SAO PAULO
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C e s a r J o s e G r u p i, P a u lo J o r g e M o f f a , S f / v ia A lv e s B a r b o s a , P a u lo C e s a r S a n c h e s , E n iv a m G .B a r r a g a n F ilh o , G io v a n n i M . V .B e llo t t i, F u lv ia J o s e C a r lo s P ile g g i
H o lte r m o n ito rin g in C h a g a s' h e a rt d ise a se
Heart Institute, Hospital das Clinicas da Faculdade
de Medicina
da Universidade de sao Paulo - sao Paulo, Brazil
E le ctro ca rd io g ra p h ic ryth m d istu rb a n ce e va lu a tio n b y H o lte r m o n ito rin g is in cre a sin g ly b e co m in g a u se fu l m e th o d o lo g ic to o l fo r risk stra tifica tio n a s w e ll a s fo r th e ra p e u tic a sse ssm e n t in p a tie n ts w ith C h a g a s' d e se a se . F u rth e rm o re , la te p o te n tia l a n a lyse s, n o w
b e in g d ire ctly o b ta in e d fro m H o lte r re co rd in g h a s p ro m isin g p e rsp e ctive s in e n h a n cin g id e n tifica tio n o f p a tie n ts w ith h ig h risk p ro file s fo r d e ve lo p m e n t o f m a lig n a n t ve n tricu la r a rrh yth m ia s. In a d d itio n , re ce n tly in co rp o ra te d to H o lte r stu d ie s, h e a rt ra te va ria b ility a n a lysis w ill ce rta in ly co n trib u te to a b e tte r u n d e rsta n d in g o f th e ch a ra cte ristic a u to n o m ic n e rvo u s syste m d isa rra y th a t
co m m o n ly a ffe cts ch a g a sic p a tie n ts.
U N IT E R M S : C h a g a s d ise a se . H o lte r m o n ito rin g .
IN T R O D U C T IO N
T
h e p o s s ib ility o f c o n tin u o u s ly r e c o r d in g th e e le c tr o c a r d io g r a m ( E C G ) o v e r lo n g p e r io d s o f tim e a n d its s u b s e q u e n t r a p id a n a ly s is , c u r r e n tly u s in g a u to m a tic c o m p u te r iz e d p r o c e s s e s , w a s in tr o d u c e d to c lin ic a l p r a c tic e b y N o r m a n H o lte r in 1 9 6 1 ( 1 9 ) . T h isA d d r e s s f o r c o r r e s p o n d e n c e :
C e s a r J o s e G r u p i
D iv is B o d e M e t o d o s G r a f ic o s ( S e r v ir ; o d e H o lt e r ) I n s t it u t o d o C o r a r ; B o - H o s p it a l d a s C lf n ic a s d a F M U S P A v . D r . E n e a s d e C a r v a lh o A g u ia r , 4 4
S a o P a u lo - S P - B r a s il- C E P 0 5 4 0 3 - 0 0 0
in s tr u m e n ta l p r a c tic e a llo w e d n o r m a lly tr a n s ito r y e le c tr o c a r d io g r a p h ic a lte r a tio n s o f s p e c if ic p o p u la tio n s , c a r r ie r s o r n o t ( 4 ,3 0 ) o f d if f e r e n t c a r d io p a th ie s ( 6 ,4 0 ) , to b e r e c o g n iz e d a n d r e la te d to th e p r o g n o s is . I n th is w a y g r o u p s o f p a tie n ts w ith C h a g a s ' d is e a s e w e r e a ls o o b s e r v e d ( 2 7 ,3 8 ) .
I t is k n o w n th a t o n e o f th e p r in c ip a l lim ita tio n s o f th e c o n v e n tio n a l E C G is its s h o r t tim e o f o b s e r v a tio n . W ith H o lte r 's m e th o d , th e r e is a g r e a t in c r e a s e in th e c a p a c ity to d e te c t in te r m itte n t a lte r a tio n s , w ith a n o b s e r v a tio n o f 2 4 h o u r s s h o w in g th e b e s t c o s t/b e n e f it r a tio ( 3 ) . I ts u tility in C h a g a s ' d is e a s e w a s e v a lu a te d b y M a g u ir e ( 2 6 ) ( a m o n g o th e r s ) , w h e r e 8 0 % o f th e p a tie n ts th a t d e m o n s tr a te d a n o r m a l c o n v e n tio n a l E C G r e a d in g w e r e r e v e a le d to h a v e v e n tr ic u la r e x tr a s y s to le s , w ith a n a v e r a g e o f 1 /h o u r a n d 6 .7 % o f p a ir s o r v o lle y s in th e H o lte r m e th o d . I n th e c a s e
S a o P a u lo M e d ica l Jo u rn a l/R P M 1 1 3 (2 ) M a r/A p r 1 9 9 5
o f c o n v e n t i o n a l E C G w i t h v e n t r i c u l a r e x t r a s y s t o l e s , t h e i r p r e s e n c e w a s c o n f i r m e d w i t h t h e H o l t e r m e t h o d i n a l l p a t i e n t s , w i t h a d e n s i t y o f 2 9 0 / h o u r a n d 8 8 % o f t h e c a s e s w i t h p a i r s o r v o l l e y s . T h i s s a m e a u t h o r , c o m p a r i n g b e t w e e n t h e d i f f e r e n t e l e c t r o c a r d i o g r a p h i c m e t h o d s - c o n v e n t i o n a l E C G , e x e r c i s e E C G , a n d H o l t e r 's m e t h o d - , a l s o d e m o n s t r a t e d t h a t t h e l a t t e r w a s t h e o n l y o n e c a p a b l e o f i d e n t i f y i n g m o s t p a t i e n t s w i t h a r r h y t h m i a s , i n c l u d i n g t h o s e w i t h t h e m o s t s e v e r e f o r m s ( 2 7 ) .
I t s h o u l d b e r e m e m b e r e d t h a t t h i s m e t h o d g i v e s i n f o r m a t i o n a b o u t t r a n s i t o r y a n d s p o n t a n e o u s e l e c t r o c a r d i o g r a p h i c e v e n t s o n l y d u r i n g t h e p e r i o d o f e x a m i n a t i o n , u s u a l l y 2 4 h o u r s . O f t e n c e r t a i n t y p e s o f a r r h y t h m i a s , s o m e t i m e s s e v e r e o n e s , a r e n o t r e g i s t e r e d d u e t o t h e i r n o n - o c c u r 'r e n c e d u r i n g t h e t i m e o f r e c o r d i n g . B e c a u s e o f t h i s , d e p e n d i n g o n w h a t o n e i s t r y i n g t o d o c u m e n t , t h e t i m e o f s t u d y m a y b e e x t e n d e d , e i t h e r s e q u e n t i a l l y o r i n t e r m i t t e n t l y . I n g r o u p s o f p a t i e n t s w i t h o u t a p p a r e n t c a r d i o p a t h y , a r r h y t h m i a s a n d / o r t r a n s i t o r y d i s t u r b a n c e s o f t h e a t r i o v e n t r i c u l a r c o n d u c t i o n a r e a l s o o b s e r v e d w h i c h , i n s p i t e o f t h e l e s s e r p e r - h o u r f r e q u e n c y , c o u l d s h o w u p i n a r e p e t i t i v e m a n n e r ( p a i r s a n d n o n -s u -s t a i n e d v e n t r i c u l a r t a c h y c a r d i a ) ( 6 , 4 0 ) , w i t h a s i m i l a r p r o g n o s i s t o t h o s e w i t h o u t a r r h y t h m i a ( 2 1 ) . T h e s e f i n d i n g s d e m o n s t r a t e t h a t t h e p r o g n o s i s o f i s o l a t e d f i n d i n g s o f a r r h y t h m i a i n p r o l o n g e d E C G o b s e r v a t i o n s i s a l s o d e p e n d e n t u p o n o t h e r f a c t o r s , s u c h a s : d e g r e e o f v e n t r i c u l a r d y s f u n c t i o n ( 4 ) , a n e u r y s m a t i c a l t e r a t i o n s o f t h e l e f t v e n t r i c l e ( 9 ) , a n d a u t o m a t i c i m b a l a n c e ( 8 ) . A s h a s a l r e a d y b e e n c o m m e n t e d i n o t h e r a r t i c l e s i n t h i s e d i t i o n , f r o m t h e c l i n i c a l p o i n t o f v i e w , C h a g a s ' d i s e a s e d e m o n s t r a t e s t w o f o r m s :
a ) A c u t e f o r m b ) C h r o n i c f o r m
1 ) i n d e t e r m i n a t e 2 ) d i g e s t i v e 3 ) c a r d i a c
I n t h i s r e v i s i o n w e w i l l o n l y d e a l w i t h t h e c h r o n i c a n d i n d e t e r m i n a t e f o r m s .
INDETERMINATE
FORM
T h e s i l e n t s p e c i f i c i n f e c t i o n , s h o w i n g a n o r m a l c o n v e n t i o n a l E C G r e a d i n g , a n d n o r m a l r a d i o g r a p h s o f t h e t h o r a x , s t o m a c h a n d c o l o n , i s c o n s i d e r e d t h e i n d e t e r m i n a t e f o r m . H o w e v e r , w h e n s t u d y i n g s u c h c a s e s w i t h m o r e r e f i n e d m e t h o d s , i n v a s i v e o r n o n - i n v a s i v e , m a n y p a t i e n t s a l r e a d y e x h i b i t c a r d i a c a l t e r a t i o n s ( 2 5 , 2 9 , 3 3 ) .
I n t h e p u b l i c a t i o n s c o n s u l t e d ( 1 0 , 1 8 , 2 7 , 2 9 , 3 3 ) , a s i m i l a r i t y c a n b e o b s e r v e d w i t h r e g a r d t o i n d i v i d u a l s w i t h o u t c a r d i o p a t h y , w i t h r e g a r d t o t h e i n c i d e n c e o f v e n t r i c u l a r e x t r a s y s t o l e s , t h e n u m b e r o f v e n t r i c u l a r e x t r a s y s t o l e s / h o u r a n d c o m p l e x i t y , e x c e p t i n t h e r a r e c a s e s w h e r e f r e q u e n t ( > 3 0 / h ) ( 2 9 ) v e n t r i c u l a r e x t r a s y s t o l e s w e r e o b s e r v e d . H o w e v e r , i t i s n o t k n o w n i f t h i s l a s t f i n d i n g r e l a t e s t o a g r e a t e r d e g r e e o f c a r d i a c c o m p r o m i s e o r u n f a v o r a b l e e v o l u t i o n , i n r e l a t i o n t o t h o s e w h e r e a r r h y t h m i a w a s n o t o b s e r v e d o r w a s r a r e .
T h e s a m e h a p p e n e d f o r a t r i a l e x t r a s y s t o l e s , s i n u s p a u s e s , a n d s e c o n d d e g r e e t y p e I a t r i o v e n t r i c u l a r b l o c k a g e s , t h e s e l a s t t w o a l t e r a t i o n s o c c u r r i n g r a r e l y .
A s a l r e a d y n o t e d , o n e o f t h e c l i n i c a l c h a r a c t e r i s t i c s o f t h i s g r o u p i s s i l e n t a n d p r o l o n g e d e v o l u t i o n . N e v e r t h e l e s s , s o m e o f t h e c a r d i a c a l t e r a t i o n s i d e n t i f i e d w i t h i n v a s i v e m e t h o d s s h o w a h i g h r i s k p o t e n t i a l ( 2 ) . T h u s , e v e n w i t h o u t h a v i n g c o n c l u s i v e i n f o r m a t i o n , t h e f i n d i n g o f p o t e n t i a l l y m a l i g n a n t a r r h y t h m i a s p o i n t s t o a n a m p l i f i c a t i o n o f t h e i n v e s t i g a t i o n o f p o s s i b l e c a r d i a c c o m p r o m i s e , b e s i d e s t h e i n t r o d u c t i o n o f t h e r a p e u t i c p r o c e d u r e s , i f n e c e s s a r y . O n t h e o t h e r h a n d , t h e a b s e n c e o f a r r h y t h m i a s o f r i s k c o u l d s e r v e a s a f a v o r a b l e m e d i c a l a r g u m e n t i n c a s e s w h e r e a n e m p l o y e r i s r e f u s i n g t o a d m i t i n d i v i d u a l s w i t h p o s i t i v e s e r o l o g i c t e s t s , i n t h i s w a y a v o i d i n g t h e u n d e r e m p l o y m e n t o f l a r g e n u m b e r s o f p r o d u c t i v e i n d i v i d u a l s ( 1 0 ) .
CHRONIC
FORM
T h e a n a t o m i c a l s u b s t r a t e o f c h r o n i c c h a g a s i c c a r d i o p a t h y i s c h r o n i c f i b r o u s m y o c a r d i t i s , p r o g r e s s i v e a n d d i f f u s e , t h a t g r a d u a l l y d e s t r o y s t h e m y o c a r d i a l f i b e r s , n o t j u s t t h e m u s c u l a r f i b e r s b u t a l s o t h o s e o f t h e s i n u s a l n o d e a n d c o n d u c t i o n t i s s u e . B e s i d e s t h i s , t h e a g g r e s s i o n a g a i n s t t h e g a n g l i o n a n d t h e n e r v e e n d i n g s ( 2 3 ) p r o d u c e s m o d i f i c a t i o n s i n t h e a u t o m a t i c r e s p o n s e ( 2 8 ) . T h u s , c h r o n i c c h a g a s i c c a r d i o p a t h y p r o d u c e s t h e l e s i o n s n e c e s s a r y f o r t h e d e v e l o p m e n t o f v a r i o u s e l e c t r o c a r d i o g r a p h i c d i s t u r b a n c e s , p r i n c i p a l l y c a r d i a c a r r h y t h m i a s , e i t h e r p e r s i s t e n t o r t r a n s i t o r y ( 9 ) .
T h e e l e c t r o c a r d i o g r a p h i c a l t e r a t i o n s m o s t f r e q u e n t l y f o u n d i n c h r o n i c C h a g a s i c c a r d i o p a t h y a r e r i g h t b u n d l e -b r a n c h b l o c k , a n t e r o s u p e r i o r d i v i s i o n b l o c k , n e g a t i v e T w a v e , a n d v e n t r i c u l a r s y s t o l e s ( 3 5 , 3 9 ) . T h e b a t h m o d r o m o t r o p i c a l t e r a t i o n s o f g r e a t e s t p r o g n o s t i c i m p o r t a n c e a r e f i b r i l l a t i o n a n d a t r i a l f l u t t e r , t o t a l a t r i o v e n t r i c u l a r b l o c k , c o m p l e t e l e f t b u n d l e - b r a n c h b l o c k ,
fre q u e n t
a n d
p o ly m o rp h ic
v e n tric u la r
e x tra sy sto le s,
v e n tric u la r
ta c h y c a rd ia s
a n d
a lte ra tio n s
su g g e stiv e
o f
fib ro u s
n e c ro sis,
b e sid e s
a n o m a lie s
o f th e S - T se g m e n t
a n d th e T w a v e . T h e a sso c ia tio n
o f tw o o r m o re a lte ra tio n s
w o rse n s
th e p ro g n o sis
(3 7 ). B e sid e s
th is, a c c o rd in g
to th e
o b se rv a tio n s
o f v a rio u s
a u th o rs,
c a rd io m e g a ly
a sso c ia te d
w ith
th e
sy m p to m s
o f c o n g e stiv e
c a rd ia c
in su ffic ie n c y
w o u ld
h a v e
a
w o rse
p ro g n o sis
th a n
th o se
w ith
e le c tro c a rd io g ra p h ic
a lte ra tio n s
o n ly (5 ,7 ,1 2 ,3 7 ).
G u e rre ro
(1 7 ) e t a I., c o m p a rin g
p a tie n ts w ith c h a g a sic
c a rd io p a th y
a n d o th e r m y o c a rd io p a th ie s,
d e m o n stra te d
th a t
th e
d e g re e
o f
v e n tric u la r
d y sfu n c tio n
w a s
th e
m o st
im p o rta n t
in d e p e n d e n t
p ro g n o stic
fa c to r.
C o m p le x
v e n tric u la r
a rrh y th m ia
h a s a d d itio n a l
lim ite d
im p o rta n c e
in p a tie n ts
w ith
d e p re sse d
d ia sto lic
fu n c tio n
o f th e
le ft
v e n tric le ..
T h e o c c u rre n c e
o f a rrh y th m ia s,
in te rm s o f fre q u e n c y /
h o u r a n d re p e titiv e n e ss,
in c re a se s
p ro p o rtio n a lly
w ith th e
d e g re e
o f c a rd ia c
c o m p ro m ise
v e rifie d
b y c o n v e n tio n a l
e le c tro c a rd io g ra m .
T h e y
a re le ss fre q u e n t
in p a tie n ts
w ith th e c h ro n ic
fo rm
w ith
m in im u m
E C G
a lte ra tio n s
a n d m o re fre q u e n t
a n d
re p e titi v e w h e n
th e
p a tie n t
d e m o n stra te s
b u n d le
-b ra n c h -b lo c k a n d v e n tric u la r
e x tra sy sto le s
(7 ,1 0 ,1 7 ,2 7 ,3 7 ).
A re la tio n sh ip
b e tw e e n
fre q u e n c y
a n d c o m p le x ity
o f v e n tric u la r
a rrh y th m ia
a n d th e d e g re e
o f d y sfu n c tio n
o f th e
le ft v e n tric le
w a s
o b se rv e d
b y S a n ta n a
(3 7 )
a n d
C a rra sc o
(7 ). T h e
fo rm e r
c a lls
a tte n tio n
b e c a u se
o f its
g re a te r
in c id e n c e
in a g e g ro u p s
u n d e r
(2 0 ), w h ic h
d iffe rs
sig n ific a n tly
fro m
th o se
in d iv id u a ls
w ith o u t
c a rd io p a th y
(4 0 ).
In
C h a g a s'
d ise a se ,
a s
in
o th e r
c a rd io p a th ie s,
v e n tric u la r
a rrh y th m ia
p re se n ts
g re a t
v a ria b ility ,
w h ic h
sh o u ld
b e ta k e n
in to a c c o u n t
in p o p u la tio n
e v a lu a tio n s
a s
w e ll
a s
in
th e ra p e u tic
c o n tro l.
A c c o rd in g
to
o u r
o b se rv a tio n s,
th e n u m b e r o f v e n tric u la r
e x tra sy sto le s/h o u r
h a s
a c irc a d ia n
c h a ra c te r
a n d
te n d s
to
b e
re la te d
to
v a ria tio n s
o f c a rd ia c
fre q u e n c y
p e r h o u r. T h e sa m e p a tie n t
sh o w s
a v a ria tio n
o f 5 8 .4 %
in th e n u m b e r
o f v e n tric u la r
e x tra sy sto le s/h o u r
w h e n
w e c o m p a re
2 c o n se c u tiv e
2 1
h o u r
d u ra tio n
re c o rd in g s.
In
sh o rte r
re c o rd in g s,
th e
v a ria tio n
is so g re a t th a t it d o e sn 't
e v e n a llo w
c o m p a riso n
(7 ).
W ith
re g a rd
to th e o th e r
a rrh y th m ia s,
sin u s
p a u se s,
a tria l
e x tra sy sto le s
a n d
a trio v e n tric u la r
b lo c k s
a re
le ss
c o m m o n ly
c ite d in th e lite ra tu re ,
p ro b a b ly
b e c a u se
o f th e ir
le sse r
c lin ic a l
im p o rta n c e ,
e v e n
th o u g h
th e ir
p a tte rn
o f
d istrib u tio n
is sim ila r
to th a t o f v e n tric u la r
e x tra sy sto le s
(1 0 ,2 4 ).
T h e re la tio n sh ip
b e tw e e n
sy m p to m s
a n d v e n tric u la r
a rrh y th m ia
o b se rv e d
th ro u g h
H o lte r's
m e th o d
w a s stu d ie d
b y
M e n d o n ~ a
(3 1 )
a n d
R a ssi
Jr.
(3 4 ),
w h o
n o te d
a
sig n ific a n tly
g re a te r
n u m b e r
o f v e n tric u la r
e x tra sy sto le s
in p a tie n ts
w ith sy m p to m s
o f sy n c o p e
a n d n e a r-sy n c o p e .
In B ra z il, c h a g a sic
c a rd io p a th y
c o n stitu te s
o n e o f th e
m o st
fre q u e n t
c a u se
fo r
th e
in d ic a tio n
o f
a rtific ia l
p a c e m a k e r
im p la n ts.
H o lte r's
m e th o d
is
o n e
o f
th e
p rin c ip a l
to o ls u se d , b o th to c o n firm
th e n e c e ssity
o f th e
p ro c e d u re
a n d to d e te rm in e
th e ty p e o f stim u la tio n
n e e d e d ,
a s w e ll a s to fo llo w -u p
th e p a tie n t
a fte r th e im p la n t.
In th e
fo llo w -u p
a fte r
th e
im p la n t
its
u tility
ra n g e s
fro m
c la rific a tio n
o f sy m p to m s,
w h ic h
c o u ld
b e d u e to fa u lty
..
.,
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F igure 1 - T racing of a subject w ith an artificial ventricular pacem aker. T he pacem aker w as placed in the subject w ho had syncope attacks because of episodes of com plete atria-ventricular block of C hagasic nature. T he subject presented a non-sustained ventricular tachycardia w ith 13 beats during H olter testing (C M S lead).
functioning
of the stim ulation
system as w ell as to periods
of ventricular
tachycardia
(14) to orientation
for better
program m ing.
It is also very effective
for identification
of
interm ittent
defects. N orm ally
the latter are not diagnosed
during a conventional
electronic
evaluation
(for exam ple,
interm ittent
loss
of com m and,
m icrofractures
in the
electrodes,
increases
in the stim ulation
threshold,
external
interference
etc.) (Fig. 1).
V arious tests of autom atic
function have already been
applied on patients w ith chronic chagasic cardiopathy
(28).
Currently
it is possible
to study the variability
of cardiac
frequency
w ith H olter
recordings.
This technique
allow s
evaluation
of the autom atic
activity
of the sinus node and
has been
used
as an indicator
of risk
in patients
w ith
coronary
disease (22), and as an early w arning
of visceral
neuropathy
in diabetics
(11). A s of yet, w e don't have data
about its prognostic
im portance
for patients
w ith Chagas'
disease.
Technological
advances
have
perm itted
the
incorporation
of new techniques
into the H olter
m ethod.
O ne of them is its utilization
for obtaining
high resolution
electrocardiogram s.
A lready
w ell established
as a m ethod
for evaluation
of risk in patients
w ith coronary
disease,
being capable
of identifying
those w ith the possibility
of
developing
ventricular
tachycardial
crisis and sudden death
(13), it has also been
useful
w ith Chagas'
disease
(32).
N evertheless,
the evaluation
of Chagas'
disease
using
H olter's
m ethod
is still in the developm ent
phase (20).
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