<div>AMEN and ALARA – Remembering the dangers of the (new) technology of
lesion formation.</div><div>Mark E Alexander, MD</div><div>Edward T O’leary, MD</div><div>Arrhythmia Service</div><div>Department of Cardiology</div><div>Boston Children’s Hospital</div><div>Department of Pediatrics, Harvard Medical School</div><div>Boston, MA</div><div>1284 words</div><div>6 References</div><div>No external funding</div><div>Conflict of Interest:</div><div>Dr. O’leary receives research funding from Abbott Cardiovascular</div><div>Corresponding Author</div><div>Mark E Alexander, MD</div><div>Mark.alexander@cardio.chboston.org</div><div>617-355-6328</div><div>Fax: 617-730-0000</div><div>Catheter ablation has changed the natural history of children with
supraventricular tachycardia. Those of us over 60 years of age remember
the burden associated with recurrent arrhythmias, the emergency room
visits (which before 1989 required some drug not named adenosine), the
chronic drug therapy, digoxin toxicity, and maybe even having to give
quinidine. For older children and adolescents with recurrent SVT,
catheter ablation has become the therapy of choice.</div><div>Catheter ablation is both effective and safe, particularly for localized
and easily characterized arrhythmia mechanisms. The high quality
prospective observational PAPCA trial and the parallel European study
demonstrated virtually no late myocardial dysfunction and very low
incidence of atrioventricular (AV) block. Success rates are now
routinely &gt;95% for AV reciprocating mechanisms or AV nodal
re-entrant tachycardia. Those success rates have probably incrementally
improved over the last decade and build on a base of long-term success
and safety. That safety profile has settled so that patients over
~15 kg are reasonable candidates for elective ablation,
with ablation in younger patients clearly feasible but reserved for
those with substantial hemodynamic and/or drug morbidity.</div><div>Operators now have options for catheters with irrigated tips and contact
force sensors for radiofrequency (RF) ablation, and larger tipped
cryocatheters when that technology is preferred. The combination of
contact force sensors and irrigated tip ablation has clearly contributed
to increased ablation success in atrial flutter, atrial fibrillation,
and ventricular tachycardia. Success rates with more localized
mechanisms like accessory pathways have been sufficiently high for a
sufficiently long period that demonstrating superiority of any approach
is a challenge. This background is critical for viewing the present
study by Backhoff and colleagues in this issue of the journal, where
they investigate the use of a contact force ablation catheter in a
careful animal experiment. They used 15-22 kg piglets which is a
plausible model for younger children. The underlying hypothesis is quite
reasonable: that elevated contact force results in a larger lesion size
and thereby increases the frequency of coronary injury. Each animal had
a sequence of lesions on the atrial and ventricular walls and the
tricuspid and mitral annuli. They targeted either a low contact force of
10-20 g (which to explicitly state represents routine clinical care in
humans) or a high contact force of 40-60 g and delivered 30 second
lesions with a power ceiling of 30 W and temperature ceiling of 65 C. A
total of 172 lesions were assessed with acute coronary angiography
followed by subgroups with postmortem analysis at 48 hours and 6 months.
Each targeted location had one RF application at the target contact
force.</div><div>There is, I think, no surprise that ventricular myocardial lesions were
larger than AV groove lesions which were larger than atrial myocardial
lesions.  Similarly, there was some lesion contraction with lesion size
being larger at 48 hours than at 6 months for those placed on the AV
groove and in the ventricular myocardium (though not the atrial
lesions). Backhoff and his colleagues in this research group in
Gottingen, Germany have been careful about documenting potential risk of
coronary injury with both acute clinical coronary angiography and an
animal model using cryoablation.  Extending the animal model to a
contact force catheter demonstrated a frequency of coronary obstruction
in 5% of all observed lesions on the day of the procedure, decreasing
to 2.5% by 48 hours and 1.4% by 6 months. Fortunately, there was
excellent coronary flow in the affected coronaries at each time
point. They note a parallel but somewhat higher incidence of transmural
extension of these lesions. These data provide the usual anxiety that we
have about ablation on the AV groove, however the optimist can take
comfort in the larger clinical experiences and their confidence that
they are (hopefully) using a “low” contact force of 10-20 g.</div><div>When the relationship between contact force and lesion size is examined
in detail, the limitations of their hypothesis become readily apparent.
The only lesion set where high contact force was associated with larger
lesions was that at the AV groove examined at 6 months. Here, both the
lesion volume (~6 mm diameter hemisphere) and percentage
of transmural lesions were higher in high contact force than the low
contact force lesions (~5 mm diameter hemisphere). There
were not significant differences in lesion volume or transmural
extension for atrial lesions or ventricular lesions. In some of those
lesion sets the low contact force set had insignificantly higher
volumes. In figure 2 they present scatter plots of lesion volume and the
force-time product, with the surprising conclusion that there is no
relationship between those two values. Indeed, on pathology only about
90% of the lesions could be identified, implying that 10% of the
lesions they placed did not result in tissue damage. Lesion size ranged
from 4.2 mm diameter to nearly 8 mm diameter hemispheres. There are
obviously other metrics that could be correlated with lesion size with
time-temperature integrals, impedance drops, and loss of electrogram
size as obvious favorites; those are not presented.</div><div>There are several potential ways to digest these data. The initial
hypothesis that higher contact force would reliably produce larger
lesions is at best incompletely confirmed by the results. The
statistical purest will focus on the weakness of that association with
lesion volume and assert that that finding was the result of not
correcting for multiple measures. They may say that this is underpowered
and “more studies are needed ” or even that the data do not support
the authors’ hypothesis.  To me, the challenges of this analysis are
actually the more important signal. Regardless of tip contact force,
lesion size could range from ~4-8.5mm in diameter  with
variable development of either transmural extension or lesion
contraction. Even in a relatively controlled environment with careful
lesion characterization, ~10% of applications did not
result in a pathologically visible lesion (so the size was really 0-8mm
diameter!). Clinically, we look for an acute change in physiology to
decide if a lesion is effective and then may place some additional
“consolidation” or “insurance” lesions if that physiology remains
favorable—or move to a different location if the pathway returns. Most
of us, I believe, are unlikely to accept a single 30 second lesion on
the AV groove. We do not have the luxury of seeing what these
applications look like 2 days or 6 months later. What happens with the
second 30 second application? What happens with further repeat
applications?  What is the catheter tip force when a catheter without
that technology is used?</div><div>Each technology that assists in catheter ablation inserts not only
increased precision, but also an increased “sense” of precision. The
variables that we observe during these procedures are important and
numerous, but each has a confidence interval.  Some of the damage we
create is silent and subclinical (at least for now). Analyses like these
help refine what we know, which is that 6 months after a RF ablation in
a 15 kg piglet, 1-2% of single lesions will produce subclinical
coronary obstruction which would not have been identified without
coronary angiography.</div><div>For fluoroscopy, a safety principle of As Low As Reasonably Achievable
(ALARA) is the standard. Given both the uncertainty of lesion size and
the clear potential of at least subclinical coronary injury that this
group has demonstrated in both clinical and animal settings, combined
with the low but real incidence of catastrophic coronary injury, maybe a
similar principle is appropriate with ablation along the AV groove. At
the same time ,the goal of each iteration of catheter technology is to
assure that we give As Much as Effectively Needed (AMEN). Data like
these, with low but real and potentially silent risks, remind us that
those are goals we need to always to balance.</div>