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Paradigms for the Ablation of Persistent Atrial Fibrillation
Atul Verma, MD
I
t has been more than 8 years since the first
patient was enrolled in the pivotal TTOP-AF (Tai-
lored Treatment of Persistent Atrial Fibrillation)
study,1 which initially evaluated the performance of a
multipolar, phased radiofrequency (RF) system (Ablation Frontiers, Medtronic, Inc.). In brief, phase-shifted
energy delivered between adjacent catheter electrodes
(bipolar) and return electrodes (unipolar) allowed for
creation of long contiguous lesions. The efficacy of the
technology was quite promising showing that nearly
56% of patients experienced substantial improvement
in AF burden at 6 months.
At least for now, it should be noted that ablation is
for symptomatic improvement only; there is no evidence to date of a mortality benefit nor other beneficial
clinical effect (such as any reduction in stroke risk).
But for symptomatic improvement and QOL, ablation
can be beneficial.
In smaller studies, the technology also achieved
outcomes comparable with traditional, single-point
RF technology while significantly reducing procedural
time. Consequently, discussion during the U.S. Food
and Drug Administration (FDA) panel hearing in 2011
showed unanimity that the technology was effective in
the treatment of persistent AF. However, due to safety
concerns, the technology was not approved; highly
concerning in particular: the peri-procedural stroke rate
in TTOP-AF was 2.9%. There were also studies showing that the incidence of asymptomatic cerebral emboli
post-ablation was significantly higher with phaseshifted RF technology compared with open-irrigated,
single-point RF and cryoablation.
Face it: persistent AF is a challenge. Percutaneous catheter ablation remains an
effective treatment for paroxysmal AF, particularly in patients
refractory to antiarrhythmic
medications. As Atul Verma,
MD, Southlake Regional Health
Centre, Newmarket, Ontario,
To listen to the
noted,2 most triggers for paroxinterview with Atul
ysmal AF come from the pulmoVerma, MD, visit
the CSWN YouTube
nary veins, so ablation involves
channel or scan the
creating circumferential lesions
QR code. Interview
around the veins to electrically
conducted by Peter
A. McCullough, MD,
isolate them from the rest of the
MPH.
left atrium. Catheter ablation for
persistent AF is more difficult
and is associated with less favorable outcomes.
To improve outcomes, ablation targeting the substrate that
maintains fibrillation (i.e., sub-
22
CardioSource WorldNews: Interventions
strate modification) is often added (per the guidelines)
to pulmonary vein isolation (PVI). Recently Dr. Verma
and colleagues published the results of STAR AF II
(the Substrate and Trigger Ablation for Reduction of
Atrial Fibrillation Trial Part II).2 This randomized trial
compared three strategies of ablation for persistent AF:
• ablation with pulmonary-vein isolation (PVI)
alone (n = 67);
• PVI plus ablation of electrograms showing complex fractionated activity (n = 263); and
• PVI plus additional linear ablation across the left
atrial roof and mitral valve isthmus (n = 259).
As you can imagine, procedure time was significantly
shorter for PVI alone compared to the other two
procedures (p < 0.001). What did you get for the extra
procedural time? After 18 months, 59% of patients
assigned to PVI alone were free from recurrent AF
versus 49% of patients assigned to PVI plus complex
electrogram ablation, and 46% of patients assigned
to PVI plus linear ablation (p = 0.15). So, not much.
There were also no significant differences among
the three groups for secondary endpoints, including
freed om from AF after two ablation procedures and
freedom from any atrial arrhythmia.
Serious adverse events included three instances
of cardiac tamponade and three instances of stroke
or transient ischemic attack. In one patient assigned
to isolation plus electrograms, a procedure-related
atrioesophageal fistula developed that was complicated
by stroke; this was successfully treated by esophageal
stenting, but the patient died 3 months later of aspiration pneumonia.
The only complications seen with PVI alone: two
patients had an access site hematoma; one patient
experienced a skin burn; and one patient suffered one
of the three tamponades. The other 30 adverse events
were spread across the other two groups.
GUIDELINES NOT SUPPORTED
Verma and colleagues noted that their findings are
not in accordance with current guideline recommendation that patients with persistent AF who undergo
PVI should have additional substrate ablation to
improve outcome. The good news: PVI alone can
achieve a successful outcome in about half of patients with persistent AF.
Why the guidelines-endorsed approach did not add
benefit in STAR AF II is unclear. Verma et al. hypothesize that more extensive ablation may cause new,
iatrogenic areas of arrhythmogenesis where tissue is
incompletely ablated or linear block is not achieved.
Perhaps neither complex electrograms nor lines are the
correct supplemental targets for ablation. More selective targets may be needed to better characterize an
individual patient’s specific arrhythmic substrate.
Perhaps the lack of benefit seen with performing
additional, and possibly unnecessary, ablation increases risk. After all, procedure time in STAR AF II
was longer by almost an hour in the additional-ablation
groups and was associated with increased exposure to
fluoroscopy for the patient and the operator.
As Dr. Verma put it in a recent editorial comment:
While data offer good news for patients and operators,
the existing data are still derived largely from nonrandomized, retrospective, or limited studies of few
patients.3 As to how newer technologies will fit into
our armamentarium of catheters for AF ablation, Dr.
Verma wrote, “We need proper prospective, comparative, randomized trials.” Anything less than that, he
added, will only keep us moving in circles. ■
REFERENCES
1. Hummel J, Michaud G, Hoyt R, et al; TTOP-AF Investigators. Heart Rhythm. 2014;11:202-9.
2. Verma A, Jiang CY, Betts TR, et al. N Engl J Med.
2015;372:1812-22.
3. Verma A. Europace. 2016 Mar 21. pii:euw004 [Epub ahead
of print].
4. De Greef Y, Dekker L, Boersma L, et al. Europace. 2016 Jan
29. pii:euv385 [Epub ahead of print].
Editor’s note: Atul Verma, MD, is an Associate Editor of
JACC Clinical Electrophysiology. Recently, he and the
other JACC EP editors participated in a JACC Grand
Rounds: Highlights of HRS.16. To view this program,
featuring the best of the 2016 Heart Rhythm Society
meeting, follow this link: jaccgrandrounds.org/
Take-aways
• Catheter ablation is less successful for
persistent AF than for paroxysmal AF.
• Despite guideline recommendations, a study
evaluating three approaches to radiofrequency
ablation for patients with persistent AF found
no reduction in the rate of recurrent AF when
either linear ablation or ablation of complex
fractionated electrograms was performed in
addition to pulmonary vein isolation.
July/August 2016