Download Enlargement of Catheter Ablation Lesions in Infant Hearts With

Enlargement of Catheter Ablation Lesions in Infant Hearts
With Cryothermal Versus Radiofrequency Energy
An Animal Study
Paul Khairy, MD, PhD; Peter G. Guerra, MD; Lena Rivard, MD; Jean-François Tanguay, MD;
Evelyn Landry, AHT; Marie-Claude Guertin, PhD; Laurent Macle, MD; Bernard Thibault, MD;
Jean-Claude Tardif, MD; Mario Talajic, MD; Denis Roy, MD; Marc Dubuc, MD
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Background—Radiofrequency catheter ablation in immature hearts has been associated with marked enlargement of
lesions over time, with potential for related late adverse events. It remains unknown whether cryothermal ablation
lesions display a similar pattern of growth.
Methods and Results—Ablation lesions (n⫽384) were performed in 32 infant miniature swine in right and left atria,
ventricles, and atrioventricular (AV) grooves preselected by a randomized factorial design devised to compare
radiofrequency and cryothermal lesions produced by 7F 4-mm electrode-tip catheters. Animals were euthanized acutely
or at 1, 6, or 12 months, according to the randomization scheme. The miniature swine weighed 8.8⫾1.2 kg and were
63⫾13 days of age at time of ablation. The minimum temperature during cryoablation was ⫺79.8⫾3.4°C and the
average temperature during radiofrequency ablation was 54.4⫾5.5°C. On morphometric analyses, no differences in the
rate of growth of ablation lesions were noted between the 2 energy modalities in atria (P⫽0.44), ventricles (P⫽0.57),
or AV grooves (P⫽0.69). Lesion volumes increased 3.3-fold in atria (95% confidence interval [CI], 2.3 to 4.3;
P⫽0.001) and 2.2-fold in ventricles (95% CI, 1.4 to 3.0; P⬍0.0001), with the difference between chambers being
nonsignificant (P⫽0.22). Whereas the depth of AV groove lesions increased over time (1.9-fold; 95% CI, 1.5 to 2.3;
P⬍0.0001), lesion volumes did not enlarge significantly (1.5-fold; 95% CI, 0.4 to 2.6; P⫽0.45).
Conclusions—Ablation lesions produced by cryothermal energy in immature atrial and ventricular myocardium enlarge to
a similar extent to radiofrequency ablation. In contrast, AV groove lesion volumes do not increase significantly with
either energy modality. (Circ Arrhythm Electrophysiol. 2011;4:211-217.)
Key Words: radiofrequency ablation 䡲 cryoablation 䡲 cryoenergy 䡲 infants 䡲 neonates
L
arge registry data indicate that radiofrequency catheter
ablation procedures may be effectively and safely performed in children.1,2 However, infants and toddlers weighing
⬍15 kg have been identified as a subgroup at higher risk of
complications.3 Among the concerns raised are late tissue effects
related to lesion growth in immature myocardium.4 Indeed, Saul
et al5 noted that radiofrequency ablation lesions expand over
time in infant sheep, with multiple extensions of fibrous and
elastic tissue into surrounding normal myocardium. Clinically, a
few cases of sudden death were reported in infants after
radiofrequency catheter ablation, with expansive lesions confirmed by autopsy.6,7 It remains unknown whether cryoablation,
which involves mechanisms of cellular injury different from
thermal energy and produces distinct lesions with preserved
tissue ultrastructure, is associated with less propensity for lesion
expansion in immature hearts. Our objective, therefore, was to
characterize and compare the growth of lesions produced by
cryothermal and radiofrequency catheter ablation in infant hearts.
Editorial see p 123
Clinical Perspective on p 217
Methods
Study Design
A randomized, factorial design, summarized in Figure 1, was devised
to compare the growth rate of ablation lesions produced by radiofrequency versus cryothermal ablation in 32 infant Yucatan miniature swine 1 to 3 months of age, weighing ⬍10 kg. This animal
model was selected for its similarities to human neonates with regard
to degree of maturity of the cardiovascular system at birth and its
pattern of growth over time.8,9
The transcatheter energy modality, that is, radiofrequency or
cryoablation, and time of euthanasia, that is, acute or 1, 6, or 12
months, were randomly allocated. The unit of randomization was the
“cardiac chamber,” grouped into 4 categories: right atrium, left
atrium, right atrioventricular (AV) groove/right ventricle, and left
AV groove/left ventricle. Two ablation lesions were created in each
Received June 14, 2010; accepted December 20, 2010.
From the Electrophysiology Service and Research Center, Montreal Heart Institute, and the Biostatistics Service, Montreal Heart Institute Coordinating
Centre, Université de Montréal, Montreal, Canada.
Correspondence to Paul Khairy, MD, PhD, Montreal Heart Institute, 5000 Belanger St E, Montreal, QC, H1T 1C8, Canada. E-mail
[email protected]
© 2011 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org
211
DOI: 10.1161/CIRCEP.110.958082
212
Circ Arrhythm Electrophysiol
April 2011
Figure 1. Overview of study design. Time of euthanasia and energy modality for transcatheter ablation were randomly allocated. RA
denotes right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle; LAVG, left atrioventricular groove; and RAVG, right atrioventricular groove.
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right and left atrium, ventricle, and AV groove (posterior and lateral)
for a total of 12 lesions per animal. Although both cryothermal and
radiofrequency ablation may have been performed in any individual
minipig in accordance with the randomization scheme, the same
catheter was used for all lesions in a given cardiac chamber. To
minimize misclassification errors, AV groove lesions were performed with the same energy modality as the corresponding ventricles. The study was approved by the Montreal Heart Institute Animal
Care and Use Committee and conformed to the guiding principles of
the Canadian Council on Animal Care and Declaration of Helsinki.
Ablation Protocol
Acetylsalicylic acid (325 mg/d) was initiated 2 days before ablation and
continued until animal euthanization. The miniswine were anesthetized with pentobarbital sodium (25 to 30 mg/kg), intubated, and
ventilated with positive-pressure Harvard respirators. An intravenous
heparin bolus of 100 IU/kg was administered at the start of the
procedure, followed by hourly injections of 15 IU/kg.
Sheath introducers were positioned in the femoral vein. In adherence
to the protocol, a 7F cryocatheter (Freezor, Medtronic CryoCath LP,
Montreal, Canada) or 7F quadripolar radiofrequency catheter (Biosense
Webster, Inc, Diamond Bar, CA) with a 4-mm distal electrode tip was
positioned under fluoroscopic guidance. In all animals, the left side of
the heart was accessed via a patent foramen ovale. Surface and
intracardiac ECG recordings were displayed on a digitalized electrophysiology recording system (EP WorkMate System, St Jude Medical,
St Paul, MN) and stored on a multigigabyte hard drive and optical disk.
Each cryoapplication was maintained for 4 minutes, with a single
freeze-thaw cycle. Temperatures were displayed and recorded by a
CryoCath console with ⫾1°C accuracy over the range of ⫹40°C to
⫺80°C at a sampling rate of 10/s. Average and maximum cooling rates
and average and minimum temperatures were calculated using a
customized Matlab program. Radiofrequency ablations were maintained
for 60 seconds at 40 W with a target temperature of ⫹60°C. Maximum
impedance and maximum and mean temperatures and power were
displayed on the generator (EP Technologies Inc, San Jose, CA).
Morphometric Analyses
In accordance with the factorial design, animals were euthanized
immediately after the procedure (n⫽8) or at 1 month (n⫽8), 6
months (n⫽8), or 12 months (n⫽8) after ablation with a lethal
injection of pentobarbital. Heart and lungs were explanted, rinsed,
fixed in 10% formalin, and transferred to a pathology laboratory. All
personnel were blinded to the ablation modality. Representative
photographs of epicardial and endocardial surfaces were taken and
gross surface maximal lesion length and width measured. Tissue
blocks containing the entire ablation lesion with adhering tissue were
excised, dehydrated, and paraffin-embedded. Specimens were seri-
ally sectioned perpendicular to the endocardial surface in 1000-␮m
increments at a thickness of 6 ␮m with a motorized microtome
(Olympus No. 4060E) and stained with Masson trichrome. A
calibrated light microscope using Scion image 1.60 software for
CG-7 (Scion Corp, Frederick, MD) was used for morphometric
analyses to reconstruct ablation lesion dimensions. An ablation
lesion was considered transmural if any portion extended from the
endocardial surface all the way through the cardiac wall thickness.
Thrombus was defined as being present if its volume exceeded
0.1 mm3.
In a validation subanalysis, 15% of ablation lesions were randomly selected for independent morphometric analyses by 2 blinded
expert observers.
Statistical Analyses
Nonadjusted continuous variables are presented as mean⫾standard
deviation. Given that several ablation lesions were created in each
animal, analyses considered the nonindependent data structure.
Adjusted summary statistics are presented as estimated marginal
means with standard errors. Generalized estimating equations were
used to produce marginal regression models for cluster sampling data
by specifying link (ie, identity) and distribution (ie, normal) functions for continuous outcomes (ie, lesion depth, width, and volume).
First-order autoregressive [AR(1)], exchangeable, and unstructured
correlation structures were considered. The AR(1) correlation structure was retained since it was associated with the smallest quasilikelihood under independence model criterion. Cardiac chamber was
included as a covariate in models assessing changes in lesion
dimensions over time with radiofrequency versus cryoablation. For
comparisons of thrombus formation, a binomial distribution was
specified with a logit link and an exchangeable correlation structure.
Interobserver reliability was assessed by means of an intraclass correlation coefficient.10 Probability values ⬍0.05 were considered statistically significant. Statistical testing was performed using SAS software
Version 9.2 (SAS Institute, Cary, NC). The study was designed to
provide ⬎80% statistical power to detect an effect size (difference in
mean volume/common standard deviation of volume) of 0.7 at each
time point, with an overall significance level of 0.05.
Results
Ablation Lesion Identification and Settings
A total of 384 ablation lesions were systematically created in
right and left atria, right and left ventricles, and right and left
AV grooves of 32 Yucatan miniature swine weighing
8.8⫾1.2 kg at 63⫾13 days of age. A total of 311 (81.0%)
lesions were identified macroscopically and processed for
Khairy et al
Lesion Expansion With Radiofrequency Versus Cryoablation
213
Figure 2. Epicardial surface 1 year after
ablation. Gross appearance of ventricular
lesions 1 year after endocardial cryothermal (A) and radiofrequency (B) catheter
ablation are shown. Note the large, pale,
white lesions on the epicardial surface of
the left ventricles. In addition, a pearly
white transmural lesion produced in the
left atrium by radiofrequency energy may
be seen in panel B.
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histological analyses. Missing lesions were equally distributed between the two energy modalities (ie, cryothermal 37;
radiofrequency 36), with 24 (32.9%) delivered in atria, 14
(19.2%) in ventricles, and 35 (47.9%) at AV grooves. The
average temperature recorded during cryoablation was
⫺73.2⫾14.9°C, with a minimum temperature of
⫺79.8⫾3.4°C. All lesions were applied for 4 minutes. The
average temperature recorded during radiofrequency ablation
was 54.4⫾5.5°C, with an impedance of 112.7⫾16.5 ⍀, and
power of 26.3⫾3.4 W. The average duration of radiofrequency
applications was 59.2⫾7.4 seconds, with 8 of 64 (12.5%)
ventricular ablation lesions interrupted prematurely by 5 seconds
or more due to ventricular tachycardia or fibrillation. In contrast,
no ventricular arrhythmia was induced by cryoablation.
Ablation Lesion Characteristics
On qualitative microscopic analysis, acute cryothermal and
radiofrequency ablation lesions were hemorrhagic, with
prominent contraction band necrosis. Cryoablation lesions
were well delineated, with an endocardial surface that was
rarely disturbed. In contrast, radiofrequency ablation lesions
were characterized by disruption of the endothelial cell layer
and ragged edges less clearly demarcated from underlying
normal myocardium. Gross appearance of late lesions are shown
in Figure 2 and representative histological examples are portrayed in Figure 3. Except for increasing size, 1-, 6-, and
12-month lesions appeared similar, with normal myocardial cells
replaced by dense areas of fibrosis. Multiple extensions of
fibrous and elastic tissue appeared as early as one month with
both cryothermal and radiofrequency ablation.
Transmural lesions were noted in all locations at all stages
of maturity but were more common in the atria (70.1%) than
ventricles (38.8%) or AV grooves (36.6%) (overall,
P⬍0.0001). The proportion of transmural lesions was similar
between cryothermal and radiofrequency ablation (P⫽0.96).
Thrombus on the lesion surface was more frequently seen
Figure 3. Histological characteristics of
cryothermal and radiofrequency ablation
lesions. Typical histological characteristics
1 month (A) and 1 year (B) after radiofrequency ablation are shown. Lesions at 1
month (C) and 1 year (D) after cryothermal
ablation are shown. All displayed lesions
were created in the right ventricle, stained
with Masson trichrome, and magnified
16-fold for visual comparison. At 1 month,
thrombus is noted on the surface of the
radiofrequency (A) but not cryothermal (C)
ablation lesion. Twelve-month lesions are
devoid of surface thrombosis (B and D).
Multiple extensions of fibrous and elastic
tissue were observed as early as 1 month
after ablation. Note the much larger lesion
volumes at 12 months (B and D) compared with 1 month (A and C).
214
Circ Arrhythm Electrophysiol
Table.
April 2011
Lesion Dimensions According to Site of Ablation and Time of Euthanasia
Ablation Lesion Dimensions
Time of Euthanasia
Animal Weight, kg
Acute
9.0⫾1.7
Parameter
All
(n⫽311)
Atrium
(n⫽104)
Ventricle
(n⫽114)
AV Groove
(n⫽93)
Width, mm
5.1⫾0.4
5.4⫾0.8
4.6⫾0.4
5.0⫾0.6
Depth, mm
3.4⫾0.2
2.6⫾0.2
3.8⫾0.3
3.2⫾0.3
Volume, mm
89.9⫾13.1
68.3⫾13.7
105.2⫾16.1
78.9⫾19.1
Width, mm
5.4⫾0.5
5.6⫾0.5
4.9⫾0.3
4.8⫾0.6
Depth, mm
3.5⫾0.2
3.0⫾0.3
4.4⫾0.3
3.5⫾0.4
Volume, mm3
121.2⫾20.3
124.2⫾33.4
126.8⫾22.0
143.9⫾36.3
6.0⫾0.6
3
1 Month
6 Months
12 Months
18.3⫾1.7
44.5⫾10.1
62.8⫾31.2
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P value*
Width, mm
5.7⫾0.0.3
6.3⫾0.5
6.0⫾0.4
Depth, mm
4.9⫾0.3
3.8⫾0.5
5.9⫾0.5
4.5⫾0.7
Volume, mm3
162.1⫾23.7
166.7⫾46.4
168.6⫾20.1
148.5⫾53.3
Width, mm
6.5⫾0.4
7.1⫾0.6
6.4⫾0.5
6.4⫾1.5
Depth, mm
5.6⫾0.5
4.6⫾0.6
6.3⫾1.1
6.2⫾0.6
Volume, mm3
232.5⫾24.2
226.9⫾37.7
276.7⫾34.3
118.3⫾28.9
Width, mm
...
0.058
0.49
0.55
Depth, mm
...
0.86
0.18
0.50
...
0.44
0.57
0.69
3
Volume, mm
Estimated marginal means derived from generalized estimating equations are presented for all ablation lesion dimensions, along
with standard errors.
*P values compare changes in lesion dimensions over time with cryoablation versus radiofrequency ablation and are derived from
multivariate generalized estimating equations regression models (see Statistical Analyses). Pooled analyses of all lesions are not
provided, given that growth curves were heterogeneous with respect to chamber of ablation.
with radiofrequency than cryothermal ablation (27.3% versus
13.6%, P⫽0.006). It was predominantly observed in the acute
setting (ie, 73.3% versus 26.8% with radiofrequency versus
cryothermal ablation, P⬍0.0001) and detected on only 1
radiofrequency and 1 cryoablation lesion at 6 months. All
12-month lesions were devoid of thrombus.
Ablation Lesion Dimensions
The minipigs increased in weight from 8.8⫾1.2 kg at baseline
to 62.8⫾31.2 kg at 12 months. The intraclass correlation
coefficient for morphometric analyses was 0.991
(P⬍0.0001). Dimensions of ablation lesions are summarized
in the Table according to time of euthanasia and chamber of
ablation. Estimated marginal mean volumes of acute cryoablation versus radiofrequency ablation lesions were
86.4⫾12.6 mm3 versus 100.9⫾15.5 mm3, respectively
(P⫽0.26). Maximum acute lesion depths were 3.9⫾0.3 mm
with cryoablation and 3.2⫾0.1 mm with radiofrequency
energy (P⫽0.035). Corresponding maximum widths were
4.9⫾0.7 mm and 5.4⫾0.2 mm, respectively (P⫽0.45). Acute
ventricular lesion volumes in atria, AV grooves, and ventricles were 68.3⫾13.7 mm3, 78.9⫾19.1 mm3, and
105.2⫾16.1 mm3, respectively, with a statistically significant
difference between atria and ventricles (P⫽0.007). Lesion
volumes were similar in right versus left-sided cardiac chambers (P⫽0.90).
Enlargement of Ablation Lesions
Figure 4 portrays the rate of enlargement of lesions produced
by radiofrequency and cryothermal energy according to site
of ablation. On morphometric analyses, no differences in the
rate of growth of ablation lesions were noted between the 2
energy modalities in atria (P⫽0.44), ventricles (P⫽0.57), or
AV grooves (P⫽0.69). As summarized in the Table, increases in lesion depth and width were likewise similar with
radiofrequency and cryothermal ablation. Over a 12-month
period, ablation lesion volumes increased 3.3-fold in atria
(95% confidence interval [CI], 2.3 to 4.3; P⫽0.001) and
2.2-fold in ventricles (95% CI, 1.4 to 3.0; P⬍0.004), with the
difference between the 2 chambers being nonsignificant
(P⫽0.22). Whereas the depth of AV groove lesions increased
over time (1.9-fold; 95% CI, 1.5 to 2.3; P⬍0.0001), lesion
volumes did not enlarge significantly (1.5-fold; 95% CI, 0.4
to 2.6; P⫽0.45).
Discussion
Although radiofrequency catheter ablation is occasionally
indicated in infants and small children, the increased rate and
severity of complications have led some to recommend
reserving these interventions for dire circumstances.3,6,11–15 In
a series of 18 radiofrequency ablation procedures in children
weighing ⬍15 kg, complications included pericardial effusion, mitral regurgitation, and myocardial infarction.16 These
appeared to be related to the dose of radiofrequency energy
received, as indexed by body size. Substantial late tissue
effects have occasionally been observed in the young, with
rare cases of sudden death.6,7 Autopsies revealed myocardial
cavitation at the presumed site of ablation, with marked lesion
expansion.6,7
Such observations prompted Saul et al5 to systematically
assess acute and late effects of radiofrequency lesion production in immature myocardium. Under fluoroscopic guidance,
Khairy et al
Lesion Expansion With Radiofrequency Versus Cryoablation
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Figure 4. Growth of ablation lesions in atria, ventricles, and AV
grooves with cryothermal versus radiofrequency energy. Ablation lesion volumes produced by cryothermal (blue) and radiofrequency (red) energy in atria (A), ventricles (B), and atrioventricular grooves (C) are depicted by straight lines with
surrounding 95% CIs, according to time of euthanasia. No significant differences between cryothermal and radiofrequency
energy were observed. Note that lesion volumes at the AV
grooves did not increase significantly over time. *Probability values are derived from generalized estimating equations analyses
that include the time interval between ablation and animal
euthanasia, energy modality, and first-order interaction between
time and energy modality.
radiofrequency ablation lesions were created in all 4 cardiac
chambers of 19 infant sheep (10.9⫾1.4 kg). Lesion sizes and
histological characteristics were assessed acutely (n⫽5), at 1
month (n⫽5), and at 8.5 months (n⫽9). Whereas Saul et al
primarily focused on lesion width and depth, we further
215
extended these findings by performing detailed histological
3-dimensional morphometric analyses of lesion volume. Such
an approach overcomes limitations of formula-based estimates (eg, prolate ellipsoid)17 and yields highly consistent
results.18,19 Using this methodology, we confirmed the observation by Saul et al that radiofrequency ablation in immature
myocardium results in substantial enlargement of atrial and
ventricular lesions but not AV groove lesions over time.
Although underlying mechanisms remain unknown, it was
speculated that expansion of radiofrequency ablation lesions
may be driven in part by the serrated bordering zones18,20,21
that produce multiple extensions of fibrous and elastic tissue
into surrounding normal myocardium.5,22
The main focus of the current study was to determine
whether cryoablation in immature myocardium would result
in a comparable degree of lesion enlargement to radiofrequency ablation. Because the 2 energy modalities produce
cellular effects through different mechanisms and result in
lesions that are histologically distinct, we speculated that
lesion expansion in immature myocardium would likewise
differ. By virtue of the fact that cryolesions are more
homogeneous, with clearer and smoother demarcations from
underlying normal myocardium,20,23 and that ultrastructural
tissue integrity is maintained,24 with lesser propensity to
rupture or form aneurysms,25,26 we hypothesized that cryolesions would enlarge to a lesser degree. Our hypothesis was
tested using a rigorous randomized factorial design with a
previously validated end point (intraclass correlation coefficient of 0.991) that is robust to irregularities in lesion
morphology. Moreover, because the unit of randomization
was the cardiac chamber as opposed to the animal, the study
design allowed for coexisting radiofrequency and cryoablation lesions within the same minipig. This approach was
combined with generalized estimating equations analyses to
isolate the impact of energy modality and limit animalspecific outlier effects.
Acute ablation lesion characteristics observed, proportion
of missing lesions, and greater thrombogenic potential with
radiofrequency energy are consistent with prior reports.18,19,27
Acute lesion sizes and the extent of variability obtained by
4-mm electrode-tip radiofrequency and cryothermal ablation
catheters, with cryoablation producing nonsignificantly
smaller lesion volumes, are likewise compatible with prior
observations in mature animals.18,19 It is worth noting that
although the study was powered to compare expansion rates
of ablation lesions according to energy modality, analyses
that further divide lesions into multiple subgroups (eg, by
cardiac chamber and time of euthanasia) are limited by
smaller sample sizes.
In adult animals, cryoablation lesions have not been noted
to expand over time and are considered mature by 7 days,
with sharp borders, dense areas of fibrotic tissue, and contraction band necrosis.18,19 The postablation healing response
is somewhat slower with radiofrequency energy, as replacement fibrosis is confined to the outer margin of lesions at 7
days, with lingering intralesional hemorrhage.18,19 Radiofrequency ablation lesions become densely fibrotic by 1
month.28 We had speculated that differences in the pathophysiology of acute injury and healing processes associated
216
Circ Arrhythm Electrophysiol
April 2011
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with cryothermal and radiofrequency ablation may produce
different effects on immature myocardium. Contrary to our
hypothesis, the enlargement of cryolesions was similar to
radiofrequency lesions in all cardiac chambers. These results
suggest that ablation lesion enlargement in immature atrial
and ventricular myocardium is independent of the energy
modality by which they were produced.
It may be speculated that lesion growth is predominantly
determined by enlargement of the fibrous core that is common to radiofrequency and cryothermal lesions. Unlike fetal
wound healing, which is characterized by absence of scar,
transforming growth factor-␤1 is a ubiquitous cytokine with
potent postnatal fibrogenic effects.29 Indeed, neonatal fibroblasts express particularly high levels of latent transforming
growth factor-␤1 and insulin-like growth factor binding
protein-3, with upregulation of connective tissue growth
factor and collagen type I.30,31 In a newborn mouse model,
both connective tissue growth factor and transforming growth
factor-␤1 were strikingly upregulated 1 week after induced
myocardial infarction in fibroblasts and within the thin layer
of surrounding surviving myocytes.32 The 2 ligands colocalized with fibronectin and were clearly related to the development of fibrosis.32 This rapid fibrogenic response is compatible with our observation of multiple extensions of
fibroelastic tissue as early as 1 month after ablation.
Conclusion
As the immature myocardium grows, atrial and ventricular
lesions produced by cryothermal and radiofrequency ablation
enlarge to a similar degree, refuting the notion that cryoablation should be favored on the basis of lesion expansion. In
contrast, AV groove lesion volumes do not increase significantly with either energy modality. Further studies are required to elucidate the pathogenesis of ablation lesion growth
in immature myocardium, identify potential therapeutic targets to limit lesion expansion, and assess the efficacy of
preventive approaches.
Acknowledgments
We thank Dominique Lauzier and Marie-Élaine Clavet-Lanthier for
expert technical assistance.
Sources of Funding
The study was supported by the Montreal Heart Institute Research
Foundation (Bal du Coeur) and a Canada Research Chair in
Electrophysiology and Adult Congenital Heart Disease (Dr Khairy).
Disclosures
Dr Dubuc is a consultant for Medtronic CryoCath LP. Dr Roy was
chairman of a clinical adjudicating events committee for a trial
sponsored by Medtronic CryoCath LP (STOP-AF).
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CLINICAL PERSPECTIVE
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Catheter ablation in infants and small children, though once reserved for life-threatening or drug-refractory arrhythmias,
is increasingly performed. However, radiofrequency ablation lesions may expand considerably over time, and occasionally
result in sudden death. Cryoablation has an attractive safety profile and involves mechansims of tissue injury distinct from
radiofrequency ablation. It was unknown whether cryoablation is associated with a similar propensity for lesion expansion
in immature hearts. We therefore randomly assigned 32 infant miniature swine (63⫾13 days of age; 8.8⫾1.2 kg) to catheter
ablation by radiofrequency or cryothermal energy. A total of 384 ablation lesions were created in all cardiac chambers and
atrioventricular grooves. Animals were euthanized acutely or at 1, 6, or 12 months, according to the randomization scheme.
Atrial and ventricular ablation lesion volumes produced by cryothermal energy increased 2- to 3-fold within a year, in a
manner similar to radiofrequency ablation. In contrast, atrioventricular groove lesion volumes did not increase significantly
with either energy modality. These results suggest that lesion enlargement in immature myocardium is independent of the
type of energy used for ablation and may be predominantly determined by growth of the fibrous core. Late tissue effects,
therefore, remain a real concern with either energy modality and should be considered when balancing risks and benefits
of catheter ablation in infants and small children.
Enlargement of Catheter Ablation Lesions in Infant Hearts With Cryothermal Versus
Radiofrequency Energy: An Animal Study
Paul Khairy, Peter G. Guerra, Lena Rivard, Jean-François Tanguay, Evelyn Landry,
Marie-Claude Guertin, Laurent Macle, Bernard Thibault, Jean-Claude Tardif, Mario Talajic,
Denis Roy and Marc Dubuc
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Circ Arrhythm Electrophysiol. 2011;4:211-217; originally published online January 21, 2011;
doi: 10.1161/CIRCEP.110.958082
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