IJC Hea & Vascula u e 43 (2022) 101138
A ailable online 14 Oc obe 2022
2352-9067/© 2022 The Au ho s. Published by Else ie B.V. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-
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The a ial ib illa ion bu den du ing he blanking pe iod is p edic i e o
ime o ecu ence a e ca he e abla ion
Ped o Sil a Cunha
a
,
b
,
*
,
1
, Guilhe me Po ugal
a
,
b
,
1
, S´
e gio La anjo
a
,
c
,
d
,
1
, Ma a Al es
c
,
e
,
1
,
Ana Luísa Papoila
c
,
e
,
1
, B uno Valen e
a
,
1
, Ana So ia Delgado
a
,
1
, Ana Lousinha
a
,
1
,
Ma ga ida Paulo
a
,
1
, Manuel B ´
as
a
,
1
, C´
a ia Gue a
a
,
1
, Rui C uz Fe ei a
a
,
1
,
M´
a io Ma ins Oli ei a
a
,
b
,
1
a
A hy hmology, Pacing and Elec ophysiology Uni , Ca diology Se ice, San a Ma a Hospi al, Cen o Hospi ala Uni e si ´
a io de Lisboa Cen al, Lisbon, Po ugal
b
LisbonSchool o Medicine, Uni e sidade de Lisboa, Lisbon, Po ugal
c
NOVAMedical School/Faculdade de Ciˆ
encias M´
edicas, Uni e sidade No a de Lisboa and CEAUL (Cen e o S a is ics and I s Applica ions), Lisbon, Po ugal
d
Comp ehensi eHeal h Resea ch Cen e , Uni e sidade NOVA de Lisboa, Lisbon, Po ugal
e
Epidemiology and S a is ics Uni , Resea ch Cen e, Cen o Hospi ala de Lisboa Cen al, Lisbon, Po ugal
ARTICLE INFO
Keywo ds:
A ial ib illa ion
Pulmona y ein isola ion
A hy hmia ecu ence
A hy hmia bu den
Blanking pe iod
Ca he e abla ion
ABSTRACT
Objec i e: This s udy aimed o assess whe he a ial ib illa ion (AF) occu ence o i s co esponding daily mean
bu den (in minu es/day) du ing he mid o la e blanking pe iod a e pulmona y ein isola ion (PVI), p edic s AF
ecu ence.
Me hods: Analysis o consecu i e i s PVI abla ion pa ien s unde going p olonged elec oca diog am (ECG)
moni o ing du ing he second and hi d mon hs a e PVI. The clinical a iables, o al AF bu den, and hei
ela ionship wi h ime o ecu ence we e s udied.
Resul s: 477 pa ien s wi h a mean age o 56.9 (SD =12.3) yea s (63.7 % male; 71.7 % pa oxysmal AF), om
which 317 (66.5 %) had an ex e nal e en eco de be ween 30 and 90 days a e abla ion. Median ollow-up o
16.0 (P 25:12.0: P 75:33.0) mon hs, 177 (37 %) pa ien s had an AF ecu ence, wi h 106 (22.2 %) ha ing he i s
episode a e 12 mon hs o ollow-up. In he g oup o pa ien s wi h an e en eco de , 80 (25.2 %) had AF
documen ed du ing he blanking pe iod. Mul i a iable analysis showed ha AF du ing he blanking pe iod was
associa ed wi h a 4- old highe isk o ecu ence (HR: 3.98; 95 %CI: 2.95–5.37), and, compa ed o pa ien s in
sinus hy hm, hose wi h an AF bu den ≥23 min/day had an app oxima ely 7- old highe isk o ecu ence (HR
es ima e: 6.79; 95 %CI: 4.56–10.10).
Conclusions: The p obabili y o expe iencing AF ecu ence can be p edic ed by a ial achya hy hmia episodes
du ing he second and hi d mon hs a e PVI. A ial a hy hmias bu den >23 min/day has a high p edic i e
abili y o ecu ence.
1. Backg ound
A ial ib illa ion (AF) is he mos common sus ained a hy hmia and
is associa ed wi h a subs an ial economic bu den and signi ican
mo bidi y and mo ali y [1,2]. In he pas wo decades, he knowledge o
AF pa hophysiology has led o signi ican de elopmen s in he ea men
op ions, pa icula ly ega ding ca he e abla ion [3,4,5]. Abla ion,
based on pulmona y ein isola ion (PVI), ep esen s an essen ial
hy hm-con ol s a egy o he managemen o pa oxysmal, d ug-
e ac o y AF, being one o he mos common ca diac abla ion p oced-
u es pe o med wo ldwide.
A undamen al aspec a e PVI is he assessmen o a hy hmic
ecu ence. AF can occu in he i s weeks o mon hs a e PVI o e en
a e a long- e m pe iod ee o AF [6]. The i s h ee mon hs a e PVI is
known as he blanking pe iod, and a ial achya hy hmias (AT/AF)
du ing i is conside ed a ansi o y phenomenon wi hou clinical
* Co esponding au ho a : San a Ma a Hospi al, Ca diology Se ice, A hy hmology, Pacing, and Elec ophysiology Uni , R. de San a Ma a 50, 1169-024 Lisboa,
Po ugal.
E-mail add ess: [email p o ec ed] (P. Sil a Cunha).
1
This au ho akes esponsibili y o all aspec s o he eliabili y and eedom om bias o he da a p esen ed and hei discussed in e p e a ion.
Con en s lis s a ailable a ScienceDi ec
IJC Hea & Vascula u e
jou nal homepage: www.sciencedi ec .com/jou nal/ijc-hea -and- ascula u e
h ps://doi.o g/10.1016/j.ijcha.2022.101138
Recei ed 31 July 2022; Recei ed in e ised o m 22 Sep embe 2022; Accep ed 11 Oc obe 2022
IJC Hea & Vascula u e 43 (2022) 101138
2
signi icance in p edic ing la e AF ecu ence. Howe e , in ecen yea s,
he clinical implica ion o he occu ence o AT/AF in his pe iod has
come o be alued.
The incidence o AT/AF is highes in he immedia e pos -abla ion
pe iod and p og essi ely dec eases a e ha [7,8]. Since he obse a-
ion by O al e al. in 2002 [9], di e en s udies ha e consis en ly ound
ha ea ly ecu ence o AT/AF occu s mainly du ing he i s wo weeks
a e PVI [10,11]. This means ha AT/AF as a p edic o o la e e-
cu ences p obably became mo e signi ican a e he i s mon h [12].
The e o e, we conduc ed his s udy o in es iga e he incidence o AT/
AF du ing he ea ly pe iod a e PVI by using an ex e nal e en loop
eco de and i s ela ionship wi h ecu ence a e and ime o AF
occu ence du ing ollow-up.
2. Me hods
2.1. S udy popula ion
We s udied 477 consecu i e pa ien s wi h symp oma ic d ug-
e ac o y pa oxysmal (PAF) o pe sis en (PsAF) AF who ecei ed an
index AF ca he e abla ion be ween 05/2005 and 02/2020 in he Cen o
Hospi ala de Lisboa Cen al. Subjec da a we e excluded om he
cu en analysis i pa ien s we e diagnosed wi h long-s anding pe sis en
AF (con inuous AF >12 mon hs), had incomple e baseline da a e-
po ed, o we e edo p ocedu es. AF was classi ied as PAF i a hy hmia
episodes e mina ed spon aneously, o wi h in e en ion wi hin se en
days o onse , o as PsAF i he episodes we e sus ained, las ed longe
han se en days, bu <12 mon hs [1].
The hospi al e hics commi ee app o ed he s udy p o ocol (E hics
Commi ee app o al numbe 974/2020). All pa icipan s p o ided
w i en in o med consen o da a collec ion, and he s udy was con-
duc ed acco ding o he Decla a ion o Helsinki guidelines.
2.2. Abla ion p ocedu e
E e y pa ien unde wen a ou ine p ep ocedu al ans ho acic
echoca diog am o e alua e le en icula ejec ion ac ion le a ial
dimensions, sc een o s uc u al hea disease, and compu ed omog-
aphy o magne ic esonance imaging (wi h he segmen a ion o he le
a ium) o assess le a ial ana omy and o exclude he p esence o
in aca diac h ombi. Addi ionally, i he men ioned imaging s udy was
pe o med >48 h be o e abla ion, ansesophageal echoca diog aphy
was done on he day o he p ocedu e ( o exclusion o h ombi). Pa-
ien s unde wen abla ion a e con inued o al an icoagula ion ( o a
leas ou weeks be o e abla ion) using wa a in wi h a he apeu ic INR
(2.0–3.0) o di ec o al an icoagulan s (DOAC), wi h one dosage omi ed
in he e ening be o e he abla ion. Con inuous moni o ing o oxygen
sa u a ion and ECG we e main ained h oughou he abla ion. All p o-
cedu es we e ca ied ou unde conscious seda ion o gene al
anes hesia.
In b ie , he p o ocol s eps o adio equency ca he e abla ion
(RFCA) in he esea che s’ ins i u ion consis ed in: 1. posi ioning a
decapola ca he e h ough he igh emo al ein o guide he ans-
sep al punc u e and o pace he le a ium, 2. A anssep al punc u e by
luo oscopic guidance 3. h ee-dimensional mapping o he le a ium
pe o med wi h ei he he EnSi e Na X/Veloci y (Abbo Labo a o ies,
Abbo Pa k, IL) o CARTO (Biosense Webs e , I ine, Cali o nia) sys-
em. Radio equency applica ions we e pe o med using an open-
i iga ed- ip ca he e (FlexAbili y™, Abbo o The moCool Sma -
Touch® Su oundFlow, Biosense Webs e ) wi h poin -by-poin -lesions.
When using he c yoene gy, he abla ion balloon sys em used was he
A c ic F on ™ (Med onic, Inc., Minneapolis, MN, USA) wi h he 28-mm
balloon. Di e en c yoballoon posi ions we e assessed (by injec ing
con as in o he ein dis al o he balloon) o ensu e op imal occlusion.
Rega ding ene gy applica ions, a e success ul PVI (240 s, aiming o a
minimum empe a u e o less han −40 ◦C), an addi ional eeze-cycle
o he same du a ion was applied a he ope a o ’s disc e ion. The
ph enic ne e unc ion was checked du ing ene gy applica ion in he
igh pulmona y eins [13].
2.3. Pos abla ion e alua ion
AF ecu ence- ee su i al was he p ima y endpoin , conside ing
an AF ecu ence as any pos –90-day blanking a ial achya hy hmias
las ing 30 s o longe , sus ained symp oma ic episodes o apid palpi-
a ions, p esc ip ion o an ia hy hmic d ugs (class I o III), o epea
abla ion.
A e he abla ion p ocedu e, pa ien s we e discha ged on an ia -
hy hmic d ugs (AAD) a he ope a o ’s disc e ion, oge he wi h o al
an icoagula ion. Pa ien s we e obse ed o ou ine ollow-up in he
ou pa ien clinic 1–3 mon hs a e he p ocedu e and e e y six mon hs
(o ea lie , i symp oms) du ing he i s wo yea s pos -abla ion. A each
isi , a s anda d 12-lead ECG was ob ained. Pa ien s we e moni o ed
wi h an ex e nal loop eco de (Spide lash™ and E en scope™ 3
analysis so wa e, Mic oPo CRM, Clama , F ance) be ween 30 and 90
days a e AF abla ion. A e he blanking pe iod, pa ien s we e
ollowed-up wi h a 24-hou -Hol e a each ou pa ien isi .
AAD was con inued o six mon hs a e he abla ion p ocedu e and
was wi hd awn - excep o be a-blocke s - i he pa ien s we e ee om
a hy hmia- ela ed symp oms. O al an icoagula ion was e-e alua ed in
he hi d mon h, and he decision o con inue was based on he
CHA2DS2-VASc sco e. Clinical e en s occu ing du ing he ollow-up
we e e alua ed.
2.4. S a is ical analysis
Resul s a e exp essed as mean (±s anda d de ia ion, SD), median
(P25; P75), o as equencies and pe cen ages, as app op ia e. AT/AF
bu den du ing he blanking pe iod, co esponding o he mean du a ion
ime o AT/AF pe day ( e e ed o as AF bu den), was ob ained by
di iding he numbe o minu es wi h a hy hmia by he numbe o days
o de ice use. A ime-dependen a ea unde he ROC (Recei e Ope -
a ing Cha ac e is ic) cu e was used o s udy i s disc imina i e abili y
ega ding u u e ecu ence along he ollow-up ime. The in e se
p obabili y o censo ing weigh ing (IPCW) me hod was applied o es i-
ma e hese ime-dependen a eas unde he ROC cu e. A cu -o poin
o his AF bu den ha bes p edic ed AF ecu ence was ob ained wi h
only hose pa ien s wi h an AF bu den di e en om ze o, and a new
bina y a iable was cons uc ed. Ma ingale esiduals, p ope o assess
he unc ional o m o co a ia es in he Cox p opo ional haza ds model,
we e used o iden i y his poin [14]. Time-dependen sensi i i y,
speci ici y, and posi i e and nega i e p edic i e alues we e es ima ed
o his bina y AF bu den a iable.
Two su i al analyses o s udy ime un il ecu ence we e pe o med
conside ing he p ima y exposu es: ha ing had (o no ) AF episodes
du ing he blanking pe iod, and co esponding AF bu den. Fi s ly,
Kaplan-Meie es ima o was used o ob ain ecu ence- ee su i al es-
ima es. Log- ank es was u he applied o compa e AF su i al
unc ions be ween g oups. Secondly, uni a iable and mul i a iable Cox
eg ession models we e i ed o he da a, conside ing he occu ence o
AF episodes o AF bu den, du ing he blanking pe iod, as independen
a iables in wo sepa a e mul i a iable analyses. The associa ion o
hese wo isk ac o s wi h ecu ence- ee su i al was adjus ed by
se e al co a ia es, such as age, sex, como bidi ies, episodes o
a hy hmia pa e n, and body mass index, among o he s. The p opo -
ional haza ds assump ion was checked using o mal s a is ical es s and
g aphical diagnos ics based on he scaled Schoen eld esiduals. Because
his assump ion was iola ed o he bina y a iable co esponding o
he numbe o como bidi ies (ze o o one s. ≥2), a model wi h ime-
a ying coe icien s was i ed o he da a [15].
A le el o signi icance
α
=0.05 was conside ed. All da a we e
analyzed using STATA (S a aCo p. 2017. S a a S a is ical So wa e:
P. Sil a Cunha e al.
IJC Hea & Vascula u e 43 (2022) 101138
3
Release 15. College S a ion, TX: S a aCo p LLC.) and R so wa e (R Co e
Team (2021). R: A language and en i onmen o s a is ical compu ing.
R Founda ion o S a is ical Compu ing, Vienna, Aus ia. URL h ps://
www.R-p ojec .o g/.).
3. Resul s
3.1. Baseline clinical cha ac e is ics
This e ospec i e coho s udy conside ed ou hund ed and
se en y-se en consecu i e pa ien s wi h a median ollow-up ime o 16.0
(P
25
:12.0; P
75
:33.0) mon hs. Coho ’s mean age was 56.9 (SD =12.3),
and 36.3 % we e women (Table 1). The baseline pa e n o AF was
pa oxysmal in 71.7 % and pe sis en in 28.3 %. All pa ien s unde wen
ci cum e en ial PVI. RFCA using con ac - o ce echnology was used in
295 pa ien s, and abla ion using he second-gene a ion c yoballoon in
182 pa ien s. Ca o- icuspid is hmus abla ion was pe o med in 29 pa-
ien s wi h p e ious documen a ion o ypical a ial lu e .
De ailed baseline clinical and demog aphic cha ac e is ics o he
s udy popula ion a e epo ed in Table 1.
3.2. A ial ib illa ion ecu ence
One hund ed and se en y-se en (37.1 %) pa ien s had an AF ecu -
ence, om which 106 (59.9 %) occu ed a e 12 mon hs o ollow-up.
Recu ence- ee su i al es ima e is depic ed in Fig. 1.
Conside ing he ca diac hy hm eco ded du ing he blanking pe iod
(sinus hy hm s. AF): om pa ien s wi h sinus hy hm (n =370), 99
(26.8 %) had an AF ecu ence, whe eas, in pa ien s wi h documen ed
AF (n =107, 22,4 %), 78 (72.9 %) had an AF ecu ence. Fig. 2 shows a
signi ican di e ence in ecu ence- ee su i al be ween hese wo
g oups o pa ien s (p <0.001).
3.3. E en eco de da a analysis
The ex e nal e en eco de was used by 317 pa ien s du ing he
“la e” blanking pe iod a e he abla ion p ocedu e o a median ime o
21 (min =5, max =34) days. Rega ding AT/AF bu den, 237 pa ien s
had no AT/AF (ze o minu es), and 80 (25.2 %) wi h AT/AF episode(s)
had a median o 29.5 (P
25
=6.9, P
75
=96.2) minu es o a hy hmia
bu den. The ime-dependen disc imina i e abili y o AF bu den du ing
he blanking pe iod o dis inguish be ween pa ien s who elapsed om
hose who did no was cha ac e ized by he ollowing ime-dependen
a ea unde he cu e o he ecei e -ope a o cha ac e is ic o ( ime
in mon hs) 6 =85.4 %, =9, 78.3 %, =12, 71.2 %, =24, 68.9 % (see
Table 2). A dec easing end in he a ea unde he ROC cu e may be
obse ed.
Using he da a co esponding o he 80 pa ien s wi h an AT/AF
bu den di e en om ze o, in whom 67.5 % (n =54) had a ecu ence, a
cu -o poin o his bu den (AF mean du a ion ime pe day) was
de e mined (Fig. 3).
In his igu e, he smoo h unc ion should be linea o sa is y he
s anda d Cox p opo ional haza ds model linea i y assump ion [14].
Howe e , his g aphical check shows a nonlinea i y and, acco dingly,
al hough his co a ia e could be modeled wi h a nonlinea unc ion, we
p oceeded o i s disc e iza ion o clinical p ac ice use. We conside ed
he cu -o poin whe e he smoo h unc ion c osses he e e ence line
(23 min o AF pe day), below which he isk o ecu ence is lowe . A
24 mon hs o ollow-up, his a iable (AF bu den <23 min s. AF
bu den ≥23 min) showed a sensi i i y o 33.4 %, a speci ici y o 91.1 %,
and posi i e and nega i e p edic i e alues o 60.0 % and 77.5 %,
espec i ely (Table 3).
A ca ego ical a iable wi h h ee ca ego ies (no AF bu den, wi h
bu den <23 min pe day, ≥23 min pe day) eme ged om he o me
analysis. No AF bu den ca ego y includes pa ien s wi h ze o minu es o
a hy hmia (n =237) and hose ha did no use he ex e nal e en
eco de bu had no clinical AF episodes (n =133). The compa ison o
ecu ence- ee su i al o hese h ee g oups o pa ien s is shown in
Fig. 4.
3.3.1. Uni a iable analysis
Resul s o he uni a iable analysis o AF ecu ence a e shown in
Table 4. Va iables ha a ained a p- alue <0.25 we e selec ed o he
mul i a iable s udy.
3.3.2. Mul i a iable analysis
Rega ding he occu ence o AF episode(s) du ing he blanking
pe iod, no mul i a iable model was achie ed, and only his a iable
emained in he inal model. Acco dingly, he esul s a e he same as
hose o he uni a iable analysis (Table 3) and pa ien s ha had AF
episodes du ing he blanking pe iod had app oxima ely a 4- old highe
isk o ecu ence (HR: 3.98; 95 %CI: 2.95–5.37); p <0.001).
Rega ding AF bu den du ing he blanking pe iod, esul s o he
mul i a iable analysis a e p esen ed in Table 4. A iola ion o he p o-
po ional haza ds assump ion was obse ed o he numbe o como -
bidi ies du ing he mul i a iable modeling p ocess o he da a using he
Cox eg ession model (supplemen a y ma e ial Fig. 1).
Mul i a iable analysis esul s showed ha , compa ed o pa ien s
wi h sinus hy hm, hose wi h an AF bu den ≥23 min/day had an
app oxima ely 7- old highe isk o ecu ence (HR es ima e: 6.79; 95 %
CI: 4.56–10.10), while o pa ien s wi h an AF bu den <23 min/day his
isk inc ease was lowe (HR es ima e: 2.60; 95 %CI: 1.54–4.47).
Changing he e e ence ca ego y o an AF bu den ≥23 min/day
enabled he compa ison o he isk ecu ence o pa ien s wi h an AF
bu den <23 min/day wi h hose wi h a highe bu den. Acco dingly,
pa ien s wi h a lowe AF bu den had a 61 % dec ease in he isk o
ecu ence when compa ed wi h hose wi h an AF bu den ≥23 min/day
(HR es ima e: 0.39; 95 %CI: 0.21–0.70). Rega ding he numbe o
como bidi ies, ha ing mo e han one como bidi y inc eases he isk o
ecu ence, al hough his inc ease was only s a is ically signi ican
beyond ≈30 mon hs o ollow-up a e ca he e abla ion (HR es ima e:
3.25; 95 %CI: 1.70–6.23).
4. Discussion
4.1. Main indings
The main indings o he p esen s udy a e 1) pa ien s wi h AT/AF
episodes las ing >30 s du ing he “la e” blanking pe iod (be ween 31
Table 1
Popula ion cha ac e is ics.
Va iables Numbe o pa ien s
(n ¼477)
Pa oxysmal AF, n (%) 342 (71.7)
Male sex, n (%) 304 (63.7)
Mean age (SD), yea s 56.9 (12.3)
Mean LA diame e (SD), mm 43.9 (6.9)
Mean le a ial indexed olume (SD), ml/m
2
38.3 (12.1)
Median CHA
2
DS
2
-VASc (P
25
; P
75
) 1.0 (1.0; 2.0)
Mean Body Mass Index (SD), Kg/m
2
28.15 (4.88)
Hype ension, n (%) 281 (58.9)
Hype choles e olemia, n (%) 135 (28.3)
Diabe es melli us, n (%) 35 (7.3)
Co ona y a e y disease, n (%) 25 (5.2)
OSAS, n (%) 52 (10.9)
Hea ailu e, n (%) 44 (9.2)
Ch onic kidney disease, n (%) 5 (1.0)
P e ious S oke/TIA, n (%) 17 (3.6)
P e ious pulmona y/pe iphe al Embolism, n (%) 7 (1.5)
Median ollow-up (P
25
; P
75
), mon hs 16.0 (12.0; 33.0)
Legend: AF =a ial ib illa ion, LA =le a ium, OSAS =obs uc i e sleep
apnea synd ome, TIA = ansien ischemic acciden , SD =s anda d de ia ion,
P
25
=25 h pe cen ile, P
75
=75 h pe cen ile.
P. Sil a Cunha e al.
IJC Hea & Vascula u e 43 (2022) 101138
4
and 90 days pos -PVI) had a signi ican ly highe isk o long- e m AF
ecu ence han hose wi h sinus hy hm du ing all blanking pe iod, 2) a
o al bu den o AT/AF abo e 23 min du ing he blanking pe iod was
co ela ed wi h an app oxima ely 7- old isk o AF ecu ence. Also,
ha ing mo e han one como bidi y signi ican ly inc eases he isk o
ecu ence beyond 30 mon hs a e ca he e abla ion.
In he ea ly pe iod a e AF abla ion, he occu ence o AT/AF is a
common inding bu may no necessa ily imply long- e m abla ion
ailu e. The i s h ee mon hs a e abla ion a e usually no conside ed
ega ding ein e en ion and p ocedu al success epo s [16,17].
Fu he mo e, i has been accep ed ha he incidence o ea ly AT/AF
episodes is equen soon a e he abla ion, dec easing in he ollowing
days [18]. Indeed, he numbe o a ial a hy hmias dec eases du ing he
3-mon h blinding pe iod [19,20].
Fig. 1. Kaplan-Meie es ima e o ecu ence- ee su i al (es ima ed median =47 mon hs; 95 % CI: 38.71–55.29).
Fig. 2. Kaplan-Meie es ima es ecu ence- ee su i al acco ding o ca diac hy hm du ing he blanking pe iod: sinus hy hm (g een line) and a ial ib illa ion ( ed
line). (Fo in e p e a ion o he e e ences o colou in his igu e legend, he eade is e e ed o he web e sion o his a icle.)
P. Sil a Cunha e al.
IJC Hea & Vascula u e 43 (2022) 101138
5
Al hough he p e alence o AT/AF is signi ican du ing he blanking
pe iod, wi h a ious s udies iden i ying>50 % o he pa ien s ha ing an
ea ly ecu ence, depending on he ype o hy hm moni o ing used,
a good p opo ion o pa ien s will s ill be ee o AF a p olonged
ollow-up [6,16,17]. Howe e , i has been shown ha la e ecu ence is
mo e equen in pa ien s who expe ience AT/AF du ing he blanking
pe iod [20]. The e o e, pa ien s wi hou a ial a hy hmias du ing he
con en ional 3-mon h blanking pe iod a e mo e likely o be AF- ee a
long- e m ollow-up.
P e ious s udies ha e u ilized a wide ange o du a ions o he
blanking pe iod pos -abla ion, making i di icul o de ine he op imal
du a ion o his pa icula e alua ion pe iod. Also, he deg ee o
a hy hmia bu den ha be e p edic s longe - e m success has no been
quan i ied.
In ou s udy, we decided o analyze he p edic i e alue o AT/AF
occu ence du ing he “la e” blanking pe iod a e he abla ion p o-
cedu e (be ween he 31s and he 90 h day) and o assess he bes cu -o
poin o he AT/AF bu den ega ding he p edic ion o la e AF ecu -
ence. The o e all p e alence o AF ecu ence was 37,1 % du ing a
long- e m ollow-up, wi h a good pe o mance o bina y AF bu den
du ing he blanking pe iod as a diagnos ic es o AF ecu ence. An
a hy hmia bu den >23 min/day had a nega i e p edic i e alue o
91,3 % and a posi i e p edic i e alue o 40,6 % in he p edic ion o la e
AF ecu ence.
I is impo an o highligh ha close moni o ing o ecu ence
du ing he blanking pe iod is uncommon [21], which may make ou
s udy pa icula ly in e es ing since we ca ied ou p ospec i ely and
sys ema ically an ex e nal loop eco ding in a signi ican pe cen age o
ou pa ien popula ion.
4.2. Mechanisms o ea ly a ial a hy hmias du ing he blanking pe iod
The unde lying pa hophysiological p ocesses esponsible o ea ly
AT/AF ecu ence a e no en i ely known. Se e al explana ions [22]
ha e been sugges ed o cause a hy hmias in he ea ly phase a e AF
abla ion. T ansien ac o s [23,24,25], like in lamma ion, au onomic
imbalance, lesions o ma ion, o mo e ex ensi e abla ions, may
con ibu e o he equen occu ence o AT/AF in he ea ly pe iod pos -
AF abla ion. A hy hmogenesis du ing he blanking pe iod seems o be a
dynamic p ocess. To a oid he acu e e ec s o ene gy deli e y o he
a ial issue, we included pa ien s s udied wi h he long-du a ion
ex e nal moni o ing a e he i s 30 days ollowing he abla ion
p ocedu e.
4.3. P edic i e alue o ea ly a ial a hy hmias ecu ence
The e en ex e nal loop eco de is an easily accessible complimen-
a y exam sui able o pe o ming du ing he blanking pe iod. Ou s udy
showed a 25,2 % incidence o AT/AF while moni o ing ca diac hy hm
du ing he la e blanking pe iod. O e all, hese pa ien s had app oxi-
ma ely a 4- old highe isk o la e ecu ence. The o iginali y o ou wo k
is ha he cu -o in e al o 23 min pe day signi ican ly inc eased he
incidence o AF ecu ence, wi h pa ien s showing almos a 7- old
chance compa ed o hose wi hou ea ly AT/AF de ec ion.
In ou analysis, no only eedom om ea ly ecu ence is a guide o
an icipa ing ou comes, bu also he o al bu den o a ial a hy hmias is
an impo an pa ame e o be acknowledged.
The e o e, he egula use o long-du a ion moni o ing wi h an
ex e nal loop eco de can be bene icial, as i allows he assessmen o a
simple pa ame e o e alua ing he isk o AF ecu ence. The ea ly
occu ence o AF abo e he e e ed cu -o bu den can be seen as a ed
lag ha can e en ually jus i y a mo e in ensi e ollow-up, main enance
o AAD, and decide ch onic an icoagula ion (combined wi h he CHADs-
VASc sco e) o ul ima ely conside unde going a e-abla ion p ocedu e.
5. Limi a ions
This s udy had se e al limi a ions. Fi s , his s udy was designed as a
single-cen e p ospec i e s udy; hus, i is necessa y o alida e he e-
sul s om a p ospec i e s udy wi h la ge sample size. Secondly, we used
s anda d nonin asi e ollow-up me hods, no in asi e me hods (e.g., an
Table 2
Pe o mance o bina y AF bu den du ing he blanking pe iod as a diagnos ic es
o AF ecu ence.
Time (mon hs) Sensi i i y (%) Speci ici y (%) PPV (%) NPV (%)
=6 68.8 88.4 24.3 98.1
=9 58.5 89.6 37.0 95.4
=12 47.1 88.9 40.6 91.3
=24 33.4 91.1 60.0 77.5
Legend: AF-a ial ib illa ion; PPV: Posi i e P edic i e alue; NPV: Nega i e
P edic i e alue.
Fig. 3. The plo o ma ingale esiduals e sus AF mean du a ion ime pe day
o assess he unc ional o m o his co a ia e in he Cox p opo ional haza ds
model. The supe imposed smoo h unc ion in his plo is ep esen ed by he
solid black line (wi h a co esponding 95 % con idence in e al – dashed lines).
Table 3
Uni a iable analysis esul s.
Va iables HR es ima e 95 % CI p- alue
Female sex 1.26 0.93–1.70 0.145
Age 1.02 1.01–1.03 0.001
Body Mass Index 1.03 1.01–1.06 0.018
Pa oxysmal AF 0.65 0.47–0.89 0.008
Como bidi ies (≥2) 1.40 1.04–1.87 0.027
Ana omical a ian (yes) 1.33 0.97–1.84 0.082
A e age Pla ele Volume 1.07 0.94–1.22 0.339
PDW 0.96 0.89–1.04 0.275
Monocy es/HDL a io* 1.03 1.00–1.06 0.025
Neu ophil/lymphocy e a io 0.93 0.83–1.05 0.233
Monocy e/lymphocy e a io
**
0.49 0.11–2.13 0.342
CT scan LA 1.04 1.00–1.09 0.047
AF du ing blanking pe iod 3.98 2.95–5.37 <0.001
AF bu den <23 min/day
AF bu den ≥23 min/day
2.37
6.54
1.39–4.03
4.40–9.71
0.001
<0.001
AF bu den min/day
***
1.07 1.05–1.09 <0.001
Legend: AF =a ial ib illa ion, PDW =Pla ele Dis ibu ion Wid h, HDL =
High-densi y lipop o ein, CT Compu ed Tomog aphy, LA =le a ium, HR –
Haza d Ra io, CI – Con idence In e al; * Fo each 0.001 uni inc ease; ** Fo
each 10 uni s inc ease; *** o each 30 min/day inc ease.
P. Sil a Cunha e al.

IJC Hea & Vascula u e 43 (2022) 101138
6
inse able ca diac moni o ). The e o e, de ec ing AF ecu ences a e
ca he e abla ion, ou side he eco ding pe iod, pa icula ly in cases
wi h asymp oma ic AF, is di icul , and he s udy migh unde es ima e
he ecu ence a e.
Thi dly, an i-a hy hmic d ugs we e con inued du ing he blanking
pe iod, which is an impo an con ounde .
A ou h limi a ion conce ns he low numbe o pa ien s used o
ob ain he cu -o poin o AF bu den du ing he blanking pe iod.
6. Conclusions
The p obabili y o expe iencing la e ecu ence a e PVI can be
p edic ed by a ial a hy hmias du ing he blanking pe iod, wi h a
highe likelihood i he bu den is >23 min. The blanking pe iod AF
bu den a e PVI should be in es iga ed in u u e s udies.
7. G an suppo
This wo k did no ecei e any g an s o unding.
8. E hical disclosu es
P o ec ion o human and animal subjec s. The au ho s decla e ha
he e we e no expe imen s pe o med on humans o animals o his
s udy.
Regis a ion numbe and Hospi al E hics Commi ee app o al:
numbe 974/2020.
9. Con iden iali y o da a
The au ho s decla e ha hey ollowed hei hospi al cen e ’s p o-
ocols on he pa ien da a publica ion.
10. Righ o p i acy and in o med consen
The au ho s decla e ha no pa ien da a appea in his a icle.
Decla a ion o Compe ing In e es
The au ho s decla e ha hey ha e no known compe ing inancial
in e es s o pe sonal ela ionships ha could ha e appea ed o in luence
he wo k epo ed in his pape .
Appendix A. Supplemen a y ma e ial
Supplemen a y da a o his a icle can be ound online a h ps://doi.
o g/10.1016/j.ijcha.2022.101138.
Fig. 4. Kaplan-Meie es ima es o ecu ence- ee su i al acco ding o AF bu den eco ded du ing he blanking pe iod: sinus hy hm (g een line), AF wi h a mean
du a ion ime <23 min pe day (blue line), and AF wi h a mean du a ion ime ≥23 min pe day ( ed line). Twen y-se en pa ien s wi h AF had missing alues in AF
bu den. (Fo in e p e a ion o he e e ences o colou in his igu e legend, he eade is e e ed o he web e sion o his a icle.)
Table 4
Mul i a iable analysis esul s.
Va iables HR es ima e 95 % CI p- alue
AF bu den*
AF bu den <23 min/day
AF bu den ≥23 min/day
AF bu den
**
No AF bu den (sinus hy hm)
AF bu den <23 min/day
2.60
6.79
0.15
0.39
1.54–4.47
4.56–10.10
0.10–0.22
0.21–0.70
<0.001
<0.001
<0.001
0.002
Como bidi ies
***
≥2 o ollow-up ime <≈30 mon hs
≥2 o ollow-up ime ≥ ≈30 mon hs 1.31
3.25
0.91–1.90
1.70–6.23
0.147
<0.001
Legend: AF- a ial ib illa ion; HR – Haza d Ra io, CI – Con idence In e al; *
Re e ence ca ego y: no AF bu den (sinus hy hm); ** Re e ence ca ego y: AF
bu den ≥23 min/day; *** Re e ence ca ego y: Ze o o one como bidi ies.
P. Sil a Cunha e al.
IJC Hea & Vascula u e 43 (2022) 101138
7
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