ati n g i n t h e st u dy. T h e Pri nci p al I nv esti g at or ( or a p pr o pri at el y d el e g at e d s u b- 
i nv esti g at or) will el ectr o nic ally si g n (i. e. a p pr o v e) e ac h e C R F att esti n g t o t h e acc ur ac y of t h e d at a 
pr o vi d e d. T h e R D C syst e m will m ai nt ai n a n a u dit tr ail of e C R F d at a e ntri es a n d c orr ecti o ns. If sit e 
p ers o n n el m ak e c orr ecti o ns t o a pr evi o usly a p pr o v e d e C R F, a n a p pr o pri at ely d el e g at e d i nv esti g at or s h all 
r e-a p pr o v e t his e C R F. D at a fr o m t h e c or e l a b will b e e nt er e d i nt o t h e R D C syst e m b y c or e l a b p ers o n n el 
p er t h eir pr oc e d ur es est a blis h e d f or t h e st u dy.  
All st u dy -r el at e d d oc u m e nts m ust b e r et ai n e d u ntil notifi e d b y M e dtr o nic t h at r et e nti o n is n o l o n g er 
r e q uir e d. M e dtr o nic will i nf or m t h e i n v esti g at or/i nstit uti o n w h e n t h es e d oc u m e nts ar e n o l o n g er 
r e q uir e d t o b e r et ai n e d. 
N o st u dy d oc u m e nt or i m a g e s h o ul d b e d estr o y e d wit h o ut pri or writt e n a gr e e m e nt b et w e e n M e dtr o nic 
a n d t h e i nv esti g at or. S h o ul d t h e i nv esti g at or wis h t o assi g n t h e st u dy r ec or ds t o a n ot h er p art y or m o v e 
t h e m t o a n ot h er l oc ati o n, a dv a nc e writt e n n otic e m ust b e give n t o M e dtr o nic.  
8. 1 1.  D e vi ati o n  H a n dli n g  
A pr ot oc ol d evi ati o n is d ef i n e d as a n occ urr e nc e w h er e t h e st u dy w as n ot c o n d uct e d acc or di n g t o t h e 
pr ot oc ol or t h e I nv esti g at or A gr e e m e nt. Ex a m pl es of pr ot oc ol d e vi ati o ns i ncl u d e b ut ar e n ot li mit e d t o:  
•  
F ail ur e t o o bt a i n i nf or m e d c o ns e nt pri or t o st u dy p artici p ati o n  
•  
I nc orr ect v ersio n of t h e i nf or m e d c o ns e nt f or m  us e d  
•  
F ail ur e t o o bt ai n I R B/ E C a p pr o v al b ef or e t h e st art of t h e  st u dy 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3 0 of 1 2 1  
•  
E nr oll e d s u bj ect di d n ot m e et i ncl usi o n/ excl usi o n  crit eri a 4  
•  
R e q uir e d t esti n g a n d/ or m e as ur e m e nts n ot d o n e or i nc orr ectl y d o n e  
•  
F oll o w -u p visit miss e d or c o m pl et e d o utsi d e  wi n d o w  
•  
U n a ut h oriz e d us e of i n v esti g ati o n al  d evic es  
•  
A dv ers e ev e nts n ot r e p ort e d i n t h e r e q uir e d ti m e fr a m e as d efi n e d b y r e g ul ati o n or t h e  CI P  
•  
C o ntr ol of st u dy d e vic es n ot  m ai nt ai n e d  
•  
S o urc e d at a p er m a n e ntly  l ost 
•  
E nr oll m e nt of p ati e nts d uri n g l a ps e of I R B/ E C  a p pr ov al  
E v ery att e m pt s h o ul d b e m a d e t o a v oi d pr ot oc ol d evi ati o ns. I nv esti g at ors s h o ul d o bt ai n pri or a p pr ov al 
fr o m M e dtr o nic b ef or e i niti ati ng a n y c h a n g e or d e vi ati o n fr o m t h e CI P, exc e p t w h er e n ec ess ary t o 
pr ot ect t h e ri g hts, s af ety or w ell b ei n g of a s u bj ect i n a n e m er g e ncy sit u ati o n. S uc h a p pr o v al s h all b e 
d oc u m e nt e d i n writi n g a n d m ai nt ai n e d i n t h e I nv esti g at or Sit e Fil e. Pri or a p pr o v al is g e n er ally n ot 
ex p ect e d i n sit u ati o ns w h er e u nf or es e e n circ u mst a nc es ar e b e y o n d t h e i n v esti g at or’s c o ntr ol ( e. g., 
s u bj ect di d n ot att e n d sc h e d ul e d f oll o w-u p visit).  
D evi ati o ns will b e r e p ort e d t o M e dtr o nic r e g ar dl ess of w h et h er t h e occ urr e nc e w as m e dic all y j ustifi a bl e, 
pr e -a p pr o v e d b y M e dtr o nic, or t a k e n t o pr ot ect t h e s u bj ect i n a n e m er g e ncy. St u dy d e vi ati o ns s h o ul d b e  
r e p ort e d t o M e dtr o nic vi a t h e St u dy D evi ati o n e C R F.5  
I nv esti g at ors s h o ul d r e p ort t h e f oll o wi n g d evi ati o ns t o M e dtr o nic a n d t h eir r e vi e wi n g I R B/ E C (if r e q uir e d 
by l oc al r e g ul ati o n) wit hi n 5 w or ki n g d ays of t h e occ urr e nc e of t h e d evi ati o ns:  
•  
F ail ur e t o o bt ai n writt e n i nf or m e d  c o ns e nt 
•  
D evi ati o ns t o pr ot ect t h e lif e or p hysic al w ell -b ei n g of a s u bj ect i n a n  e m er g e nc y 
I n a d diti o n, i n v esti g at ors ar e r e q uir e d t o a d h er e t o l oc al I R B/ E C pr oc e d ur es f or r e p orti n g d evi ati o ns. 
M e dtr o nic is r es p o nsi bl e f or a n al yzi n g d e vi ati o ns, ass essi n g t h eir si g nific a nc e, a n d i d e ntif yi n g a n y 
c orr ecti v e a n d/ or pr e v e ntiv e acti o ns t h at m ay b e w arr a nt e d. R e p etitiv e or s eri o us i nv esti g at or 
c o m pli a nc e iss u es m a y r e pr es e nt a n e e d t o i niti at e a c orr ecti v e acti o n pl a n, w hic h m a y i ncl u d e 
s us p e nsi o n of e nr oll m e nt or t er mi n ati o n of t h e i nv esti g at or or sit e’s p artici p ati o n i n t h e st u dy.  
4  S u bj e cts m us t m e et all i n cl usi o n/ e x cl usi o n crit eri a t o b e eli gi bl e f or i m pl a nt ati o n. H o w e v er, it will n ot b e c o nsi d er e d a pr ot o c ol 
d e vi ati o n if n e w st u d y r el at e d t esti n g ( e. g., e c h o, C T c ar di a c a n gi o gr a p h y, or S cr e e ni n g C o m mitt e e ass ess m e nt) of a c o ns e nt e d  
s u bj e ct i d entifi es i m pl a nt ati o n eli gi bilit y crit eri a t h at ar e n ot  m et.  
5  I n t h e c as e of a miss e d st u d y visit or a n o ut of wi n d o w visit ( e. g., f oll o w -u p visit), o n e e C R F is r e q uir e d. A d e vi ati o n e C R F is n ot 
r e q uir e d f or e a c h ass ess m e nt miss e d at o n e visit.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3 1  of 1 2 1  
 
 
 
8. 1 2.  S u bj e ct Wit h dr a w al or  Di s c o nti n u ati o n  
All i m pl a nt e d s u bj ects will b e e nc o ur a g e d t o r e m ai n i n t h e st u dy t hr o u g h t h e fi n al f oll o w -u p visit at 5 
y e ars. S u bj ects w h o disc o nti n u e p artici p ati o n pr e m at ur el y will b e i ncl u d e d i n t h e a n alysis of r es ults ( as 
a p pr o pri at e) a n d wi ll n ot b e r e pl ac e d i n t h e e nr oll m e nt of t ot al st u dy s u bj ects. T h e r e as o n f or 
pr e m at ur e disc o nti n u ati o n s h o ul d b e d oc u m e nt e d i n t h e s u bj ect fil e a n d  vi a t h e St u dy Exit e C R F.  
 
T h e st u dy sit e will m ak e e v er y eff ort t o h av e i m pl a nt e d s u bj ects c o m pl et e t h e f oll o w -u p visit sc h e d ul e. A 
s u bj ect will n ot b e c o nsi d er e d l ost t o f oll o w-u p u nl ess all eff orts t o o bt ai n c o m pli a nc e ar e u ns ucc essf ul. 
At a mi ni m u m, t h e eff ort t o o bt ai n f oll o w -u p i nf or m ati o n m ust i ncl u d e at mi ni m u m 3 att e m pts t o m a k e 
c o nt act vi a t el e p h o n e or e -m ail. If t h es e c o nt act att e m pts ar e n ot s ucc essf ul, a tr ac e a bl e l ett er fr o m t h e 
i nv esti g at or s h o ul d b e s e nt t o t h e s u bj ect’s l ast k n o w n a d dr ess an d t h e s u bj ect’s pri m ar y p hysici a n 
c o nt act e d. S u bj ects will t h e n b e d e e m e d l ost t o f oll o w u p. All c o nt act eff orts t o o bt ai n f oll o w -u p m ust 
b e d oc u m e nt e d i n t h e s u bj ect’s m e dic al  r ec or ds. 
 
If a s u bj ect disc o nti n u es t h e st u dy pr e m at ur ely, is wit h dr a w n fr o m th e st u dy b y t h e i nv esti g at or, or 
c o m pl et es all pr ot oc ol r e q uir e d f oll o w -u p, t h e y s h o ul d c o nti n u e t o b e f oll o w e d by t h e i m pl a nti n g sit e 
acc or di n g t o t h eir r o uti n e cli nic al pr actic e f or p ul m o n ar y v al v e p ati e nts. If, f or a n y r e as o n, t his is n ot 
p ossi bl e, or i f s u bj ect n e e ds t o c h a n g e his/ h er f oll o w-u p sit e at a n y ti m e p oi nt aft er c o ncl usi o n of t h e 
st u dy, i n v esti g at ors s h o ul d r ef er s u bj ects t o a l oc al sit e wit h a p pr o pri at e tr ai ni n g a n d ex p eri e nc e i n 
m a n a gi n g p ati e nts wit h i m pl a nt e d p ul m o n ar y v alv es.  
 
 
9. 1.  P ot e nti al  Ri s k s  
All m at eri als us e d i n t h e H ar m o ny T P V h av e b e e n us e d pr e vi o usl y i n i m pl a nt a bl e m e dic al d e vic es wit h 
lo n g -st a n di n g cli nic al ex p eri e nc e. T h e fr a m e is c o nstr uct e d fr o m niti n ol, w hic h h as b e e n us e d i n 
c or o n ar y a n d p eri p h eral art eri al st e nti n g a p plic ati o ns as w ell as i n tr a nsc at h et er a ortic v alv es wit h 
cli nic all y acc e pt a bl e p erf or m a nc e. Gl ut ar al d a hy d e -fix e d p orci n e tiss u e wit h A O A ® h as b e e n us e d i n 
c o m m erci ally av ail a bl e bi o pr ost h etic h e art v al v es si nc e 1 9 9 2. T h er ef or e, t h e m at eri als us e d i n t h e 
H ar m o ny T P V d o n ot r e pr es e nt u nr e as o n a bl e risks t o p ati e nts.  
 
N o c ar di ac c at h et eriz ati o n pr oc e d ur e c a n b e c o nsi d er e d e ntir ely wit h o ut ris ks, disc o mf ort, distr ess, or 
i nc o nv e ni e nc e. As wit h a ny c ar di ac c at h et eriz ati o n pr oc e d ur e, c ert ain c o m plic ati o ns m ay occ ur t hr o u g h 
p artici p ati o n i n t h e cli nic al st u dy. T h er e m a y b e risks t h at w e d o n ot k n o w y et. T h er e m a y b e risks t h at 
w e d o n ot k n o w h o w oft e n will h a p p e n or h o w s e v er e t h e y will b e w h e n t h ey h a p p e n. T his is b ec a us e 
t h e st u dy is i n t h e e arly p h as e a n d w e d o n ot h a v e m uc h ex p eri e nc e wit h t his d evic e. Alt h o u g h C T t ests 
ar e b ec o mi n g t h e st a n d ar d m et h o d of ass ess m e nt f or tr a n sc at h et er v al v e i m pl a nt ati o n, t h er e is a n 
a d diti o n al ris k of i ncr e as e d r a di ati o n ex p os ur e fr o m t h e r e q uir e d C T t est f or t his cli nic al st u dy.  
9. Ri s k s a n d B e n efit s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3 2  of 1 2 1  
If t h e s u bj ect is a f e m al e of c hil d b e ari n g p ot e nti al, a pr e g n a nc y t est will t ak e pl ac e b ef or e t h e C T t est 
a n d a g a i n b ef or e t h e i m pl a nt pr oc e d ur e t o m a k e s ur e t h e s u bj ect is n ot pr e g n a nt as t h er e m a y b e ris ks 
t o t h e e m bry o or f et us t h at ar e c urr e ntl y u n k n o w n. 
Pl e as e r ef er t o t h e H ar m o ny T P V I F U d oc u m e nt f or a f ull listi n g of risks a n d f urt h er i nf or m ati o n o n t h e 
ris ks of t h e H ar m o ny T P V.  
9. 2.  P ot e nti al  B e n efit s  
T h e pri m ar y p ot e nti al b e n efit of t h e H ar m o ny T P V t o p ati e nts is r est or ati o n of h e m o dy n a mic f u ncti o n of 
his or h er p ul m o n ar y v alv e wit h o ut t h e n e e d f or i nv asiv e c ar di ac s ur g ery. S p ecif ic ally, t h e H ar m o ny T P V 
is i nt e nd e d t o r est or e a n d m ai nt ai n p ul m o n ary v al v e c o m p et e nc e f or p ati e nts wit h p ul m o n ary 
r e g ur git ati o n. R e d ucti o n i n r e g ur git a nt v ol u m e c o ul d r es ult i n i m pr ov e d or pr es erv ati o n of ri g ht 
v e ntric ul ar f u ncti o n, a d ecr e as e i n t h e i nci d e nc e of arr hyt h mi as, a n d a n i m p r ov e m e nt i n eff ort 
t ol er a nc e. T h es e p ot e nti al b e n efits c o ul d d el ay t h e n ext s ur gic al i nt er v e nti o n, i d e ally r e d uci n g t h e 
n u m b er of c ar di ac s ur g eri es a p ati e nt r e q uir es ov er his or h er lif eti m e. A d diti o n all y, d at a g ai n e d fr o m 
t his st u dy m ay b e n efit ot h ers i n t h e f ut ur e. D u e t o t h e r el ati v el y s m all ex p eri e nc e wit h t his d e vic e, t h es e 
b e n efits ar e p ossi biliti es a n d n ot k n o w n f or  c ert ai n. 
9. 3.  Ri s k -B e n efit  R ati o n al e  
T h e H ar m o ny T P V e arly f e asi bilit y st u dy d e m o nstr at e d t h at H ar m o ny T P V i m pl a nt ati o n m a y b e a s af e 
a n d e ff ectiv e tr e at m e nt o pti o n f or p ati e nts wit h r e p air e d c o n g e nit al h e art dis e as e wit h p ul m o n ar y 
r e g ur git ati o n. 
Alt h o u g h t h er e ar e ris ks ass oci at e d wit h i m pl a nt ati o n of t h e H ar m o ny T P V as o utli n e d i n S ecti o n 9. 1.  
P ot e nti al Ris ks , t h e y ar e n ot a ntici p at e d t o b e w ors e t h a n t h e risks ass oci at e d wit h c urr e nt i nt er v e nti o ns 
f or d ysf u ncti o n al p ul m o n ary v alv es, n a m el y s ur gic al r e pl ac e m e nt. T h e p ot e nti al b e n efits of t h e st u dy as 
o utli n e d i n S ecti o n 9. 2.  P ot e nti al B e n efits o ut w ei g h t h e p ot e nti al risks; t h er ef or e, t h e i nv esti g ati o n is 
j ustifi e d. 
T h e f oll o wi n g m e as ur es will b e i m pl e m e nt e d t o mi ni miz e ris ks t o t h e st u dy s u bj ects:  
•  
All s u bj ects will b e acc e pt a bl e s ur gic al  c a n di d at es 
•  
I m pl a nti n g p hysici a ns will h a ve c o nsi d er a bl e ex p eri e nc e i n i nt erv e nti o n al c o n g e nit al c ar di ol o gy 
pr oc e d ur es  
•  
St u dy sit es will h av e c o m pr e h e ns i v e c o n g e nit al c ar di ol o gy a n d s ur g er y pr o gr a ms wit h 
est a blis h e d  c a p acit y f or e m er g e nc y  c at h et eriz ati o n a n d  c ar di ac s ur g ery, if n ec ess ar y  
•  
P ati e nts b ei n g c o nsi d er e d f or t h e st u dy will b e ri g or o usl y  scr e e n e d 
•  
S u bj ects will u n d er g o t h or o u g h ass ess m e nts d uri n g t h eir pr e -i m pl a nt w or k u p  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3 8  of 1 2 1  
1 0. 2. 3.  
Cl a s sifi c ati o n of S eri o u s A d v er s e  E v e nt s  
A ny ev e nt t h at m e ets t h e S A E crit eri a pr ovi d e d i n T a bl e 1: A d v ers e e v e nt d efi niti o ns f or r e p or ti n g 
r e q uir e m e nts is t o b e cl assifi e d as a s eri o us a d v ers e ev e nt ( S A E).  
1 0. 2. 4.  
Cl a s sifi c ati o n of C a u s al  R el ati o n s hi p s  
F or e ac h o bs er v e d A E, t h e c a us al r el ati o ns hi p b et w e e n t h e A E a n d t h e T P V, t h e A E a n d t h e D S, a n d t h e 
A E a n d t h e i m pl a nt pr oc e d ur e will b e c at e g oriz e d as: c a us al r el ati o ns hi p, pr o b a bl e r el ati o ns hi p, p ossi bl e 
r el ati o ns hi p, u nli k el y r el ati o ns hi p, a n d n ot r el at e d, acc or di n g t o t h e d efi niti o ns pr o vi d e d b el o w. 3 7 It 
s h o ul d b e ass u m e d t h er e is a c a us al or pr o b a bl e r el ati o nshi p t o t h e T P V, D S, or i m pl a nt pr oc e d ur e 
u nl ess a n ot h er c a us e is i d e ntifi e d as a p ossi bility.  
C a us al  R el ati o ns hi p  
T h e ev e nt is ass oci at e d wit h t h e T P V, D S, or i m pl a nt pr oc e d ur e  w h e n:  
•  
t h e ev e nt is a k n o w n si d e eff ect of t h e pr o d uct c at e g or y t h e T P V or 
D S b el o n gs t o or of si mil ar d e vic es a n d  pr oc e d ur es;  
•  
th e ev e nt h as a t e m p or al r el ati o ns hi p wit h T P V or D S us e/ a p plic ati o n 
or i m pl a nt  pr oc e d ur e;  
•  
t h e ev e nt i n v ol v es a b o dy-sit e or or g a n t h at 
o  t h e T P V, D S, or i m pl a nt pr oc e d ur e ar e a p pli e d t o; 
o  t h e T P V, D S, or i m pl a nt pr oc e d ur e h av e a n eff ect o n;  
•  
t h e ev e nt f oll o ws a k n o w n r es p o ns e p att er n t o t h e T P V, D S, or 
i m pl a nt pr oc e d ur e (if t h e r es p o ns e p att er n is pr evi o usl y k n o w n);  
•  
t h e disc o nti n u ati o n of T P V or D S a p plic ati o n ( or r e d ucti o n of t h e l ev el 
of acti v ati o n/ ex p os ur e) a n d r ei ntr o d ucti o n of its us e ( or i ncr e as e of 
t h e l ev el of acti v ati o n/ ex p os ur e) h as a n i m p act o n t h e e v e nt ( w h e n 
cli nic all y f e asi bl e); 
•  
ot h er p ossi bl e c a us es ( e. g. a n u n d erl yi n g or c o nc urr e nt ill n ess/ cli nic al 
c o n diti o n or/ a n d a n eff ect of a n ot h er d evic e, dr u g or tr e at m e nt) h av e 
b e e n a d e q u at ely r ul e d  o ut;  
•  
h ar m t o t h e s u bj ect is d u e t o err or i n  us e.  
N ot e: I n or d er t o est a blis h t h e r el at e d n ess, n ot all t h e crit eri a list e d a b o v e 
mi g ht b e m et at t h e s a m e ti m e, d e p e n di n g o n t h e ty p e of i n v esti g ati o n al 
d e vic e/i m pl a n t pr oc e d ur e a n d t h e ev e nt. 
Pr o b a bl e  R el ati o ns hi p  T h e r el ati o ns hi p wit h t h e us e of t h e T P V, D S, or i m pl a nt  pr oc e d ur e s e e ms 
r el e v a nt a n d/ or t h e ev e nt c a n n ot b e ex pl ai n e d by a n ot h er c a us e, b ut 
a d diti o n al i nf or m ati o n m ay b e  o bt ai n e d.  
P ossi bl e  R el ati o ns hi p  
T h e r el ati o ns hi p wit h t h e us e of t h e T P V, D S, or i m pl a nt pr oc e d ur e is w e a k 
b ut c a n n ot b e r ul e d o ut c o m pl et el y. Alt er n ativ e c a us es ar e als o p ossi bl e ( e. g. 
a n u n d erl yi n g or c o nc urr e nt ill n ess/ cli nic al c o n diti o n or/ a n d a n eff ect of 
a n ot h er d e vic e, dr u g or  tr e at me nt).  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 3 9  of 1 2 1  
C as es w h er e r el at e d n ess c a n n ot b e ass ess e d or n o i nf or m ati o n h as b e e n 
o bt ai n e d s h o ul d als o b e cl assifi e d as p ossi bl e.  
U nli k el y R el ati o ns hi p T h e r el ati o ns hi p wit h t h e us e of t h e T P V, D S, or i m pl a nt pr oc e d ur e s e e ms n ot 
r el e v a nt a n d/ or t h e ev e nt c a n be r e as o n a bl y ex pl ai n e d by a n ot h er c a us e, b ut 
a d diti o n al i nf or m ati o n m ay b e o bt ai n e d.  
N ot  r el at e d 
R el ati o ns hi p t o t h e T P V, D S, or i m pl a nt pr oc e d ur e c a n b e excl u d e d  w h e n:  
•  
t h e ev e nt is n ot a k n o w n6  si d e eff ect of t h e pr o d uct c ate g or y t h e 
d e vic e b el o n gs t o or of si mil ar d e vic es a n d  pr oc e d ur es;  
•  
t h e ev e nt h as n o t e m p or al r el ati o ns hi p wit h t h e us e of t h e 
i nv esti g ati o n al d evic e or t h e pr oc e d ur es;  
•  
t h e s eri o us ev e nt d o es n ot f oll o w a k n o w n r es p o ns e p att er n t o t h e 
m e dic al d evic e (if t h e r es p o ns e p att er n is pr evi o usly k n o w n) a n d is 
bi ol o gic ally  i m pl a usi bl e; 
•  
t h e disc o nti n u ati o n of m e dic al d e vic e a p plic ati o n or t h e r e d ucti o n of 
t h e l ev el of acti v ati o n/ ex p os ur e - w h e n cli nic all y f e asi bl e - a n d 
r ei ntr o d ucti o n of its us e ( or i ncr e as e of t h e l e vel of 
ac ti v ati o n/ ex p os ur e), d o n ot i m p act o n t h e s eri o us ev e nt;  
•  
t h e ev e nt i n v ol v es a b o dy-sit e or a n or g a n n ot ex p ect e d t o b e 
aff ect e d b y t h e d evic e or  pr oc e d ur e;  
•  
t h e s eri o us e v e nt c a n b e attri b ut e d t o a n ot h er c a us e ( e. g. a n 
u n d erl yi n g or c o nc urr e nt ill n ess/ cli nic al c o n diti o n, a n eff ect of 
a n ot h er d e vic e, dr u g, tr e at m e nt or ot h er ris k  f act ors); 
•  
h ar ms t o t h e s u bj ect ar e n ot cl e arl y d u e t o us e  err or;  
•  
I n or d er t o est a blis h t h e n o n-r el at e d n ess, n ot all t h e crit eri a list e d 
a b o v e mi g ht b e m et at t h e s a m e t i m e, de p e n di n g o n t h e t y p e of 
d e vic e/ pr oc e d ur es a n d t h e s eri o us  ev e nt.  
1 0. 2. 5.  
R e p orti n g of D e vi c e  D efi ci e n ci e s  
D evic e d efici e nc y i nf or m ati o n will b e c oll ect e d t hr o u g h o ut t h e st u dy a n d r e p ort e d t o M e dtr o nic. D evic e 
d efici e nci es t h at l e d t o a n A E ar e r e p ort e d o n t h e A E e C R F. D e vic e d efici e nci es t h at di d n ot l e a d t o a n A E 
s h o ul d b e r e p ort e d o n a D evic e D efici e ncy e C R F ( o n e f or e ac h d evic e d efici e ncy).  
6 W h e n t h e e v e nt is n ot a k n o w n si d e eff e ct of t h e pr o d u ct c at e g or y t h e d e vi c e b el o n gs t o or of si mil ar d e vi c es a n d pr o c e d ur es, it 
g e n er all y is c o nsi d er e d “ n ot r el at e d”. Y et, t h e u n e x p e ct e d eff e ct s h all n ot b e e x cl u d e d fr o m e v al u ati o n a n d r e p orti n g.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 0 of 1 2 1  
 
 
 
1 0. 3.  A nti ci p at e d A d v er s e  E v e nt s  
A ntici p at e d A Es f or s u bj ects p artici p ati n g i n t h e st u dy ar e o utli n e d i n S ecti o n 9. 1 . P ot e nti al Ris ks. 
F urt h er i nf or m ati o n is pr o vi d e d i n t h e I nv esti g at or’s Br oc h ur e a n d I F U.  
 
1 0. 4.  E m er g e n c y C o nt a ct D et ail s f or R e p orti n g S A E, U A D E,  a n d 
D e vi c e  D efi ci e n ci e s  
I nv esti g at ors s h o ul d c o nt act t h e M e dtr o nic st u dy m a n a g er or sit e ma n a g er if t h ey h a v e a ny q u esti o ns 
r e g ar di n g r e p ort a bl e A Es. M e dtr o nic will m ai nt ai n a listi n g of c urr e nt st u dy c o nt act d et ails a n d pr ovi d e 
t o e ac h sit e 
 
 
1 1. 1.  S cr e e ni n g  C o m mitt e e  
•  
A Scr e e ni n g C o m mitt e e will b e us e d t o e ns ur e p ati e nt s el ecti o n is a p pr o pri at e a n d  c o nsist e nt 
a m o n g tri al sit es. T h e r ol e of t h e Scr e e ni n g C o m mitt e e will i ncl u d e t h e f oll o wi n g: C o nfir m ati o n 
t h at s u bj ects m e et i ncl usi o n / excl usi o n crit eri a 
•  
C o nfir m ati o n t h at s u bj ects ar e a n at o mic all y s uit a bl e f or H ar m o ny T P V  i m pl a nt 
T h e Scr e e ni n g C o m mitt e e will b e c o m pris e d of a s u bs et of st u dy i n v esti g at ors wit h ex p ertis e i ncl u di n g:  
•  
C o n g e nit al H e art  Dis e as e  
•  
I nt er v e nti o n al C ar di ol o gy  
•  
C ar di ac  S ur g ery  
•  
C ar di ac  I m a gi n g 
 
1 1. 2.  Cli ni c al E v e nt s  C o m mitt e e  
A Cli nic al E v e nts C o m mitt e e ( C E C) will pr ovi d e i n d e p e n d e nt m e dic al r evi e w a n d a dj u dic ati o n of a d v ers e 
e v e nt d at a us e d i n t h e s af et y ass ess m e nt of t h e i nv esti g ati o n al d evic e. T h e C E C will a dj u dic at e, at a 
mi ni m u m, all d e at hs a n d e n d p oi nt r el at e d a d v ers e ev e nts, as o utli n e d i n t h e C E C c h art er. A ny r el at e d 
s o urc e d oc u m e ntati o n pr ovi d e d t o t h e S p o ns or f or C E C r e vi e w a n d a dj u dic ati o n will b e d e -i d e ntifi e d. All 
eff orts s h o ul d b e m a d e by t h e PI t o pr ovi d e s o urc e d oc u m e nt ati o n f or r e vi e w as r e q u est e d by t h e C E C. 
I n t h e ev e nt s o urc e d oc u m e nt ati o n c a n n ot b e o bt ai n e d, a s u m m ary of t h e ev e nt a n d r el at e d cli nic al 
fi n di n gs m a y b e pr ovi d e d by t h e PI. 
 
T h e a n al ysis of t h e st u dy s af et y d at a will b e b as e d o n C E C a dj u dic ati o ns. T h e C E C m e m b ers will b e fr e e 
fr o m bi as t o w ar ds t h e st u dy a n d will b e i n d e p e n d e nt fr o m t h e st u dy i nv esti g at ors a n d M e dtr o nic. T h e 
c o m mitt e e will c o nsist of at l e ast 3 i n d e p e n d e nt ex p erts ( n o n -M e dtr o nic e m pl o y e d p hysici a ns ) wit h 
ex p ertis e r el e v a nt t o t h e st u dy. T his m a y i ncl u d e ex p eri e nc e i n t h e ar e as of:  
1 1.  D at a R e vi e w C o m mitt e e s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 1  of 1 2 1  
•  
C o n g e nit al H e art  Dis e as e  
•  
I nt er v e nti o n al C ar di ol o gy  
•  
C ar di ac  S ur g ery  
1 1. 3.  D at a M o nit ori n g  C o m mitt e e  
A D at a M o nit ori n g C o m mitt e e ( D M C) will ass ess i nt eri m st u dy d at a a n d pr ovi d e r ec o m m e n d ati o ns t o 
M e dtr o nic r e g ar di n g st u dy c o n d uct, s h o ul d t h ey i d e ntif y a ny iss u es t h at m ay aff ect t h e s af et y of t h e 
st u dy s u bj ects. D M C m e m b ers will b e fr e e fr o m bi as t o w ar ds t h e st u dy a n d will b e i n d e p e n d e nt fr o m 
t h e st u dy i n v esti g at ors, a n d M e dtr o nic. T h e D M C will c o nsist of a mi ni m u m of 3 m e m b ers w h o m a y 
h a v e ex p eri e nc e i n t h e ar e as of:  
•  
C o n g e nit al H e art  Dis e as e  
•  
I nt er v e nti o n al C ar di ol o gy  
•  
C ar di a c S ur g ery  
T h e D M C will m e et (vi a t el ec o nf er e nc e or i n p ers o n) t o est a blis h pr oc e d ur es f or s af et y d at a r e vi e w, c h air 
a p p oi nt m e nt, a n d g ui d eli n es f or st u dy r ec o m m e n d ati o ns. T h e D M C will m e et o n a p eri o dic b asis t o 
p er f or m a c o m pr e h e nsi v e d at a r evi e w, i ncl u din g at a mi ni m u m, all S A Es a n d d e at hs, a n d will m e et m or e 
fr e q u e ntl y w h e n n e e d e d. S af et y-r el at e d e n d p oi nts m ay als o b e r e vi e w e d at t h es e m e eti n gs. D M C 
m e eti n gs m a y c o nsist of b ot h o p e n a n d cl os e d s essi o ns. M e dtr o nic p ers o n n el m ay f acilit at e t h e D M C 
m e eti n g b ut will n ot h a v e v oti n g privil e g es.  
F oll o wi n g e ac h m e eti n g, t h e D M C will r e p ort t o M e dtr o nic i n writi n g a n d m a y r ec o m m e n d c h a n g es i n 
t h e c o n d uct of t h e st u dy. T h e D M C r ec o m m e n d ati o ns m a y i ncl u d e r ec o m m e n d ati o ns o n st u dy st at us 
s uc h as c o nti n ui n g t h e st u dy wit h o ut m o dific ati o ns, c o nti n ui n g t h e st u dy wit h m o dific ati o ns, st o p pi n g or 
s us p e n di n g e nr oll m e nt, or r ec o m m e n d ati o ns r e g ar di n g st u dy c o n d uct i ncl u di n g r ec o m m e n d ati o ns 
ar o u n d e nr oll m e nt or pr ot oc ol d evi ati o ns.  
I n t h e c as e of U A D Es, if M e dtr o nic a n d t h e D M C d et er mi n e t h at t h e ev e nt pr es e nts a n u nr e as o n a bl e risk 
t o t h e p artici p ati n g s u bj ects, M e dtr o nic m ust t er mi n at e t h e cli nic al st u dy wit hi n 5 w or ki n g d ays aft er 
m a ki n g t h at d et er mi n ati o n a n d n o l a t er t h a n 1 5 w or ki n g d a ys aft er M e dtr o nic first r ec ei v es n otic e of t h e 
eff ect. All st u dy sit es will b e n otifi e d of t his acti o n.  
T h e D M C m ay c all a d diti o n al m e eti n gs if, at a ny ti m e, t h er e is c o nc er n a b o ut a ny as p ect of t h e st u dy. All 
d at a pr es e nt e d at t h e m e eti n gs will b e c o nsi d er e d c o nfi d e nti al.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 2  of 1 2 1  
 
 
 
 
 
T h e pri m ar y a n alysis f or s af et y a n d eff ecti v e n ess will b e p erf or m e d w h e n t h e first 4 0 i m pl a nt e d s u bj ects 
h a v e c o m pl et e d t h eir 6 -m o nt h f oll o w -u p. 7  A s u p pl e m e nt al a n al ysis will b e p erf or m e d w h e n t h e 1 0 U S 
i m pl a nts of m T P V 2 5 c o h ort h a v e c o m pl et e d t h eir 1-m o nt h f oll o w -u p. B ot h c o h orts will b e p o ol e d f or 
a d diti o n al a n al ysis o ut t o 5 y e ars aft er t h e pr e vi o usl y m e nti o n e d a n a lys es ar e c o m pl et e d. 
 
1 2. 1.  A n al y si s  S et s  
T h e a n al ysis s u bs ets ar e d efi n e d as f oll o ws:  
 
E nr oll e d C o h o rt 
T h e e nr oll e d c o h ort c o nsists of all e nr oll e d s u bj ects. S u bj ects ar e c o nsi d er e d e nr oll e d at t h e p oi nt of 
si g ni n g t h e I nf or m e d C o ns e nt F or m. 
 
C at h et eriz e d C o h ort  
T h e c at h et eriz e d c o h ort c o nsists of all s u bj ects w h o u n d er g o c at h et eriz ati o n f or p ossi bl e i m p l a nt ati o n of 
t h e H ar m o ny T P V. 
 
Att e m pt e d I m pl a nt C o h ort  
T h e att e m pt e d i m pl a nt c o h ort c o nsists of all s u bj ects w h o u n d er g o c at h et eriz ati o n a n d a  H ar m o ny T P V 
i m pl a nt ati o n w as att e m pt e d ( H ar m o ny T P V is i ntr o d uc e d i nt o t h e s u bj ect’s b o dy). 
 
I m pl a nt e d C o h ort 
T h e i m pl a nt e d c o h ort c o nsists of all s u bj ects w h o u n d er g o c at h et eriz ati o n a n d a H ar m o ny T P V w as 
i m pl a nt e d. 
 
I m pl a nt e d > 2 4 h o urs C o h ort 
T h e i m pl a nt e d > 2 4 h o urs c o h ort c o nsists of all s u bj ects w h o h a v e a H ar m o ny T P V i m pl a nt e d w hic h 
r e m ai ns i m pl a nt e d f or gr e ater t h a n 2 4 h o urs.  
 
1 2. 2.  Pri m ar y  O bj e cti v e s  
T h e pri m ar y o bj ecti v es ar e d escri pti v e, a n d n o st atistic al hy p ot h esis t est will b e p erf or m e d. T h er e is n o 
s a m pl e siz e c alc ul ati o n f or t h e pri m ar y o bj ecti v es. T h e a n alysis p o p ul ati o n will i ncl u d e d at a fr o m t his 
st u dy i n c o m bi n ati o n wit h t h e d at a fr o m t h e N ati v e O utfl o w Tr act Tr a nsc at h et er P ul m o n ary V alv e 
R es e arc h Cli nic al St u dy (I D E # G 1 2 0 1 7 5).  
 
7 W hil e t h e pri m ar y s af et y e n d p oi nt is m e as ur e d at 3 0 d a ys, pri m ar y o bj e cti v e a n al ysis will b e c o m pl et e d u p o n c o m pl eti o n of t h e  
pri m ar y effi c a c y e n d p oi nt, w hi c h is m e as ur e d at 6 m o nt hs.  
1 2.  St ati sti c al D e si g n a n d M et h o d s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 3  of 1 2 1  
T h e a n al ysis f or pri m ar y o bj ectiv es will b e p erf or m e d w h e n all s u bj ects h av e r e ac h e d t h eir 6-m o nt h 
e n d p oi nt. 8  
1 2. 2. 1.  
Pri m ar y S af et y  E n d p oi nt  
T h e pri m ar y s af ety e n d p oi nt  is fr e e d o m fr o m pr oc e d ur e or d e vic e-r el at e d m ort alit y. 
C E C a dj u dic at e d d at a will b e us e d t o ass ess t h e s af ety e n d p oi nt.  
T h e  a n al ysis c o h ort will b e t h e c at h et eriz e d c o h ort. T h e e n d p oi nt will b e d escri b e d b y K a pl a n -M ei er 
st atistics. T h e l o gl o g tr a nsf or m e d t w o-si d e d 9 5 % c o nfi d e nc e i nt erv al usi n g t h e P et o st a n d ar d err or at 3 0 
d a ys will b e pr es e nt e d. T h e pri m ary s af et y o bj ectiv e w ill b e m et if t h e p oi nt esti m at e of t h e fr e e d o m 
fr o m pr oc e d ur e or d evic e-r el at e d m ort ality r at e at 3 0 d a ys p ost-pr oc e d ur e is e q u al t o or gr e at er t h a n 
t h e p erf or m a nc e t ar g et of 9 5 %.  
1 2. 2. 2.  
Pri m ar y Effi c a c y  E n d p oi nt  
T h e pri m ar y effic acy e n d p oi nt is p erc e nt a g e of s u bj ects wit h acc e pt a bl e h e m o dy n a mic f u ncti o n 
c o m p osit e at 6 m o nt hs as d efi n e d b y: 
•  
M e a n R V O T gr a di e nt as m e as ur e d by c o nti n u o us -w av e  D o p pl er ec h oc ar di o gr a p hy ≤4 0 
m m H g  
o  If a c at h et eriz ati o n is p erf or m e d f or cli nic al p ur p os es, t h e c at h et eriz atio n p e a k 
gr a di e nt m e as ur e m e nt will s u p ers e d e t h e c o nti n u o us -w a v e D o p pl er 
ec h oc ar di o gr a p hy m e as ur e m e nt a n d b e us e d t o s u p p ort t h e pri m ary e n d p oi nt. 
A cc e pt a bl e h e m o dy n a mic f u ncti o n as m e as ur e d by c at h et eriz ati o n will b e c o nsi d er e d 
t o b e p e a k gr a di e nt ≤4 0 m m H g . 
-A N D - 
•  
P ul m o n ar y r e g ur git a nt fr acti o n as m e as ur e d by m a g n etic r es o n a nc e i m a gi n g  < 2 0 %  
o  If m a g n etic r es o n a nc e i m a gi n g is c o ntr ai n dic at e d, a c o nti n u o us-w a v e D o p pl er 
ec h oc ar di o gr a p hy m e as ur e m e nt will b e us e d t o s u p p ort t h e pri m ary e n d p oi nt. 
Acc e pt a bl e h e m o dy n a mic f u ncti o n as m e as ur e d by c o nti n u o us -w a v e D o p pl er 
ec h oc ar di o gr a p hy will b e c o nsi d er e d t o b e < m o d er at e p ul m o n ar y  r e g ur git ati o n. 
C or e l a b d at a wi ll b e us e d t o ass ess t h e effic acy e n d p oi nt, wit h a n exc e pti o n i n t h e c as e t h at a 
c at h et eriz ati o n is p erf or m e d t o m e as ur e m e a n R V O T gr a di e nt, i n w hic h sit e r e p ort e d d at a will b e 
utiliz e d.  
8 W hil e t h e pri m ar y s af et y e n d p oi nt is m e as ur e d at 3 0 d a ys, pri m a r y o bj e cti v e a n al ysis will b e c o m pl et e d u p o n c o m pl eti o n of t h e 
pri m ar y effi c a c y e n d p oi nt, w hi c h is m e as ur e d at 6 m o nt hs.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 4  of 1 2 1  
T h e a n al ysis c o h ort f or t h e pri m ar y effic acy e n d p oi nt will b e t h e i m pl a nt e d > 2 4 h o urs c o h ort. T h e 
p erc e nt a g e of s u bj ects wit h acc e pt a bl e h e m o dy n a mic f u ncti o n at 6 m o nt hs a n d a t w o -si d e d 9 5 % 
Cl o p p er -P e ars o n i nt erv al wil l b e pr ovi d e d. T h e pri m ary effic ac y o bj ectiv e will b e m et if t h e p oi nt 
esti m at e is e q u al t o or gr e at er t h a n t h e p erf or m a nc e t ar g et of 7 5 %.  
1 2. 3.  A d diti o n al O ut c o m e  M e a s ur e s  
T e c h nic al s ucc ess at e xit fr o m c at h et eriz ati o n l a b/ o p er ati n g r o o m ( O R)  
T ec h nic al s ucc ess  is d efi n e d as: 
•  
N o d evic e - or pr oc e d ur al -r el at e d m ort ality, wit h  
•  
S ucc essf ul acc ess, d eli v er y a n d r etri ev al of t h e d eliv ery s yst e m,  a n d  
•  
D e pl oy m e nt a n d c orr ect p ositi o ni n g (i ncl u di n g mi n or r e p ositi o ni n g if n e e d e d) of t h e 
si n gl e i nt e n d e d d evic e, a n d  
•  
N o n e e d f or a d diti o n al u n pl a n n e d or e m er g e ncy s ur g er y or r e -i nt er v e nti o n r el at e d t o t h e 
d e vic e or acc ess  pr oc e d ur e  
T h e a n al ysis c o h ort f or t ec h nic al s ucc ess will b e t h e att e m pt e d i m pl a nt c o h ort. T h e p erc e nt a g e of 
s u bj ects wit h t ec h nic al s ucc ess will b e pr es e nt e d. If a n el e m e nt of t h e c o m p osit e is missi n g a n d av ail a bl e 
el e m e nts m e et t h e s ucc ess crit eri a, t h e s u bj ect will b e excl u d e d fr o m t h e a n al ysis.  
D e vic e s ucc ess o ut t o 5 y e ars  
D evic e s ucc ess is d efi n e d as:  
•  
N o d evic e - or pr oc e d ur al -r el at e d m ort ality, wit h  
•  
Ori gi n al i nt e n d e d d evic e i n pl ac e,  a n d  
•  
N o a d diti o n al s ur gic al or i nt er v e nti o n al pr oc e d ur es r el at e d t o acc ess or t h e d e vic e si nc e 
c o m pl eti o n of t h e ori gi n al pr oc e d ur e (i. e., exit  fr o m t h e c at h et eriz ati o n l a b), a n d  
•  
I nt e n d e d p erf or m a nc e of t h e d e vic e, as d efi n e d  as:  
o  Str uct ur al p erf or m a nc e: N o mi gr ati o n, e m b oliz ati o n, d et ac h m e nt, m aj or st e nt 
fr act ur e, h e m ol ysis, t hr o m b osis, e n d oc ar ditis, a n d  
o  H e m o dy n a mic p erf or m a nc e: R eli ef of i ns uffi ci e nc y ( P R < m o d er at e) wit h o ut 
pr o d uci n g t h e o p p osit e ( m e a n R V O T gr a di e nt > 4 0 m m H g) as m e as ur e d by 
c o nti n u o us-w a v e D o p pl er ec h oc ar di o gr a p hy 9, a n d  
•  
A bs e nc e of p ar a -d evic e c o m plic ati o ns, as d efi n e d  by:  
o  P VL ≥ m o d er at e,  or  
o  Er osi o n,  or  
o  R V O T or P A  r u pt ur e 
9 If a c at h et eriz ati o n is p erf or m e d f or cli ni c al p ur p os es, t h e c at h et eri z ati o n p e a k gr a di e nt m e as ur e m e nt will s u p ers e d e t h e 
c o nti n u o us -w a v e D o p pl er e c h o c ar di o gr a p h y m e as ur e m e nt a n d b e u s e d t o s u p p ort t h e  o ut c o m e m e as ur e.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 5  of 1 2 1  
T h e a n al ysis c o h ort f or pr oc e d ur al s ucc ess wil l b e t h e att e m pt e d i m pl a nt c o h ort. T h e e n d p oi nt will b e 
d escri b e d by K a pl a n -M ei er st atistics. T h e l o gl o g tr a nsf or m e d t w o -si d e d 9 5 % c o nfi d e nc e i nt erv al usi n g 
t h e P et o st a n d ar d err or at 6 m o nths ( 1 8 3 d a ys), 1 y e ar ( 3 6 5 d ays), 2 y e ars ( 7 3 0 d a ys), 3 y e ars ( 1 0 9 5  
d a ys), 4 y e ars ( 1 4 6 0 d a ys) a n d 5 y e ars ( 1 8 2 5 d a ys) will b e pr es e nt e d.  
Pr oc e d ur al s ucc ess at 3 0 d a ys  
Pr oc e d ur al s ucc ess is d efi n e d as:  
•  
D evic e s ucc ess at 3 0 d a ys,  a n d  
•  
N o n e of t h e f oll o wi n g d e vic e - or pr oc e d ur e -r el at e d s eri o us a d v ers e ev e nts:  
o  Lif e-t hr e at e ni n g m aj or bl e e d  
o  M aj or v asc ul ar or c ar di ac str uct ur al c o m plic ati o ns r e q uir e d u n pl a n n e d 
r ei nt erv e nti o n or s ur g er y 
o  St a g e 2 or 3 ac ut e ki d n e y i nj ur y ( A KI) (i ncl u d es n e w  di al ysis)  
o  P ul m o n ar y  e m b ol is m 
o  S e v er e h e art f ail ur e ( H F) or h y p ot e nsi o n r e q uiri n g I V i n otr o p e, ultr afiltr ati o n, or 
m ec h a nic al circ ul at ory  s u p p ort 
o  Pr ol o n g e d i nt u b ati o n > 4 8  h o urs  
T h e a n al ysis c o h ort f or pr oc e d ur al s ucc ess will b e t h e att e m pt e d i m pl a nt c o h ort. T h e p erc e nt a g e of 
s u bj ects wit h pr oc e d ur al s ucc ess will b e pr es e nt e d. If a n ele m e nt of t h e c o m p osit e is missi n g a n d 
a v ail a bl e el e m e nts m e et t h e s ucc ess crit eri a, t h e s u bj ect will b e excl u d e d fr o m t h e a n al ysis.  
Fr e e d o m fr o m T P V d ysf u ncti o n o ut t o 5 y e ars  
T P V dysf u ncti o n is d efi n e d  as a n y o n e of t h e f oll o wi n g:  
•  
R V O T r e o p er ati o n f or d e vic e-r el at e d r e as o ns 
•  
C at h et er r e -i nt er v e nti o n of T P V  
•  
H e m o dy n a mic dysf u ncti o n of t h e T P V ( m o d er at e or gr e at er p ul m o n ar y r e g ur git ati o n, a n d/ or 
a m e a n R V O T gr a di e nt > 4 0  m m H g)  
T h e a n al ysis c o h ort will b e t h e i m pl a nt e d l o n g er t h a n 2 4 h o urs c o h ort. T h e e n d p oi nt will b e d escri b e d b y 
K a pl a n -M ei er st atistics. T h e l o gl o g tr a nsf or m e d t w o -si d e d 9 5 % c o nfi d e nc e i nt erv al usi n g t h e P et o 
st a n d ar d err or at 6 m o nt hs ( 1 8 3 d ays), 1 y e ar ( 3 6 5 d a ys), 2 y e ars ( 7 3 0 d ays), 3 y e ar s ( 1 0 9 5 d ays), 4 y e ars 
( 1 4 6 0 d a ys) a n d 5 y e ars ( 1 8 2 5 d ays) will b e pr es e nt e d.  
Ass ess m e nt of s af et y  
Ass ess m e nt of s af ety is d efi n e d as ass ess m e nt of:  
•  
All pr oc e d ur e -r el at e d s eri o us a d v ers e e v e nts  
•  
All d e vic e -r el at e d s eri o us a dv ers e ev e nts  
•  
D e at h ( all -c a us e, pr oc e d ur al, a n d d e vic e -r el at e d) 
F or ass ess m e nt of s af ety, t h e C E C d at a will b e us e d f or a n al ysis. T h e a n al ysis c o h orts ar e:  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 6  of 1 2 1  
 
 
 
•  
All pr oc e d ur e -r el at e d a d v ers e ev e nts: C at h et eriz e d c o h ort 
•  
All d e vic e -r el at e d a d v ers e e v e nts: Att e m pt e d I m pl a nt c o h ort 
•  
D e at h ( all -c aus e, pr oc e d ur al, a n d d e vic e -r el at e d): C at h et eriz e d c o h ort 
A dv ers e ev e nts will b e a n alyz e d eit h er vi a s urvi v al a n al ysis usi n g t h e K a pl a n -M ei er m et h o d or 
s u m m ariz e d b y c o u nt a n d p erc e nt as a p pr o pri at e. 
 
C h ar act eriz ati o n  of q u alit y of lif e sc or es o v er ti m e  
Q u alit y  of lif e sc or e ov er ti m e will b e ass ess e d b y t h e S F -3 6 at pr e -i m pl a nt, 1 m o nt h p ost-i m pl a nt, 6 
m o nt hs p ost -i m pl a nt, a n d a n n u ally p ost-i m pl a nt o ut t o 5 y e ars. T h e a n al ysis c o h ort will b e t h e 
i m pl a nt e d > 2 4 h o urs c o h ort. 
 
S u m m ary st atistics s uc h as m e a n , st an d ar d d evi ati o n, mi ni m u m, m e di a n, a n d m axi m u m will b e pr o vi d e d 
f or q u alit y of lif e sc or es o v er ti m e as ass ess e d by t h e S F-3 6 at pr e -i m pl a nt, 1 m o nt h p ost-i m pl a nt, 6 
m o nt hs p ost -i m pl a nt, a n d a n n u ally p ost-i m pl a nt o ut t o 5 y e ars. 
 
C h ar act eriz ati o n  of ri g ht v e ntricl e r e m o d eli n g f oll o wi n g T P V i m pl a nt as ass ess e d vi a C M R  
Ri g ht v e ntricl e r e m o d eli n g will b e ass ess e d vi a C M R at pr e -i m pl a nt, 6 m o nt hs p ost-i m pl a nt, 2 y e ars p ost- 
i m pl a nt, a n d 5 y e ars p ost-i m pl a nt. T h e a n alysis c o h ort will b e i m pl a nt e d l o n g er t h a n 2 4 h o urs c o h ort.  
S u m m ary st atistics s uc h as m e a n, st a n d ar d d evi ati o n, mi ni m u m, m e di a n, a n d m axi m u m will b e pr o vi d e d 
f or c o nti n u o us v ari a bl es a n d c o u nt a n d p erc e nt a g e will b e pr ovi d e d f or c at e g oric al v ari a bl es. 
 
Fi n al A n al ysis  
Fi n al a n al ysis o n t h e a d diti o n al o utc o m e m e as ur es will b e p erf or m e d w h e n t h e i m pl a nt e d s u bj ects h av e 
r e ac h e d t h eir 5 y e ar e n d p oi nts, wit h t h e exc e pti o n of t h e f oll o wi n g e n d p oi nts, w hic h will b e a n alyz e d i n 
c o nj u ncti o n wit h t h e pri m ar y o bj ectiv e a n alysis ( w h e n all i m pl a nt e d s u bj ects h a v e r e ac h e d t h eir 6 - 
m o nt h visit):  
•  
T ec h nic al s ucc ess at exit fr o m c at h et eriz ati o n l a b/ o p er ati n g r o o m  ( O R) 
•  
Pr oc e d ur al s ucc ess at 3 0  d ays  
 
 
1 3. 1.  St at e m e nt ( s ) of  C o m pli a n c e  
T his st u dy w as d esi g n e d t o r efl ect t h e G o o d Cli nic al Pr actic e ( G C P)  pri nci pl es o utli n e d i n I S O 1 4 1 5 5: 2 0 1 1. 
T h es e i ncl u d e t h e pr ot ecti o n of t h e ri g hts, s af ety a n d w ell -b ei n g of h u m a n s u bj ects, c o ntr ols t o e ns ur e 
t h e sci e ntific c o n d uct a n d cr e di bilit y of t h e cli nic al i nv esti g ati o n a n d t h e d efi niti o n of r es p o nsi biliti es of 
th e s p o ns or a n d i nv esti g a t ors. 
 
T h e st u dy will b e c o n d uct e d acc or di n g t o f e d er al, n ati o n al a n d l oc al l a ws, r e g ul ati o ns, st a n d ar ds, a n d 
r e q uir e m e nts of t h e c o u ntri es/ g e o gr a p hi es w h er e t h e st u dy is b ei n g c o n d uct e d, i ncl u di n g d at a 
pr ot ecti o n l a ws, t h e Cli nic al  St u dy A gr e e m e nt a n d t h e  CI P. T h e st u dy will als o b e c o n d uct e d i n  
1 3.  Et hi c s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 7  of 1 2 1  
acc or d a nc e wit h t h e D ecl ar ati o n of H elsi nki. T h e pri nci pl es of t h e D ecl ar ati o n of H elsi n ki ar e 
i m pl e m e nt e d i n t his st u dy by m e a ns of t h e P ati e nt I nf or m e d C o ns e nt (I C) pr oc ess, I R B/ E C a p pr ov al, 
st u dy tr ai ni n g, clinic al st u dy r e gistr ati o n, pr e -cli nic al t esti n g, ris k b e n efit ass ess m e nt, a n d p u blic ati o n 
p olic y.  
I n t h e U nit e d St at es, t h e st u dy will b e c o n d uct e d u n d er a n F D A I nv esti g ati o n al D e vic e Ex e m pti o n (I D E) i n 
c o m pli a nc e wit h 2 1 C o d e of F e d er al R e g ul ati o ns ( C F R) P arts 1 1, 5 0, 5 4, 5 6 a n d 8 1 2. I n C a n a d a, t h e st u dy 
will b e c o n d uct e d u n d er a n I nv esti g ati o n al T est i n g A ut h oriz ati o n i n c o m pli a nc e wit h S O R/ 9 8-2 8 2 S ecti o n 
7 9 -8 8. I n J a p a n, t h e st u dy will b e c o n d uct e d i n acc or d a nc e wit h t h e J a p a n G C P Or di n a nc e a n d t h e 
P h ar m a c e utic al a n d M e dic al D evic e Act. I n a d diti o n, t h e st u dy will b e c o n d uct e d i n c o m pli a nc e wit h 2 1 
C F R P arts 1 1 a n d 5 4 i n all p artici p ati n g g e o gr a p hi es.  
R e g ul at ory a ut h ority n otific ati o n/ a p pr ov al t o c o n d uct t h e st u dy is r e q uir e d. I nv esti g ati o n al sit es will n ot 
b e activ at e d, n or b e gi n e nr olli n g s u bj ects, u ntil t h e r e q uir e d a p pr o v al fr o m t h e r e g ul at ory a g e ncy a n d 
I R B/ E C h as b e e n o bt ai n e d. A d diti o n ally, a ny r e q uir e m e nts i m p os e d b y a l oc al r e g ul at or y a g e ncy or 
I R B/ E C s h all b e f oll o w e d, as a p pr o pri at e. 
T his st u dy  will b e p u blicl y r e gist er e d pri or t o first e nr oll m e nt i n acc or d a nc e wit h t h e 2 0 0 7 F o o d a n d Dr u g 
A d mi nistr ati o n A m e n d m e nts Act ( F D A A A) a n d D ecl ar ati o n of H elsi n ki o n htt p://cli nic altri als. g o v  ( PL 1 1 0- 
8 5, S ecti o n 8 1 0( a)).  
1 3. 2.  I n stit uti o n al R e vi e w B o ar d / Et hi c s  C o m mitt e e  
T h e st u dy will b e c o n d uct e d i n acc or d a nc e  wit h t h e r e q uir e m e nts of e ac h i n v esti g ati o n al sit e’s I R B/ E C. 
T h e r es p o nsi bl e I R B/ E C m ust a p pr ov e t h e CI P a n d I nf or m e d C o ns e nt f or m pri or t o i m pl e m e nt ati o n.  
S t u dy activiti es will n ot c o m m e nc e pri or t o r ec ei pt of d oc u m e nt ati o n of I R B/ E C a p pr o v al by t h e sit e a n d 
M e dtr o nic. T h e i nv esti g at or a n d st u dy st aff m ust c o m pl y wit h t h e r e q uir e m e nts of t h eir I R B/ E C.  
Pri or t o e nr olli n g s u bj ects, e ac h st u dy sit e’s I R B/ E C wil l b e r e q uir e d t o a p pr ov e t h e c urr e nt CI P, t h e 
I nf or m e d C o ns e nt f or m, a n d a n y ot h er writt e n i nf or m ati o n t o b e pr ovi d e d t o t h e s u bj ects. St u dy sit es i n 
t h e U nit e d St at es m ust als o utiliz e I R B a p pr ov e d H e alt h I ns ur a nc e P ort a bilit y a n d Acc o u nt a bility Act 
( HI P AA) A ut h oriz ati o n.  
I R B/ E C a p pr ov al of t h e st u dy m ust b e r ec eiv e d i n t h e f or m of a l ett er a n d pr ovi d e d t o M e dtr o nic b ef or e 
c o m m e nc e m e nt of t h e st u dy at a n i nv esti g ati o n al sit e. T h e a p pr ov al l ett er m ust c o nt ai n e n o u g h 
i nf or m ati o n t o i d e ntif y t h e v ersi o n or dat e of t h e d oc u m e nts a p pr ov e d. I n a d diti o n t o t h e a p pr o v al 
l ett er, a n I R B/ E C r ost er or l ett er of c o m pli a nc e m ust b e s u b mitt e d t o M e dtr o nic t o all o w v erific ati o n 
t h at t h e i n v esti g at or, ot h er c e nt er st u dy st aff, a n d/ or M e dtr o nic p ers o n n el ar e n ot m e m b ers of t h e 
I R B/ E C. If t h ey ar e m e m b ers of t h e I R B/ E C, writt e n d oc u m e nt ati o n is r e q uir e d st ati n g t h at h e/s h e di d 
n ot p artici p at e i n t h e a p pr o v al pr oc ess. I n v esti g at ors m ust i nf or m M e dtr o nic of a ny c h a n g e i n st at us of  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 8  of 1 2 1  
I R B/ E C a p pr ov al o nc e t h e i nv esti g ati o n sit e has st art e d e nr oll m e nt. If a n y acti o n is t a k e n b y a n I R B/ E C 
wit h r es p ect t o t h e s t u dy, t h at i nf or m ati o n m ust b e f or w ar d e d t o M e dtr o nic. 
1 3. 3.  R e g ul at or y  S u b mi s si o n s  
E ac h st u dy sit e m ust f ulfill all l oc al r e g ul at or y r e q uir e m e nts pri or t o e nr olli n g s u bj ects. E ac h st u dy sit e 
m ust h av e writt e n d oc u m e nt ati o n of sit e/i nv esti g at or r e a di n ess, i ncl u di n g b ut n ot li mit e d t o I R B/ E C 
a p pr o v al of t h e c urr e nt v ersi o n of t h e CI P, I C F, a si g n e d I nv esti g at or’s A gr e e m e nt, c urr e nt i nv esti g at or 
c urric ul u m vit a e ( C V), a n d d oc u m e nt ati o n  of tr ai ni n g. T h e pri nci p al i nv esti g at ors a n d t h eir i nstit uti o ns 
s h all a gr e e t o t his CI P a n d a ny a m e n d m e nts a n d i n dic at e t h eir a p pr ov al by si g ni n g a n d d ati n g t h e Cli nic al 
St u dy A gr e e m e nt.  
I n t h e U nit e d St at es a n d C a n a d a, e ac h st u dy sit e is r e q uir e d t o h a ve a c o py of t h e a p pr o v al l ett er fr o m 
t h e r es p ectiv e g e o gr a p hy’s r e g ul at ory a g e ncy pri or t o t h eir first s u bj ect e nr oll m e nt. M e dtr o nic will 
o bt ai n a c o py of t h e a p pr ov al l ett er fr o m t h e r e g ul at or y a g e nci es.  
Ot h er d oc u m e nts r ef err e d t o i n t his CI P ar e list e d  as f oll o ws a n d will b e m a d e a v ail a bl e u p o n r e q u est:  
•  
M o nit ori n g  Pl a n  
•  
D at a M a n a g e m e nt  Pl a n  
•  
St atistic al A n alysis  Pl a n  
•  
Cli nic al S af ety M a n a g e m e nt a n d P ot e nti al C o m pl ai nts  Pl a n  
•  
El ectr o nic C as e R e p ort F or ms  ( e C R Fs) 
If a r e g ul at or y a g e nc y i m p os es a ny a d diti o n al r e q uir e m e nts ( e. g. s af ety r e p orts, pr o gr ess r e p orts, etc.), 
M e dtr o nic will pr e p ar e t h e r e q uir e d d oc u m e nts a n d s e n d t h e m t o t h e a p plic a bl e r e g ul at ory a g e ncy.  
A ny r evisi o ns or a m e n d m e nts t o t h e CI P, R e p orts of Pri or I nv esti g ati o ns, or I nf or m e d C o ns e nt t e m pl a t e 
d oc u m e nts will b e s u b mitt e d t o t h e r e g ul at or y a g e nci es. A fi n al r e p ort w ill b e s u b mitt e d t o t h e 
r e g ul at ory a g e nci es, if r e q u est e d, u p o n st u dy cl os ur e. 
1 3. 4.  Et hi c al C o n d u ct of t h e  St u d y  
T h e st u dy will b e c o n d uct e d i n acc or d a nc e wit h t h e d esi g n a n d s p ecific p r ovisi o ns of t his pr ot oc ol, i n 
acc or d a nc e wit h t h e et hic al pri nci pl es t h at h av e t h eir ori gi n i n t h e D ecl ar ati o n of H elsi n ki, a n d t h at ar e 
c o nsist e nt wit h G C P, l oc al l a ws a n d t h e a p plic a bl e r e g ul at or y r e q uir e m e nts. T h e st u dy will b e gi n i n e ac h 
g e o gr a p hy o nl y w h e n all t h e r e q uir e m e nts of t h e a p pr o pri at e r e g ul at or y a ut h ority h a v e b e e n f ulfill e d. 
T h e pri nci pl es of t h e D ecl ar ati o n of H elsi nki h a v e all b e e n i m pl e m e nt e d by m e a ns of t h e p ati e nt 
I nf or m e d C o ns e nt pr oc ess, I R B/ E C a p pr ov al, st u dy tr ai ni n g, cli nic al st udy r e gistr ati o n, pr ecli nic al t esti n g, 
ris k b e n efit ass ess m ent, a n d p u blic ati o n p olic y.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 4 9  of 1 2 1  
 
 
 
 
 
1 4. 1.  Sit e  A cti v ati o n  
All l oc al a n d r e gi o n al r e g ul ati o n r e q uir e m e nts will b e f ulfill e d pri or t o sit e acti v ati o n a n d e nr oll m e nt of 
s u bj ects i nt o t h e st u dy. E ac h i n v esti g ati o n al sit e m ust h a v e writt e n i n d oc u m e nt ati o n of sit e re a di n ess, 
i ncl u di n g b ut n ot li mit e d t o: 
 
•  
I R B a p pr ov al l ett er 
•  
F ully ex ec ut e d Cli nic al Tri al A gr e e m e nt  ( C T A) 
•  
Fi n a nci al Discl os ur e f or  I nv esti g at ors 
•  
D el e g at e d T as k  List 
•  
Tr ai ni n g  d oc u m e nt ati o n  
 
1 4. 2.  M o nit ori n g  
I nv esti g ati o n al sit es will b e m o nit or e d t o e ns ur e c o m pli a nc e wit h t h e st u dy pr ot oc ol, a d h er e nc e t o 
a p plic a bl e r e g ul ati o ns, a n d acc ur ac y of st u dy d at a. A m o nit ori n g visit will b e c o n d uct e d pri m arily t o 
e ns ur e t h e s af et y a n d w ell -b ei n g of t h e s u bj ects is pr es er v e d. M o nit ori n g visits will als o b e us e d t o v erify 
th at st u dy d at a s u b mitt e d o n c as e r e p ort f or ms ar e c o m pl et e a n d acc ur at e wit h r es p ect t o t h e s u bj ect 
cli nic al r ec or ds a n d t o v erify d evic e acc o u nt a bilit y. Sit e p ers o n n el will c o m pl et e e C R Fs f oll o wi n g e ac h 
s u bj ect visit. St u dy d at a s u b mitt e d will b e r evi e w e d a g ai nst s u bj ect c h arts a n d ot h er s o urc es c o nt ai ni n g 
ori gi n al r ec or ds of s u bj ect d at a. S o urc e d oc u m e nt v erific ati o n will occ ur i n acc or d a nc e t o t h e M o nit ori n g 
Pl a n. T h e i nv es ti g at or a n d/ or i nstit uti o n s h all p er mit M e dtr o nic m o nit ori n g r e pr es e nt ativ es dir ect acc ess 
t o s o urc e d at a a n d d oc u m e nts. All m o nit ori n g activiti es s h all b e d oc u m e nt e d p er t h e m o nit ori n g pl a n. I n 
J a p a n, t h e m o nit or will c o nfir m p eri o dic t esti n g, c ali br ati o n a n d m ai nt e n a nc e of e q ui p m e nt us e d f or 
st u dy ass ess m e nts acc or di n g t o l oc al st a n d ar d of pr actic e. 
 
It is r ec o m m e n d e d f or all m e dic al r ec or ds t o b e cl e arl y m ar k e d t o i n dic at e t h at t h e s u bj ect is e nr oll e d i n 
t his st u dy. 
 
T h e pr o gr ess of t h e st u dy will b e m o n it or e d b y: 
•  
O n -sit e r e vi e w, a n d/ or r e m ot e d at a cl arific ati o n a n d v erific ati o n, as d e e m e d a p pr o pri at e b y 
M e dtr o nic  
•  
T el e p h o n e c o m m u nic ati o ns b et w e e n t h e sit e p ers o n n el ( e. g., i nv esti g at or, st u dy c o or di n at or) 
a n d st u dy  m o nit ors  
•  
R e vi e w of e C R Fs a n d t h e ass oci at e d cli nic al  r ec or ds 
•  
R e vi e w of r e g ul at ory  d oc u m e nts  
1 4.  St u d y A d mi ni str ati o n  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 0 of 1 2 1  
M o nit ori n g a n d m o nit ori n g ov ersi g ht will b e pr ovi d e d by M e dtr o nic. R e pr es e nt ati v es of M e dtr o nic (i. e. 
c o ntr act ors a n d d esi g n e es) m ay als o act as st u dy m o nit ors.  
1 4. 2. 1.  
Pr e -St u d y  Vi sit s  
Pri or t o e nr oll m e nt, M e d tr o nic p ers o n n el will visit t h e st u dy sit e(s) t o v erify t h e i nv esti g at or a n d 
f aciliti es ar e pr e p ar e d f or t h e st u dy a n d t h at r e q uir e m e nts f or st u dy i niti ati o n w er e c o m pl et e d or i n 
pr o gr ess at t h e ti m e of t h e visit.  
1 4. 2. 2.  
I nt eri m  M o nit ori n g  
T h e st u dy will b e m o ni t or e d t hr o u g h o ut its c o urs e. Fr e q u e nc y of m o nit ori n g visits will b e d et er mi n e d o n 
a c as e -by -c as e b asis.  T h e m o nit or m ay v erify t h e f oll o wi n g d uri n g m o nit ori n g visits:  
•  
T h e st u dy is b ei n g c o n d uct e d acc or di n g t o t h e pr ot oc ol a n d a p plic a bl e  r e g ul ati o ns 
•  
C h a n g e s t o t h e pr ot oc ol r e q uiri n g I R B/ E C r e vi e w h av e b e e n  a p pr o v e d  
•  
Acc ur at e, c o m pl et e, a n d c urr e nt r ec or ds ar e b ei n g  m ai nt ai n e d  
•  
A p pr o v e d i nf or m e d c o ns e nt f or ms ar e b ei n g c o m pl et e d c orr ectly (i ncl u di n g d oc u m e nt ati o n t h at 
t h e s u bj ect w as giv e n a m pl e ti m e t o r e vi e w t h e c o ns e nt, t h at a c o py of t h e c o ns e nt was giv e n t o 
e ac h s u bj ect, a n d t h at n o st u dy pr oc e d ur es occ urr e d pri or t o  c o ns e nt) 
•  
T h e c o ns e nt pr oc ess is b ei n g d oc u m e nt e d  c orr ectl y 
•  
Ti m ely r e p orts ( a n n u al r e p orts, a d v ers e e v e nts, pr ot oc ol d evi ati o ns) ar e b ei n g m a d e t o t h e 
s p o ns or a n d I R B/ E C as r e q uir e d 
In a d diti o n, t h e f oll o wi n g acti viti es m a y occ ur d uri n g m o nit ori n g visits:  
•  
C as e r e p ort f or m  r evi e w 
•  
I nf or m e d c o ns e nt r e vi e w 
•  
I nv esti g ati o n al pr o d uct acc o u nt a bilit y r evi e w 
•  
R e vi e w of d evic e st or a g e  l oc ati o n 
1 4. 2. 3.  
St u d y  Cl o s e -O ut  
A fi n al visit t o t h e c e nt er m a y b e m a d e at st u dy c o ncl usi o n or at t h e e n d of t h e sit e’s p artici p ati o n. 
T h e f oll o wi n g it e ms m ay b e v erifi e d d uri n g t h e cl os e o ut pr oc ess:  
•  
I nv esti g at or/st u dy a d mi nistr ati o n fil es ar e c o m pl et e a n d acc ur at e  
•  
Fi n al r ec ei pt of e C R Fs c o nfir m e d; missi n g d at a or cl arifi c ati o n iss u es cl os e d 
•  
A n n u al a n d i nt eri m r e p orts (if a ny) ar e u p t o  d at e  
•  
R e p ort e d d efici e nci es f or t h e sit e h a v e b e e n r es ol v e d or  cl os e d 
•  
I nv esti g ati o n al pr o d uct acc o u nt a bilit y ( e. g. dis p ositi o n l o gs) b al a nc e a n d ar e c urr e nt 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 1  of 1 2 1  
•  
Sc h e d ul e d et er mi n e d f or fi n al st u dy r e p ort s u b missi o n b y i nv esti g at or t o t h e r es p ecti v e  I R B/ E C 
•  
R ec or d r et e nti o n r e q uir e m e nts disc uss e d a n d a gr e e d t o by t h e  i nv esti g at or 
Aft er t h e st u dy h as b e e n c o m pl et e d, m e dic al c ar e will b e pr ovi d e d t o t h e s u bj ec ts u p o n t h e discr eti o n of 
t h e tr e ati n g p hysici a n. 
1 4. 3.  A u diti n g  
M e dtr o nic m ay c o n d uct a u dits at p artici p ati n g st u dy sit es. T h e p ur p os e of a n a u dit is t o v erify t h e 
p erf or m a nc e of t h e m o nit ori n g pr oc ess a n d t h e st u dy c o n d uct, i n d e p e n d e nt of t h e p ers o n n el dir ect l y 
i nv olv e d i n t h e st u dy. R e g ul at ory b o di es, s uc h as t h e F o o d a n d Dr u g A d mi nistr ati o n, H e alt h C a n a d a or 
P M D A m a y als o p erf or m i ns p ecti o ns at p artic i p ati n g sit es. T h e i nv esti g at or a n d/ or i nstit uti o n s h all 
p er mit M e dtr o nic a n d r e g ul at ory b o di es dir ect acc ess  t o s o urc e d at a a n d d oc u m e nts. 
1 4. 4.  S o ur c e  D at a / D o c u m e nt s  
S o urc e d at a/ d oc u m e nt ati o n is d efi n e d as t h e first ti m e t h e d at a a p p e ar a n d m ay i ncl u d e all cli nic al 
r ec or ds, h os pit al r ec or ds, pr oc e d ur al r e p orts, a ut o psy r e p orts, a n d a n y ot h er m at eri al t h at c o nt ai ns 
o ri gi n al i nf or m ati o n us e d f or st u dy d at a c oll ecti o n or a dv ers e ev e nt r e p orti n g. D at a e nt er e d i nt o t h e 
st u dy d at a b as e m ust b e tr ac e a bl e t o s o urc e d oc u m e nts. 
T h e e C R Fs m a y n ot s erv e as s o urc e d oc u m e nts. S o urc e d oc u m e nt ati o n f or d at a el e m e nts n ot r o uti n ely 
c apt ur e d i n m e dic al r ec or ds ( e g, ec h oc ar di o gr a p hy v ari a b l es, i n v esti g at or ass ess m e nt of a d v ers e e v e nts, 
r e as o n f or st u dy exit, r e as o n f or st u dy d evi ati o ns) m ay v ary fr o m c e nt er t o c e nt er. F or ex a m pl e, t h e sit e 
m a y us e t ec h nic al w or ks h e ets if t h e y ar e cl e arly  i d e ntifi e d as s o urc e d oc u m e nts a n d si g n e d a n d d at e d by 
t h e p ers o n c o m pl eti n g t h e w or ks h e et a n d a st u dy i n v esti g at or. 
S o urc e d oc u m e nts ar e r e q uir e d t o b e m ai nt ai n e d f oll o wi n g t h e r ec or d r et e nti o n p olici es o utli n e d i n 
S ecti o n 1 5. 3 . R ec or d R et e nti o n. S o urc e d oc u m e nts m ust b e m a de av ail a bl e f or m o nit ori n g or a u diti n g 
by t h e s p o ns or’s r e pr es e nt ati v e or r e pr es e nt ativ es of a p plic a bl e r e g ul at or y a g e nci es or t h e I R B/ E C.  
T h e i nv esti g at or m ust e ns ur e t h e a v ail a bility of all s o urc e d o c u m e nts fr o m w hic h d at a o n t h e e C R Fs 
w er e d eri v e d. W h e r e pri nt o uts of el ectr o nic m e dic al r ec or ds ( E M R) ar e pr o vi d e d as s o urc e d oc u m e nts, 
or w h er e c o pi es of m e dic al r ec or ds ar e r et ai n e d as s o urc e d oc u m e nts, t h e y m ust b e i d e ntifi e d as 
c ertifi e d c o pi es t h at foll o w a d oc u m e nt e d c ertific ati o n pr oc ess attri b uti n g t o t h eir acc ur acy a n d 
c o m pl et e n ess. 
I n a d diti o n, t h e m e dic al r ec or ds of st u dy s u bj ects s h o ul d b e m ark e d i n s uc h a w a y t o i n dic at e t h eir 
p artici p ati o n i n t h e st u dy.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 2  of 1 2 1  
1 4. 5.  C o nfi d e nti alit y  
All i nf or m ati o n a n d d at a s e nt t o p arti es i n v ol v e d i n st u dy c o n d uct c o nc er ni n g s u bj ects or t h eir 
p artici p ati o n i n t his st u dy will b e c o nsi d er e d c o nfi d e nti al. St u dy sit es will assi g n a u ni q u e s u bj ect 
i d e ntific ati o n n u m b er (I D) t o e ac h s u bj ect. R ec or ds of t h e s u bj ect/I D r el ati o ns hi p will b e m ai nt ai n e d by 
t h e st u dy sit e. T h e I D is t o b e r ec or d e d o n all st u dy d oc u m e nts t o li n k t h e m t o t h e s u bj ect’s m e dic al 
r ec or ds at t h e sit e. T o m ai nt ai n c o nfi d e nti alit y, t h e s u bj ect’s n a m e or a n y ot h er p ers o n al i d e ntifi ers 
s h o ul d n ot b e r ec or d e d on a ny st u dy d oc u m e nt ot h er t h a n t h e i nf or m e d c o ns e nt f or m. I n t h e e v e nt a 
s u bj ect’s n a m e is i ncl u d e d f or a n y r e as o n, it will b e m as k e d as ap plic a bl e. I n t h e e v e nt of i n a bilit y t o 
m as k t h e i d e ntific ati o n ( e. g., di git al m e di a), it will b e h a n dl e d i n a c o nfi d e nti al m a n n er by t h e a ut h oriz e d 
p ers o n n el.  
St u dy i nf or m ati o n a n d d at a m ay b e s h ar e d wit h t h e f oll o wi n g f or r e as o ns i ncl u di n g, b ut n ot li mi t e d t o, 
m o nit ori n g or a u diti n g p ur p os es:  
•  
Wit h t h e st u dy s p o ns or, M e dtr o nic a n d its a g e nts a n d c o ntr act ors (t o g et h er  “ M e dtr o nic”); 
•  
Wit h ot h er r es e arc h ers i n t h e st u dy t o s u p p ort st u dy c o n d uct or pr oc ess es ( e. g., p ati e nt 
scr e e ni n g); 
•  
Wit h g ov er n m e nt or g a niz a ti o ns a n d r e vi e w b o ar ds r e q uir e d t o w atc h ov er t h e s af et y a n d 
eff ectiv e n ess of m e dic al pr o d ucts a n d t h er a pi es a n d t h e  c o n d uct of r es e arc h; a n d  
•  
Wit h ot h er p ers o ns w h o ar e r e q uir e d t o w atc h ov er t h e s af et y a n d eff ecti v e n ess of m e dic al 
pr o d ucts a n d t h er a pi es a n d t h e c o n d uct of r es e arc h. 
T h e pri v ac y of e ac h s u bj ect a n d c o nfi d e nti alit y of his/ h er i nf or m ati o n s h all b e pr es erv e d i n r e p orts a n d 
w h e n p u blis hi n g a n y d at a.  
I nv esti g ati o n al sit es will pr ot ect t h e p ers o n al i nf or m ati o n of s u bj ects i n acc or d a nc e wit h a p plic a bl e l a ws, 
r e g ul ati o ns a n d I R B/ E C r e q uir e m e nts. 
1 4. 6.  D at a  M a n a g e m e nt  
M e dtr o nic will b e r es p o nsi bl e f or t h e pr oc essi n g a n d q u alit y c o ntr ol of t h e d at a. D at a r e vi e w, d at a b as e 
cl e a ni n g a n d iss ui n g a n d r es ol vi n g d at a q u eri es will b e d o n e acc o r di n g t o M e dtr o nic i nt er n al st a n d ar d 
o p er ati n g pr oc e d ur es ( S O Ps) a n d t h e D at a M a n a g e m e nt Pl a n f or t his st u dy. T h e st u dy d at a b as e will 
e m pl o y v ali d ati o n pr o gr a ms ( e. g. r a n g e a n d l o gic c h ecks) o n c ert ai n e nt er e d d at a t o i d e ntif y p ossi bl e 
d at a e ntry err ors a n d t o f acilit at e d at a v ali d ati o n. R e q uir e d i m a g es f or M e dtr o nic or C or e L a b e v al u ati o n 
will b e d e -i d e ntifi e d a n d el ectr o nic all y tr a nsf erre d usi n g a s ec ur e fil e tr a nsf er or ot h er s ec ur e m et h o ds 
as a p pr o pri at e. All st u dy i m a gi n g i ncl u di n g pr ot oc ol r e q uir e d as s ess m e nts, i m pl a nt a n gi o gr a p hy, a n d a ny 
u nsc h e d ul e d i m a gi n g p erf or m e d t o ass ess t h e H ar m o ny T P V s h o ul d b e s e nt t o  M e dtr o nic.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 3  of 1 2 1  
1 4. 7.  Li a bilit y  
S u bj ect c o m p e ns ati o n, i n d e m nific ati o n a n d li a bility i ns ur a nc e c o v er a g e ar e i ncl u d e d I n t h e Cli nic al St u dy 
A gr e e m e nt f or e ac h p artici p ati n g c e nt er . 
M e dtr o nic m ai nt ai ns a p pr o pri at e cli nic al st u dy li a bility i ns ur a nc e c o v er a g e as r e q uir e d u n d er a p plic a bl e 
l aws a n d r e g ul ati o ns a n d will c o m pl y wit h a p plic a bl e l oc al l a w a n d c ust o ms c o nc er ni n g s p ecific 
i ns ur a nc e c o v er a g e. If r e q uir e d, a cli nic al st u dy i ns ur a nc e st at e m e nt/c ertific at e will b e pr o vi d e d t o t h e 
I R B/ H e a d of M e dic al I nstit uti o n. 
1 4. 8.  C I P  A m e n d m e nt s  
T h e i nv e sti g at or m ay pr o p os e a ny a p pr o pri at e m o dific ati o n(s) of t h e CI P or i n v esti g ati o n al d evic e or 
i nv esti g ati o n al d evic e us e. M e dtr o nic will r evi e w t his pr o p os al a n d d eci d e w h et h er t h e m o dific ati o n(s) 
will b e i m pl e m e nt e d.  
M e dtr o nic will s u b mit a ny si g nific a nt a m e n d m e nt t o t h e CI P, i ncl u di n g a j ustific ati o n f or t h e 
a m e n d m e nt, t o t h e a p plic a bl e r e g ul at o r y a g e nc y(i es) a n d t o t h e i n v esti g at ors t o o bt ai n a p pr ov al fr o m 
t h eir I R B/ E C. T h e i nv esti g at or will o nly i m pl e m e nt t h e a m e n d m e nt aft er r ec ei vi n g a p pr o v al fr o m t h e 
I R B/ E C, a p plic a bl e r e g ul at or y a g e nci es a n d M e dtr o nic. A d mi nistr ativ e a m e n d m e nts t o t h e CI P will b e 
s u b mitt e d t o t h e I R B/ E C f or n otific ati o n. 
1 4. 9.  P u bli c ati o n a n d U s e of  I nf or m ati o n  
M e dtr o nic is c o m mitt e d t o t h e wi d es pr e a d diss e mi n ati o n of all pri m ar y a n d a d dit i o n al e n d p oi nt r es ults. 
A P u blic ati o n Pl a n will b e i m pl e m e nt e d a n d f oll o w e d. At t h e c o ncl usi o n of t h e st u dy, a m ultisit e a bstr act 
r e p orti n g t h e pri m ar y r es ults will b e pr e p ar e d b y t h e Pri nci p al I nv esti g at or (i n c oll a b or ati o n wit h ot h ers) 
f or s u bs e q u e nt pr es e nt ati o n at a n a n n u al sci e ntific m e eti n g. A m ultisit e p u blic ati o n will si mil arly b e 
pr e p ar e d  f or p u blic ati o n i n a r e p ut a bl e sci e ntific j o ur n al. T h e p u blic ati o n of t h e pri nci p al r es ults fr o m 
a ny si n gl e sit e ex p eri e nc e wit hi n t h e st u dy is n ot all o w e d u ntil b ot h t h e pr e p ar ati o n a n d p u blic ati o n of 
t h e m ultisit e r es ults, a n d t h e n o nl y wit h writt e n p ermissi o n fr o m M e dtr o nic.  
F oll o wi n g a n alysis a n d pr es e nt ati o n of t h e e n d p oi nt r es ults, activ e p artici p ati o n of all p artici p ati n g 
i nv esti g at ors, C E C c o m mitt e e m e m b ers, D M C m e m b ers, a n d c or e l a b or at or y p ers o n n el will b e s olicit e d 
f or d at a a n alysis a n d a bstr act a n d m a n uscri pt pr e p ar ati o n. S u b missi o n of all a bstr acts a n d p u blic ati o ns 
fr o m t h e st u dy r e q uir es a p pr o v al by t h e st e eri n g c o m mitt e e a n d p u blic ati o n c o m mitt e e. 
A  s e p ar at e P u blic ati o n Pl a n will pr ovi d e d et ail e d i nf or m ati o n a b o ut t h e p u blic ati o n c o m mitt e e,  
a ut h ors hi p, p u blic ati o n pr o p os als, a n d r e q u ests f or d at a.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 4  of 1 2 1  
 
 
 
1 4. 1 0.  
S u s p e n si o n or E arl y T er mi n ati o n of t h e  St u d y  
M e dtr o nic m ay d eci d e t o s us p e n d or pr e m at ur el y t er mi n at e t h e st u dy. If t h e st u dy is t er mi n at e d 
pr e m at ur el y or s us p e n d e d, M e dtr o nic s h all pr o m ptly i nf or m t h e cli nic al i n v esti g at ors a n d r e g ul at or y 
a ut h oriti es of t h e t er mi n ati o n or s us p e nsi o n a n d t h e r e as o n(s) f or t his. T h e i nv esti g at or s h all t h e n 
pr o m ptly i nf or m t h e r evi e wi n g I R B/ E C. M e dtr o nic will, as s o o n as p ossi bl e, pr o vi d e a writt e n st at e m e nt 
t o t h e i n v esti g at ors t o e n a bl e pr o m pt n otific ati o n of t h e I R B/ E C. If st u dy e nr oll m e nt is t er mi n at e d e arl y, 
f oll o w-u p visits will c o nti n u e f or all e nr oll e d s u bj ects.  
 
1 4. 1 1.  
S u s p e n si o n or E arl y T er mi n ati o n of a St u d y  Sit e  
M e dtr o nic m ay d eci d e  t o s us p e n d or pr e m at ur el y t er mi n at e a st u dy sit e ( e. g. i n c as e of ex piri n g 
a p pr o v al of t h e r e vi e wi n g I R B/ E C, n o n -c o m pli a nc e t o t h e CI P, or l ac k of e nr oll m e nt). If a st u dy sit e is 
s us p e n d e d or pr e m at ur ely t er mi n at e d, M e dtr o nic s h all pr o m ptl y i nf or m t h e i n v esti g at or(s) of t h e 
t er mi n ati o n or s us p e nsi o n a n d t h e r e as o n(s) f or t his. T h e i nv esti g at or s h all t h e n pr o m ptly i nf or m t h e 
r e vi e wi n g I R B/ E C. 
 
 
1 5. 1.  R e s p o n si biliti e s of t h e  I n v e sti g at or  
T h e i nv esti gat or is r es p o nsi bl e f or t h e pr e p ar ati o n, r evi e w, a n d si g n at ur e ( as a p plic a bl e), a n d r et e nti o n 
of t h e f oll o wi n g r ec or ds:  
•  
All ess e nti al c orr es p o n d e nc e t h at p ert ai ns t o t h e  i nv esti g ati o n 
•  
D evic e us e/ dis p ositi o n  r ec or ds 
•  
R ec or ds of e ac h s u bj ect’s c as e hist or y a nd ex p os ur e t o t h e d evic e. C as e hist ori es i ncl u d e t h e 
e C R Fs a n d s u p p orti n g d at a (s o urc e d oc u m e nt ati o n), i ncl u di n g, f or  ex a m pl e:  
•  
Si g n e d a n d d at e d c o ns e nt  f or ms 
•  
M e dic al r ec or ds, i ncl u di n g, f or ex a m pl e, pr o gr ess n ot es of t h e p hysici a ns , t h e s u bj ect’s h os pit al 
c h art(s) a n d t h e n urs es’ n ot es  
•  
All a dv ers e ev e nt/ d evic e d efici e ncy  i nf or m ati o n 
•  
A r ec or d of t h e ex p os ur e of e ac h s u bj ect t o t h e i nv esti g ati o n al d evic e ( e. g., d at e of i m pl a nt 
pr oc e d ur e a n d f oll o w -u p ass ess m e nt  d at es)  
•  
D oc u m e nt ati o n of  a ny d e vi ati o n fr o m t h e C I P, i ncl u di n g t h e d at e a n d t h e r ati o n al e f or s uc h 
d e vi ati o n  
•  
Si g n e d I nv esti g at or A gr e e m e nt, si g n e d a n d d at e d c urric ul u m vit a e of t h e PI, s u b -i nv esti g at or(s) 
a n d k e y m e m b ers, si g n e d D el e g at e d T as k  List 
•  
I n C a n a d a, I nv esti g at or’s A gr e em e nt i n acc or d a nc e wit h S u bs ecti o n 8 1( k) of t h e M e dic al D evic es 
R e g ul ati o ns  
1 5.  R e c or d R et e nti o n a n d R e p orti n g R e s p o n si biliti e s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 5 7  of 1 2 1  
 
 
All d e vi ati o ns, r e g ar dl ess of t h e r e as o n, s h all b e 
s u b mitt e d t o t h e s p o ns or. ( M HL W Or di n a nc e 3 6, 
2 0 0 5 Articl e 6 6)  
 
S u m m ary of t h e 
Cli nic al St u dy 
St at us  
 
 
H e a d of M e dic al 
I nstit uti o n 
T h e pri nci p al i nv esti g at or s h all s u b mit a s u m m ary of  
t h e cli nic al st u dy st at us t o t h e H e a d of M e dic al 
I nstit uti o n i n writi n g o nc e a y e ar, or m or e fr e q u e ntl y if 
r e q u est e d by t h e I R B/ E C, t o r ec eiv e t h e c o nti n u ati o n 
r e vi e w by t h e I R B/ E C. ( M HL W Or di n a nc e 3 6, 20 0 5 
Articl e 6 8)  
 
Pr e m at ur e 
T er mi n ati o n  
or S us p e nsi o n of t h e 
Cli nic al I nv esti g ati o n  
 
 
H e a d of M e dic al 
I nstit uti o n 
W h e n t h e pri nci p al i nv esti g at or disc o nti n u es or 
s us p e n ds t h e cli nic al st u dy, h e or s h e s h all pr o m ptly 
n otif y t h e H e a d of M e dic al I nstit uti o n t h er e of i n 
writi n g, a n d ex pl ai n i n d et ail i n writi n g t h e 
disc o nti n u ati o n or s us p e nsi o n. ( M HL W Or di n a nc e 
3 6, 2 0 0 5 Ar ticl e 6 9) 
 
C o m pl eti o n of t h e 
Cli nic al 
I nv esti g ati o n 
 
H e a d of M e dic al 
I nstit uti o n 
W h e n t h e cli nic al st u dy is c o m pl et e d, t h e pri nci p al 
i nv esti g at or s h all n otify t h e H e a d of M e dic al 
I nstit uti o n t her e of i n writi n g a n d r e p ort o n a 
s u m m ar y of t h e cli nic al st u dy r es ults i n writi n g. 
( M HL W Or di n a nc e 3 6, 2 0 0 5 Articl e 6 9) 
1 5. 2.  R e s p o n si biliti e s of t h e  S p o n s or  
T h e S p o ns or will m ai nt ai n t h e f oll o wi n g r ec or ds, i ncl u di n g b ut n ot li mit e d t o:  
•  
All ess e nti al c orr es p o n d e nc e r el at e d t o t h e cli nic al  st u dy 
•  
Si g n e d I nv esti g at or  A gr e e m e nt  
•  
Si g n e d a n d d at e d c urr e nt c urric ul u m vit a e f or e ac h  i nv esti g at or 
•  
R ec or ds of d evic e s hi p m e nt a n d dis p ositi o n (s hi p pi n g r ec ei pts, m at eri al d estr uct r ec or ds,  etc.)  
•  
A dv ers e ev e nt a n d d e vic e d efi ci e nc y i nf or m ati o n 
•  
All d at a f or ms, pr e p ar e d a n d si g n e d b y t h e i nv esti g at ors, a n d r ec ei v e d s o urc e d oc u m e nt ati o n 
a n d c or e l a b  r e p orts 
•  
CI P, i nv esti g at or br oc h ur e or r e p ort of pri or i nv esti g ati o ns a n d s u bs e q u e nt  a m e n d m e nts  
•  
Sit e m o nit ori n g  r e p orts 
•  
Fi n a nci al dis cl os ur e i nf or m ati o n 
•  
St u dy tr ai ni n g r ec or ds f or sit e p artici p a nts a n d i nt er n al st u dy st aff  m e m b ers  
•  
C o nt act lists of all p artici p ati n g i n v esti g at ors/i nv esti g ati v e sit es, st u dy m o nit ors a n d S p o ns or 
st aff m e m b ers; S p o ns or will m ai nt ai n t h es e lists a n d pr o vi d e u p d at es t o t h e n ec ess ar y  p arti es  
•  
S a m pl e of d evic e l a b eli n g att ac h e d t o i nv esti g ati o n al  d e vic e  
•  
I ns ur a nc e c ertific at es 
•  
Et hics B o ar d a p pr ov al d oc u m e nt ati o n a n d v oti n g  list 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 1  of 1 2 1  
 
 
 
 
 
h e a ds of all t h e m e dic al i nstit uti o ns ot h er f aciliti es 
e n g a g e d i n t h e cli nic al tri al t h er e of a n d t h e 
d et ail e d r e as o n t h er ef or i n writi n g. ( M HL W 
Or di n a nc e 3 6, 2 0 0 5 Articl e 3 2 ) 
 
 
 
 
 
 
I nv esti g at or List 
 
 
 
 
 
H e a d of M e dic al 
I nstit uti o n 
P M D A  
T h e s p o ns or s h all b ef or e h a n d s u b mit t h e list of 
i nv esti g at ors t o P M D A a n d H e a d of M e dic al 
I nstit uti o n. ( M HL W Or di n a nc e 3 6, 2 0 0 5 Articl e 1 0, 
P h ar m ac e utic al a n d M e dic al D evic e Act E nf orc e m e nt 
R e g ul ati o ns, Articl e 2 6 9, 2 7 5)  
 
T h e s p o ns or s h all s u b mit t h e list of i nv esti g at ors t o 
P M D A a n d H e a d of M e dic al I nstit uti o n w h e n 
m a ki n g a ny c h a n g es i n t h e list. ( M HL W Or di n a nc e 
3 6, 2 0 0 5 Articl e 5 1, P h ar m ac e utic al a n d M e dic al 
D evic e Act E nf orc e m e nt R e g ul a ti o ns, Articl e 2 7 0, 
2 7 5)  
 
 
W h e n n e w, i m p ort a nt i nf or m ati o n is o bt ai n e d, t h e 
I m p ort a nt i nf or m ati o n 
c o nc er ni n g t h e q u alit y, 
effic ac y, a n d s af et y of t h e 
i nv esti g ati o n al d evic e 
Pri nci p al  
I nv esti g at or 
H e a d of M e dic al 
I nstit uti o n 
P M D A  
s p o ns or s h all r evis e t h e i nv esti g at or’s br oc h ur e. I n 
a d diti o n, pri or t o r evisi n g t h e i nv esti g at or’s br oc h ur e, 
t h e s p o ns or s h all r e p ort t h e i nf or m ati o n t o t h e 
pri nci p al i nv esti g at or, H e a d of M e dic al I nstit uti o n, 
a n d r e g ul at ory a ut h oriti es.  ( M HL W Or di n a nc e 3 6, 
 
 
2 0 0 5 Articl e 2 8)  
 
 
Cli nic al Tri al R e p ort  
 
P M D A  
u p o n r e q u est  
T h e s p o ns or s h all pr e p ar e, acc or di n g t o t h e 
pr oc e d ur e, a cli nic al st u dy r e p ort t h at s u m m ariz es 
t h e r es ults, etc., of a cli nic al st u dy w h e n it is 
c o m pl et e d or disc o nti n u e d. ( M HL W Or di n a nc e 3 6, 
Articl e 3 3)  
 
 
E ns ur e  t h at all d evi ati o ns fr o m t h e CI P ar e r e vi ew e d  
 
 
wit h t h e a p pr o pri at e cli nic al i nv esti g at or(s), ar e  
 
 
r e p ort e d o n t h e c as e r e p ort f or ms a n d t h e fi n al 
 
Pri nci p al  
r e p ort of t h e cli nic al i n v esti g ati o n.  (IS O 1 4 1 5 5: 2 0 1 1) 
 
St u dy d e vi ati o n  
I nv esti g at or 
H e a d of M e dic al 
I nstit uti o n 
as n ec ess ar y  
W h e n t h e m o nit or c o nfir ms d e vi ati o n as a r es ult of 
m o nit ori n g, t h e m o nit or s h all n otify t h e pri nci p al 
i nv esti g at or a n d, as n ec ess ar y, t h e H e a d of M e dic al 
I nstit uti o n t h er e of.  T h e m o nit or s h all als o r e q u est 
 
 
f or a p pr o pri at e m e as ur es t o b e t a k e n t o pr ev e nt 
 
 
s uc h d e vi ati o n i n t h e f ut ur e.  ( M HL W Or di n a nc e 3 6, 
 
 
2 0 0 5 Articl e 3 0)  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 2  of 1 2 1  
 
 
 
1 5. 3.  R e c or d  R et e nti o n  
T h e i nv esti g at or m ust r et ai n t h e I nv esti g at or Sit e Fil e, s o urc e d oc u m e nts, a n d t h e r ec or ds list e d i n 
S ecti o n 1 5. 1 . R es p o nsi biliti es of t h e I n v esti g at or , u ntil i nf or m e d b y M e dtr o nic t h e y n o l o n g er n e e d t o 
b e r et ai n e d. At a mi ni m u m, t h e i nv esti g at or m ust r et ai n r ec or ds f or at l e ast 3 y e ars ( or l o n g er if r e q uir e d 
by l oc al l a w) aft er t h e l ast a p pr o v a l of a m ar k eti n g a p plic ati o n a n d u ntil t h er e ar e n o p e n di n g or 
c o nt e m pl at e d m ar k eti n g a p plic ati o ns, or at l e ast 3 y e ars h a v e el a ps e d si nc e t h e f or m al disc o nti n u ati o n 
of t h e cli nic al st u dy or cli nic al d e v el o p m e nt of t h e i n v esti g ati o n al d evic es. T h e i nv esti g at or s h o ul d t a k e 
m e as ur es t o pr e v e nt acci d e nt al or e arly d estr ucti o n of t h e st u dy r el at e d  m at eri als.  
 
M e dtr o nic will m ai nt ai n st u dy r ec or ds u n d er its r es p o nsi bilit y i n acc or d a nc e wit h f e d er al l a ws a n d 
r e g ul ati o ns, J-G C P a n d M e dtr o nic p olic y.  
 
 
1.  
T h erri e n  J, Pr o v ost  Y,  M erc h a nt  N,  Willi a ms  W,  C ol m a n  J, W e b b  G.  O pti m al  ti mi n g f or p ul m o n ary 
v al v e r e pl ac e m e nt i n a d ults aft er t etr al o gy of F all ot r e p air. T h e A m eric a n j o ur n al of c ar di ol o gy 
2 0 0 5; 9 5: 7 7 9 -8 2.  
2.  
L ucr o n H, M arc o n F, B oss er G, L et h or J P, M ari e P Y, Br e m bill a -P err ot B. I n d ucti o n of s ust ai n e d 
v e ntric ul ar t ac hyc ar di a aft er s ur gic al r e p air of t etr al o gy of F all ot. T h e A m eric a n j o ur n al of c ar di ol o gy 
1 9 9 9; 8 3: 1 3 6 9 -7 3.  
3.  
H or n eff er PJ, Z a h k a K G, R o w e S A, et al. L o n g -t er m r es ults of t ot al r e p air of t etr al o gy of F all ot i n 
c hil d h o o d. T h e A n n als of t h or acic s ur g er y 1 9 9 0; 5 0: 1 7 9 -8 3; disc ussi o n  8 3 -5.  
4.  
G atz o ulis  M A, B al aji S, W e b b er S A, et al. Risk f act ors f or arr hyt h mi a a n d s u d d e n c ar di ac d e at h 
l at e aft er r e p air of t etr al o gy of F all ot: a m ultic e ntr e st u dy. L a nc et 2 0 0 0; 3 5 6: 9 7 5 -8 1.  
5.  
R ot h m a n A, P erry S B, K e a n e J F, L oc k J E. E arly r es ults a n d f oll o w -u p of b all o o n a n gi o pl ast y f or 
br a nc h  p ul m o n ar y  art ery  st e n os es. J o ur n al of  t h e A m eric a n  C oll e g e  of  C ar di ol o gy  1 9 9 0; 1 5: 1 1 0 9 -1 7.  
6.  
K a v ey R E, T h o m as F D, Byr u m CJ, Bl ac k m a n M S, S o n d h ei m er H M, B o v e  EL. V e ntric ul ar 
arr hyt h mi as a n d bi v e ntric ul ar d ysf u ncti o n aft er r e p air of t etr al o gy  of F all ot. J o ur n al of t h e A m eric a n 
C oll e g e of C ar di ol o gy  1 9 8 4; 4: 1 2 6 -3 1.  
7.  
B o v e  EL,  B yr u m  CJ,  T h o m as  F D,  et  al.  T h e  i nfl u e nc e of  p ul m o n ary  i ns uffici e nc y o n  v e ntric ul ar 
f u nctio n f oll o wi n g r e p air of t etr al o gy of F all ot. E v al u ati o n usi n g r a di o n ucli d e v e ntric ul o gr a p hy. T h e 
J o ur n al of t h or acic a n d c ar di o v asc ul ar s ur g ery 1 9 8 3; 8 5: 6 9 1 -6.  
8.  
G atz o ulis M A, Till J A, S o m er vill e J, R e di n gt o n A N. M ec h a n o el ectric al i nt er acti o n i n t etr al o gy of 
F all ot. Q R S pr ol o n g ati o n r el at es t o ri g ht v e ntric ul ar siz e a n d pr e dicts m ali g n a nt v e n tric ul ar arr hyt h mi as 
a n d s u d d e n d e at h. Circ ul ati o n  1 9 9 5; 9 2: 2 3 1 -7.  
9.  
C ar v al h o J S, S hi n e b o ur n e E A, B usst  C, Ri g by ML, R e di n gt o n A N. Ex ercis e c a p acit y aft er c o m pl et e 
r e p air of tetr al o gy of F all ot: d el et eri o us eff ects of r esi d u al p ul m o n ar y r e g ur git ati o n. Britis h h e art j o ur n al 
1 9 9 2; 6 7: 4 7 0 -3.  
1 0.  
T h erri e n J, Si u S C, H arris L, et al. I m p act of p ul m o n ar y v al v e r e pl ac e m e nt o n arr hyt h mi a 
pr o p e nsit y  l at e aft er  r e p air of  t etr al o gy of  F all ot.  Circ ul ati o n  2 0 0 1; 1 0 3: 2 4 8 9 -9 4.  
1 1.  
E ys k e ns B, R ey br o uc k  T, B o g a ert J, et al. H o m o gr aft i ns erti o n f or p ul m o n ar y r e g ur git ati o n aft er 
r e p air of t etr al o gy of f all ot i m pr ov es c ar di or es pir at or y ex ercis e p erf or m a nc e. T h e A m eric a n j o ur n al of 
c ar di ol o gy 2 0 0 0; 8 5: 2 2 1 -5.  
1 6.  R ef er e n c e s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 3  of 1 2 1  
1 2.  
K a nt er K R, B u d d e J M, P ar ks WJ, et al . O n e h u n dr e d p ul m o n ary v al v e r e pl ac e m e nts i n c hil dr e n 
aft er r eli ef of ri g ht v e ntric ul ar o utfl o w tr act o bstr ucti o n. T h e A n n als of t h or acic s ur g er y 2 0 0 2; 7 3: 1 8 0 1 -6; 
disc ussi o n  6 -7.  
1 3.  
Bi el ef el d M R, Bis h o p D A, C a m p b ell D N, Mi tc h ell M B, Gr o v er FL, Cl ar k e D R. R e o per ati v e 
h o m o gr aft ri g ht v e ntric ul ar o utfl o w tr act r ec o nstr ucti o n. T h e A n n als of t h or acic s ur g er y 2 0 0 1; 7 1: 4 8 2 -7; 
disc ussi o n  7 -8.  
1 4.  
C h e at h a m J P, H ell e n br a n d W E, Z a h n E M, et al. Cli nic al a n d H e m o dy n a mic O utc o m es U p t o 7 
Y e ar s Aft er Tr a nsc at h et er P ul m o n ary V alv e R e pl ac e m e nt i n t h e U S M el o dy V al v e I nv esti g ati o n al D evic e 
Ex e m pti o n Tri al. Circ ul ati o n  2 0 1 5.  
1 5.  
Sc hi e v a n o S, C o ats L, Mi gli av acc a F, et al. V ari ati o ns i n ri g ht v e ntric ul ar o utfl o w tr act 
m or p h ol o gy f oll o wi n g r e p air of c o n g e nit al h e art dis e as e: i m plic ati o ns f o r p erc ut a n e o us p ul m o n ary v al v e 
i m pl a nt ati o n. J o ur n al of c ar di o v asc ul ar m a g n etic r es o n a nc e : offici al j o ur n al of t h e S oci ety f or 
C ar di o v asc ul ar M a g n etic R es o n a nc e  2 0 0 7; 9: 6 8 7 -9 5.  
1 6.  
d e R uijt er F T, W e e ni n k I, Hitc hc ock J F, B e n ni nk G B, M eij b o o m EJ. Ri g ht v e ntric u l ar d ysf u ncti o n 
a n d t h e r ol e of p ul m o n ary v al v e r e pl ac e m e nt aft er c orr ecti o n of t etr al o gy of F all ot. N et h erl a n ds h e art 
j o ur n al : m o nt hl y j o ur n al of t h e N et h erl a n ds S oci ety of C ar di ol o gy a n d t h e N et h erl a n ds H e art 
F o u n d at i o n 2 0 0 1; 9: 2 6 9 -7 4.  
1 7.  
Disci gil B, D e ar a n i J A, P u g a FJ, et al. L at e p ul m o n ar y v al v e r e pl ac e m e nt aft er r e p air of t etr al o gy 
of F all ot. T h e J o ur n al of t h or acic a n d c ar di o v asc ul ar s ur g er y  2 0 0 1; 1 2 1: 3 4 4 -5 1.  
1 8.  
B o v e EL, K a v e y R E, Byr u m CJ, S o n d h ei m er  H M, Bl ack m a n M S, T h o m as F D. I m pr o v e d ri g ht 
v e ntric ul ar f u ncti o n f oll o wi n g l at e p ul m o n ar y v alv e r e pl ac e m e nt f or r esi d u al p ul m o n ary i ns uffici e nc y or 
st e n osis. T h e J o ur n al of t h or acic a n d c ar di o v asc ul ar s ur g er y 1 9 8 5; 9 0: 5 0 -5.  
1 9.  
B o u dj e mli n e Y, A g n ol etti G, B o n n e t D, Si di D, B o n h o eff er P. P erc ut a n e o us p ul m o n ar y v al v e 
r e pl ac e m e nt i n a l ar g e ri g ht v e ntric ul ar o utfl o w tr act: a n ex p eri m e nt al st u dy. J o ur n al of t h e A m eric a n 
C oll e g e of C ar di ol o gy  2 0 0 4; 4 3: 1 0 8 2 -7.  
2 0.  
B o u dj e mli n e Y, Sc hi ev a n o S, B o n n et C, et al. Off -p u m p r e pl a c e m e nt of t h e p ul m o nar y v al v e i n 
l ar g e ri g ht v e ntric ul ar o utfl o w tr acts: a h y bri d a p pr o ac h. T h e J o ur n al of t h or acic a n d c ar di o v asc ul ar 
s ur g er y 2 0 0 5; 1 2 9: 8 3 1 -7.  
2 1.  
Dittric h S, Gl o ec kl er  M, Ar n ol d R, et al. Hy bri d p ul m o n ar y v alv e i m pl a nt ati o n: i nj ecti o n of a s elf - 
ex p a n di n g tiss u e v alv e t hr o u g h t h e m ai n p ul m o n ar y art er y. T h e A n n als of t h or acic s ur g er y 2 0 0 8; 8 5: 6 3 2 - 
4.  
2 2.  
Sc hr ei b er C, H or er J, V o gt M, et al. A n e w tr e at m e nt o pti o n f or p ul m o n ar y v alv ar i ns uffici e nc y: 
first ex p eri e nc es wit h i m pl a nt ati o n of a s elf-ex p a n di n g st e nt e d v alv e wi t h o ut us e of c ar di o p ul m o n ary 
by p ass. E ur o p e a n j o ur n al of c ar di o -t h or acic s ur g er y : offici al j o ur n al of t h e E ur o p e a n Ass oci ati o n f or 
C ar di o -t h or acic S ur g ery 2 0 0 7 ; 3 1: 2 6-3 0.  
2 3.  
Bi er n ac k a E K, R uzyłł o W, D e m k o w M, et al. Tr a nsc at h et er p ul m o n ary v al v e i m pl a nt ati o n i n 
p ati e nts wit h ri g ht v e ntric ul ar o utfl o w tr act d ysf u ncti o n: E arly a n d mi d -t er m r es ults. J o ur n al of I nv asi v e 
C ar di ol o gy  2 0 1 5; 2 7: E 8 2 -E 9.  
2 4.  
M e a d o ws JJ, M o or e P M, B er m a n D P, et al. Us e a n d P erf or m a nc e of t h e M el o dy Tr a nsc at h et er 
P ul m o n ar y V al v e i n N ativ e a n d P osts ur gic al, N o nc o n d uit Ri g ht V e ntric ul ar O utfl o w Tr acts. Circ ul ati o n 
C ar di o v asc ul ar i nt erv e nti o ns  2 0 1 4.  
2 5.  
M al e kz a d e h -Mil a ni S, L a d o uc e ur M, C o h e n S, Is eri n L, B o u dj e mli n e Y. R es ults of tr a nsc at h et er 
p ul m o n ary v alv ul ati o n i n n ati v e or p atc h e d ri g ht v e ntric ul ar o utfl o w tr acts. Arc hiv es of c ar di ov asc ul ar 
dis e as es  2 0 1 4; 1 0 7: 5 9 2 -8.  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 4  of 1 2 1  
 
 
 
2 6.  
P hilli ps A B, N evi n P, S h a h A,  Ols h ov e V, G ar g R, Z a h n E M. D e v el o p m e nt of a n o v el h y bri d 
str at e gy f or tr a nsc at h et er p ul m o n ary v alv e pl ac e m e nt i n p ati e nts f oll o wi n g tr a ns a n n ul ar p atc h r e p air of 
t etr al o gy of f all ot. C at h et eriz ati o n a n d c ar di o v asc ul ar i nt er v e nti o ns : offici al j o ur n al of th e S oci ety f or 
C ar di ac A n gi o gr a p hy & I nt er v e nti o ns  2 0 1 6; 8 7: 4 0 3 -1 0.  
2 7.  
Pr o m p h a n W, Pr ac h asilc h ai P, Siri p or n pit a k S, Q ur es hi S A, L a y a n g o ol T. P erc ut a n e o us p ul m o n ar y 
v al v e i m pl a nt ati o n wit h t h e V e n us P -v alv e: cli nic al ex p eri e nc e a n d e arl y r es ults. C ar di ol o gy i n  t h e y o u n g 
2 0 1 6; 2 6: 6 9 8 -7 1 0.  
2 8.  
C a o QL, K e n ny D, Z h o u D, et al. E arly cli nic al ex p eri e nc e wit h a n ov el s elf -ex p a n di n g 
p erc ut a n e o us st e nt -v alv e i n t h e n ativ e r i g ht v e ntric ul ar o utfl o w tr act. C at h et eriz ati o n a n d c ar di ov asc ul ar 
i nt er v e nti o ns : offici al  j o ur n al of  t h e S oci et y  f or C ar di ac  A n gi o gr a p hy  &  I nt erv e nti o ns 2 0 1 4; 8 4: 1 1 3 1 -7.  
2 9.  
B os h off D E, C o ols BL M, H eyi n g R, et al. Off -l a b el us e of p erc ut a n e o us p ul m o n ary v al v ed st e nts i n 
t h e ri g ht v e ntric ul ar o utfl o w tr act: Ti m e t o r e writ e t h e l a b el ? C at h et eriz ati o n a n d C ar di ov asc ul ar 
I nt er v e nti o ns 2 0 1 3; 8 1: 9 8 7 -9 5.  
3 0.  
D e m k o w M, R uzyłł o W, Bi er n ac k a E K, et al. P erc ut a n e o us e d w ar ds S A PI E N T M v alv e i m pl a nt ati o n 
f or si g nific a nt p ul m o n ary r e g ur git ati o n aft er pr e vi o us s ur gic al r e p air wit h a ri g ht v e ntric ul ar o utfl o w 
p atc h. C at h et eriz ati o n  a n d C ar di o v asc ul ar I nt erv e nti o ns  2 0 1 4; 8 3: 4 7 4 -8 1.  
3 1.  
H a as N A, M o ysic h A, N e u d orf U, et al. P erc ut a n e o us i m pl a nt ati o n of t h e E d w ar ds S A PI E N ™ 
p ul m o nic  v alv e:  I niti al r es ults i n t h e first 2 2  p ati e nts.  Cli nic al  R es e arc h  i n C ar di ol o gy  2 0 1 3; 1 0 2: 1 1 9 -2 8.  
3 2.  
“ E d w ar ds S A PI E N P ul m o nic Tr a nsc at h er H e art V alv e.” [ O nli n e]. Av ail a bl e: 
htt p:// w w w. e d w ar ds.c o m/ e u/ pr o d ucts/tr a nsc at h et erv al v es/ P a g es/ p ul m o nic. as px . [ Acc ess e d: 1 8-J ul- 
2 0 1 6].  
3 3.  
Sc hi e v a n o S, T ayl or A M, C a p elli C, et a l. First-i n-m a n i m pl a nt ati o n of a n o v el p erc ut a n e o us v alv e: 
a n e w a p pr o ac h t o m e dic al d e vic e d ev el o p m e nt. E ur oI nt er v e nti o n : j o ur n al of E ur o P C R i n c oll a b or ati o n 
wit h t h e W or ki n g Gr o u p o n I nt er v e nti o n al C ar di ol o gy of t h e E ur o p e a n S oci ety of C ar di ol o gy 2 0 1 0; 5: 7 4 5 - 
5 0.  
3 4.  
B er g ers e n L, B e ns o n L N, Gill es pi e MJ, et al. H ar m o ny F e asi bilit y Tri al: Ac ut e a n d S h ort -T er m 
O utc o m es  Wit h  a  S elf -Ex p a n di n g  Tr a nsc at h et er  P ul m o n ar y  V alv e.  J A C C C ar di o v asc ul ar  i nt er v e nti o ns 
2 0 1 7; 1 0: 1 7 6 3 -7 3.  
3 5.  
Nis hi m ur a R A, Ott o C M, B o n o w R O, et al.  2 0 1 4 A H A/ A C C g ui d eli n e f or t h e m a n a g e m e nt of 
p ati e nts  wit h  v alv ul ar  h e art  dis e as e:  a  r e p ort of  t h e A m eric a n  C oll e g e  of  C ar di ol o gy/ A m eric a n  H e art 
Ass oci ati o n T as k F orc e o n Pr actic e G ui d eli n es. J o ur n al of t h e A m eric a n C oll e g e of C ar di ol o gy 
2 0 1 4; 6 3: e 5 7 -1 8 5.  
3 6.  
“I nt er n ati o n al St a n d ar d I S O 1 4 1 5 5: 2 0 1 1( E). Cli nic al i nv esti g ati o n of m e dic al d evic es f or h u m a n 
s u bj ects - G o o d Cli nic al  Pr actic e.”.  
3 7.  
“ M E D D E V 2. 7/ 3 r evisi o n 3 M a y 2 0 1 5: G ui dli n es  o n m e dic al d e vic es; Cli nic al i n v esti g ati o ns: 
s eri o us a dv ers e e v e nt r e p orti n g u nd er dir ectiv es 9 0/ 3 8 5/ E E C a n d  9 3/ 4 2/ E E C.”  
3 8.  
“ U nit e d St at es F o o d a n d Dr u g A d mi nistr ati o n C o F R, 2 1 C F R P art 8 1 2. 3 (s).”  . 
3 9.  
Gill es pi e MJ, B e ns o n L N, B er g ers e n L, et al. P ati e nt S el ec ti o n Pr oc ess f or t h e H ar m o ny 
Tr a nsc at h et er  P ul m o n ary  V al v e  E arl y  F e asi bilit y  St u dy.  T h e  A m eric a n  j o ur n al of  c ar di ol o gy 2 0 1 7.  
 
 
A p p e n dix I: I nf or m e d C o ns e nt T e m pl at e 
A p p e n dix II: A dv ers e E v e nt D efi niti o ns  
1 7.  A p p e n di c e s  

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 6  of 1 2 1  
 
 
 
4. 0  
•  
A d diti o n of J a p a n  g e o gr a p h y  
•  
Ex p a n d e d sc o p e of d oc u m e nt t o i ncl u d e 
J a p a n r e g ul at or y r e q uir e m e nts 
•  
A dj ust m e nt of pr e -i m pl a nt wi n d o w f or 
i m a gi n g r e q uir e m e nts 
•  
A d diti o n of p ost -c ar e lif el o n g As piri n a n d 
pr o p h yl actic a nti bi otic t h er a py 
r ec o m m e n d ati o n 
•  
A d diti o n of s ecti o n r e g ar di n g r ol e & 
m e m b ers hi p of scr e e ni n g  c o m mitt e e 
•  
R evis e d A p p e n dix VII A n at o mic C ar di ac 
M a g n etic R es o n a nc e I m a gi n g Pr ot oc ol t o 
b ec o m e a S u b -st u d y i ncl u di n g s u bs e q u e nt 
r e q uir e m e nts 
•  
R e m o v e d r e q uir e m e nt f or sit es t o  p erf or m 
a n at o mic m e as ur e m e nts o n C T  a n d M RI 
i m a g es 
•  
Mi n or a d mi nistr ati v e c h a n g es  t hr o u g h o ut 
N ot e: V ersi o n 4. 0 of t his d oc u m e nt m a y n ot ali g n t o t h e 
v ersi o n of t h e d oc u m e nt d et er mi n e d i n t h e M e dtr o nic 
Tri al M ast er Fil e ( R A D)  
 
 
 
 
5. 0  
•  
A d d e d i nf or m ati o n d escri bi n g a d diti o n al 
siz e H ar m o n y T P V d evic e  
•  
A d diti o n of s ecti o n d escri bi n g a s u bs et of 
s u bj ects f or i niti al i m pl a nt of t h e H ar m o n y 
T P V  2 5  
•  
A d diti o n of a p ost -i m pl a nt C T s u b-st u dy 
A p p e n dix  XIII  
•  
A dj ust m e nt of pr e -i m pl a nt wi n d o w f or 
i m a gi n g r e q uir e m e nts 
•  
Mi n or a d mi nistr ati v e c h a n g es  t hr o u g h o ut 
 
 
6. 0  
•  
A d d e d i nf or m ati o n d escri bi n g a d diti o n al 
m o difi e d T P V 2 5 siz e H ar m o n y T P V  d evic e  
•  
R e m o v e d l a n g u a g e all o wi n g d ef erri n g 
s u bj ects 
•  
A d d e d disc h ar g e C T a n d o n e m o nt h p ost - 
i m pl a nt f u ncti o n al C M R f or m T P V 2 5 
i m pl a nts 
•  
R e m o v e d scr e e ni n g l o g  r e q uir e m e nts 
•  
U p d at e d A p p e n dix XII f or P ost I m pl a nt C T 
S u b -st u d y 
•  
Mi n or a d mi nistr ati v e c h a n g es  t hr o u g h o ut 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 7  of 1 2 1  
 
 
 
A p p e n di x I: I N F O R M E D C O N S E N T  T E M P L A T E  
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5,  v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 8  of 1 2 1  
 
 
 
 
A p p e n di x I I: A D V E R S E E V E N T  D E F I N I T I O N S  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 6 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g at i o n Pl a n 
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g at i o n Pl a n 
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 2  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 3  of 1 2 1  
 
 
 
A p p e n di x I I I: A D V E R S E E V E N T C O D E  L I S T  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
    
 
 
 
 
 
 
 
     
 
     
 
 
 
 
     
 
 
 
 
 
 
 
 
 
      
 
      
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 7  of 1 2 1  
 
 
 
A p p e n di x I V: E C H O C A R D I O G R A P H Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
      
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 9  of 1 2 1  
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 0 of 1 2 1  
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 4. 2.  
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 2  of 1 2 1  
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 3  of 1 2 1  
 
 
 
 
4. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 4  of 1 2 1  
 
 
 
A p p e n di x V: R A D I O G R A P H Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 5  of 1 2 1  
 
 
4. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
 
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 6  of 1 2 1  
 
 
 
A p p e n di x V I: C A R D I A C M A G N E T I C R E S O N A N C E I M A G I N G 
P R O T O C O L -F U N C T I O N A L  P A R A M E T E R S  
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
      
 
 
 
      
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 7  of 1 2 1  
M
l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 9 0 of 1 2 1  
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 1  of 1 2 1  
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 2  of 1 2 1  
 
 
 
      
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 3  of 1 2 1  
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 4  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 5  of 1 2 1  
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 6  of 1 2 1  
 
 
 
    
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 7  of 1 2 1  
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 8  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 9  of 1 2 1  
 
 
 
    
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 2  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 3  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
A p p e n di x V I I: C O M P U T E D T O M O G R A P H I C A N G I O G R A P H Y ( C T ) 
I M A G I N G  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
•  
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
•  
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
3. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. 0  
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 7  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 1 0 8  of 1 2 1  
 
 
 
A p p e n di x V I I I: A N A T O M I C M E A S U R E M E N T S A N D D E V I C E S I Z I N G 
G U I D E L I N E S  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n P l a n T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 1 0 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 1 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 1 1 of 1 2 1  
 
 
 
A p p e n di x I X: E X P L A N T  P R O T O C O L  
 
 
 
 
1. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 2  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
A p p e n di x X: I N S T R U C T I O N S F O R U S E  D O C U M E N T  
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 3  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
A p p e n di x X I: S F -3 6  Q U E S T I O N N A I R E  
 
 
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 7  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
A p p e n di x X I I: P O S T -I M P L A N T C O M P U T E D T O M O G R A P H I C 
A N G I O G R A P H Y ( C T A ) I M A G I N G S U B -S T U D Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 2 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 2 1 of 1 2 1  
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
      
 
 
 
 
 
      
 
 
 
 
 
 
5. 0  
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g at i o n Pl a n 
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g at i o n Pl a n 
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 2  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 3  of 1 2 1  
A p p e n di x I I I: A D V E R S E E V E N T C O D E  L I S T  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
    
 
 
 
 
 
 
 
     
 
     
 
 
 
 
     
 
 
 
 
 
 
 
 
 
      
 
      
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 7  of 1 2 1  
 
 
 
A p p e n di x I V: E C H O C A R D I O G R A P H Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
      
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
     
     

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 7 9  of 1 2 1  
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 0 of 1 2 1  
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 4. 2.  
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 2  of 1 2 1  
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g a ti o n Pl a n T e m pl at e 
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 3  of 1 2 1  
 
 
 
 
4. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 4  of 1 2 1  
A p p e n di x V: R A D I O G R A P H Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 5  of 1 2 1  
 
 
4. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
 
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 6  of 1 2 1  
A p p e n di x V I: C A R D I A C M A G N E T I C R E S O N A N C E I M A G I N G 
P R O T O C O L -F U N C T I O N A L  P A R A M E T E R S  
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
      
 
 
      
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  
      
      

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 7  of 1 2 1  
M
l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 8 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
      
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 9 0 of 1 2 1  
      
 
 
 
 
 
 
 
 
 
 
 
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 1  of 1 2 1  
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 2  of 1 2 1  
 
 
 
      
 
 
 
 
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 3  of 1 2 1  
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 4  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 5  of 1 2 1  
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 6  of 1 2 1  
    
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 7  of 1 2 1  
    
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 8  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 9 9  of 1 2 1  
    
 
 
 
    
 
 
 
 
 
 
 
 
   

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 1  of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n  T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 2  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 3  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
A p p e n di x V I I: C O M P U T E D T O M O G R A P H I C A N G I O G R A P H Y ( C T ) 
I M A G I N G  P R O T O C O L  
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
      
 
 
 
 
 
 
      
 
 
 
 
 
     

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
•  
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
     

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
•  
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
3. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. 0  
 
 
 
     

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 0 7  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 1 0 8  of 1 2 1  
A p p e n di x V I I I: A N A T O M I C M E A S U R E M E N T S A N D D E V I C E S I Z I N G 
G U I D E L I N E S  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is  el e ctr o ni c all y  c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n P l a n T e m pl at e  

H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er s i o n  6. 0 
P a g e 1 0 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 1 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y ™ T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n  6. 0  
P a g e 1 1 1 of 1 2 1  
 
 
 
A p p e n di x I X: E X P L A N T  P R O T O C O L  
 
 
 
 
1. 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 2  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
A p p e n di x X: I N S T R U C T I O N S F O R U S E  D O C U M E N T  
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 3  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
A p p e n di x X I: S F -3 6  Q U E S T I O N N A I R E  
 
 
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 4  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 5  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 6  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 7  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 8  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
 
 

H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt  # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 1 9  of 1 2 1  
M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
 
 
 
A p p e n di x X I I: P O S T -I M P L A N T C O M P U T E D T O M O G R A P H I C 
A N G I O G R A P H Y ( C T A ) I M A G I N G S U B -S T U D Y  P R O T O C O L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 2 0 of 1 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
     

M e dtr o ni c C o nfi d e nti al  
T his d o c u m e nt is el e ctr o ni c all y c o ntr oll e d  
0 5 6 -F 2 7 5, v A Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
H ar m o n y T P V Cli ni c al I n v e sti g ati o n Pl a n  
D o c u m e nt # M D T 1 6 0 0 4 C O N 0 0 1  
V er si o n   6. 0  
P a g e 1 2 1 of 1 2 1  
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
      
 
 
 
 
 
      
 
 
 
 
 
 
5. 0