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What is the Latest on Catheter Ablation of Atrial
Fibrillation?
Jason G. Andrade MD, Marc W. Deyell MD MSc, Laurent Macle MD
DOI: 10.22374/cjgim.v13iSP1.308
About the Authors
Jason Andrade and Laurent Macle are with the Electrophysiology Service at the Montreal Heart Institute and the Department of Medicine,
Université de Montréal, Montreal, Canada. Marc Deyell with the Heart Rhythm Services, Department of Medicine, The University of
British Columbia, British Columbia, Canada.
Correspondence may be directed to: lmacle@mac.com
Atrial fibrillation (AF) is the most common sustained cardiac
arrhythmia observed in clinical practice, affecting 1–2% of the
general population. AF is associated with reductions in quality
of life, functional status, cardiac performance, and survival.
1
In
addition, AF accounts for 1.0–2.7% of total annual healthcare
expenditures, with a sizeable proportion of these expenses
attributed to direct costs associated with emergency department
visits and acute care hospitalization.
2–5
The contemporary management of AF is centred on symptomatic
improvement, reduction in healthcare utilization, and reduction
in AF-associated morbidity and mortality (in particular the
prevention of stroke or systemic thromboembolism).
6
While
ventricular rate control can be effective, many patients remain
symptomatic despite optimal rate control. For these patients,
restoration and maintenance of sinus rhythm can alleviate
symptoms, and improve quality of life. Oral antiarrhythmic
drug (AAD) therapy, which remains the “first-line” therapy
for the maintenance of sinus rhythm, has only modest efficacy
at maintaining sinus rhythm over the long term and can be
associated with significant side-effects such as pro-arrhythmia,
heart failure, and organ toxicity.
7–12
For many patients, catheter ablation offers an alternative for
maintaining sinus rhythm when AADs have been ineffective or
cannot be tolerated. While catheter ablation has not been proven
to improve mortality, it has been shown to be universally superior
to AADs for the maintenance of sinus rhythm (AF elimination
in 66–89% with catheter ablation vs. 9–58% with AAD). In
addition, catheter ablation significantly improves symptoms,
exercise capacity, and quality of life.
13–23
The focus of this article will be a brief review of the history
of AF ablation, followed by a discussion of four areas where
significant recent developments have occurred.
Evolution of Current Ablation Strategies and
Techniques
Up until the mid to late 1980s the “multiple wavelet hypothesis”
was the dominant mechanistic theory of AF pathophysiology.
This theory postulated that AF results from the presence of
multiple independent coexisting wavelets that are occurring
simultaneously and propagating randomly throughout the atria.
This hypothesis postulated that AF could be initiated and then
perpetuated indefinitely as long as the atrium had a sufficient
area with adequately short refractory periods. As such, the early
surgical and percutaneous interventions aimed to decrease
arrhythmia perpetuation by compartmentalizing the atrium into
smaller regions. It was thought that reducing the excitable mass
of atrial tissue would render the atria incapable of sustaining
the critical number of circulating wavelets. The approach was
associated with only moderate success.
In the late 1990s Haïssaguerre and colleagues demonstrated
that AF was a triggered arrhythmia initiated by rapidly repetitive
discharges predominantly originating from the pulmonary veins
(PVs). This led to the development of percutaneous procedures
designed to electrically isolate the PV from the left atrium. Over
the past 20 years the technique of PV isolation (PVI) has evolved
significantly from focal ablation of discrete triggers within the
PV, to circumferential ablation of the left atrial myocardium
outside of the tubular veins with a goal of large circumferential
Canadian Journal of General Internal Medicine
4 Volume 13, Special Issue 1, 2018
Atrial Fibrillation Special Issue
electrical PVI (i.e., electrical conduction block into and out of the
PVs). This contemporary approach not only targets the initiating
triggers of AF (the PVs) but also the mass of electrically active
LA tissue capable of perpetuating AF (Figure 1).
Unfortunately, although the results of catheter ablation are
unequivocally superior to antiarrhythmic drug therapy, they are
not perfect. It can be anticipated that only approximately 70%
of paroxysmal AF patients will remain arrhythmia- and AAD-
free after a single ablation procedure. For persistent AF patients
the progressive pathoanatomical changes in the atria result in
a further reduced procedural efficacy (50–60% vs. 66–89% in
paroxysmal AF), but additional ablation strategies targeting the
substrate outside the PVs (linear ablation or ablation of complex
atrial fractionated electrograms) are not superior to PVI alone.
24
Therefore, PVI remains the cornerstone of catheter ablation for
paroxysmal and persistent AF.
25
However, it is important to realize that even in the face of
arrhythmia recurrence a clinical improvement can be obtained.
Recent studies have suggested that complete elimination of AF
may not be necessary, and that significant clinical benefit can
be obtained if the overall arrhythmia burden (i.e. time in AF) is
reduced. For example, a recent analysis from the CASTLE-AF trial
demonstrated that a 50% reduction in AF burden was associated
with a significant reduction in the risk of death (HR0.30), or
heart failure hospitalization (HR 0.43). Therefore, although the
arrhythmia might not be considered “cured” in all patients, a
significant proportion of patients derive meaningful clinical benefit.
Novel Technologies to Ensure Durable Pulmonary
VeinIsolation
While electrical PVI may be achieved acutely, the creation of
durable scar around the PVs with a percutaneous procedure is
challenging. With time, inadequate ablation leads to recovery
of electrical conduction between the PV and LA, which may
trigger recurrent arrhythmia episodes. In this regard several
novel ablation technologies have been designed in an effort to
improve ablation lesion creation.
Contact Force Sensing Catheters
Contact force (CF) sensing is a newly developed technology
embedded within the radiofrequency ablation catheter that allows
for the real-time estimation of the contact between the tip of the
catheter and the target myocardium. Durable lesion formation in
the atrium requires adequate catheter electrode-tissue contact.
Insufficient tissue contact can result in edema with only transient loss
of conduction. Available data suggests that incorporating real-time
CF assessment into the ablation procedure results in a reduction
in procedure time, ablation time, and total energy delivery.
26,27
Recent studies suggested improved arrhythmia outcomes when
the procedure was performed with adequate CF parameters (84%
one-year freedom from AF in the 47% of patients in whom ablation
was in the target range ≥80% of the time in SMART-AF, and 76%
one-year freedom from AF in the 57% of patients in whom ≥90%
of the lesions were >10g in TOCCASTAR).
28,29
Balloon-Based Technologies
While focal point-by-point radiofrequency catheter ablation has
shown considerable success, the procedure is time-consuming and
dependent on operator competency.
30
In response considerable
effort has been directed towards the development of technologies
that are less reliant on operator dexterity. The most mature of
these balloon-based technologies is the Cryoballoon (Medtronic,
Minneapolis, MN), a purpose-built ablation catheter specifically
designed for PVI. Instead of the “heat” utilized with radiofrequency
ablation, the cryoballoon employs freezing inside the balloon
to destroy the atrial tissue. When compared to radiofrequency
cryothermal energy offers several potential advantages, including
improved catheter stability (due to tissue adherence at freezing
temperatures), minimal endocardial surface disruption, reduced
thrombogenicity, and preserved ultrastructural tissue integrity
leading to a lower perforation risk.
31
Balloon-based technologies
Figure 1. Example of AF ablation with point-by-point contact force radiofrequency
(bottom left) and cryoballoon ablation (bottom right).
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 5
Andrade et al.
continue to evolve and recent studies have demonstrated
improved arrhythmia-free survival with the second-generation
cryoballoon compared to the first generation cryoballoon (OR
of arrhythmia recurrence 0.34 [0.26–0.45]; 10 studies, 2310
patients).
32,33
While these outcomes are comparable to standard
radiofrequency ablation,
34,35
ongoing studies are evaluating the
effectiveness of 2nd generation cryoballoon ablation compared
to CF sensing radiofrequency ablation.
36
Other balloon-based technologies include: (1) the HeartLight
laser balloon (CardioFocus, Marlborough, MA), which is an
endoscopic laser ablation catheter that allows direct visualization
of the endocardial surface of the PV during infrared light energy
ablation; (2) The multi-electrode Helios radiofrequency balloon
(Biosense); and (3) The Apama radiofrequency Balloon (Boston
Scientific, Marlborough, USA). Each of these technologies have
recently published encouraging short-term safety and efficacy
outcomes, with large randomized multicenter studies ongoing.
Ablation as a First-Line Treatment
The ideal management of patients with newly diagnosed
symptomatic AF remains unknown. Current practice guidelines
recommend a trial of antiarrhythmic drugs prior to considering
an invasive ablation procedure. However, the universal superiority
of ablation over antiarrhythmic drug therapy suggests that
performing catheter ablation earlier may offer an opportunity not
only for better symptom control but also to halt the progressive
pathophysiological and anatomical changes associated with AF.
37
So far the evidence supporting “first-line” catheter ablation (i.e.,
as an initial therapy prior to AAD) is promising, but far from
definitive. The MANTRA-PAF Study and the RAAFT studies
randomized patients to either first-line ablation or first-line
AADs.
14,38,39
Despite disparate ablation techniques, these studies
collectively demonstrated an improved freedom from recurrent
arrhythmia (37% reduction in AF recurrence vs. AAD therapy),
an improved freedom from symptomatic AF (43% reduction
in symptomatic AF vs. AAD therapy), and a reduction in the
overall AF burden (50% reduction over AAD therapy). While
the results of these studies suggest that ablation is more effective
than AAD therapy as first-line treatment, a significant proportion
of patients in the intervention group experienced arrhythmia
recurrence. Thus, the issue of first-line ablation remains an open
question, where further research is required before first-line
catheter ablation can be considered routine for most patients
with symptomatic paroxysmal AF.
Ablation in Patients with Heart Failure
AF and heart failure (HF) are global cardiovascular epidemics.
These conditions frequently coexist, and are both increasing in
prevalence.
40,41
AF is an independent predictor of progression,
hospitalization and death in the HF population.
42–46
While
restoring and maintaining sinus rhythm may be a therapeutic
target to improve outcomes, large randomized controlled trials
of antiarrhythmic drugs (AAD) have failed to support this
hypothesis.
47–51
It is postulated that the attenuated benefit observed
with AADs therapy is related to cardiac and non-cardiac toxicities
(e.g., pro-arrhythmia, conduction block, negative inotropy), and
ablation may be a more efficacious means to improve outcomes.
To date seven randomized trials have been performed, in
addition to an observational meta-analysis, and an observational
multi-centre cohort study. Collectively these studies have
demonstrated a single procedure success (e.g., elimination of any
AF episodes >30 seconds) in the range of 40–69%, with multiple
procedures improving the success up to 88%. Beyond arrhythmia
recurrence, catheter ablation of AF in HF patients with LV systolic
dysfunction appears to be associated with improvement in left
ventricular ejection fraction (LVEF improvement of 4.5–18%),
exercise performance (VO2 max improvement of 3 mL/kg/min
vs. comparator, and 6-minute walk improvement of 20–70 meters
from baseline), and quality of life (33% average improvement in
Minnesota Living with HF Questionnaire score).
52–58
However, a truer measure of the utility of catheter ablation
in patients with AF and HF with reduced systolic function is the
objective outcomes, such as mortality and hospitalization. While
a recent large RCT failed to demonstrate significant mortality
benefit in unselected populations, two recent randomized
trials have demonstrated that catheter ablation of AF in HF
patients with reduced systolic function population results in
significant improvement in all-cause mortality as well as fewer
HF hospitalizations.
52,58,59
The first of these studies was the
AATAC study, which randomized 203 patients with New York
Heart Association functional class II to III HF and an LVEF
<40% to catheter ablation (n=102) or amiodarone rhythm
control (n=101).
52
After 24–27 months of follow-up patients
in the ablation group had a significantly greater freedom from
recurrent AF (70% vs. 34%; P<0.001). In addition, the secondary
endpoints of unplanned hospitalization and all-cause mortality
were both significantly reduced (45% and 56% respectively),
corresponding to a NNT of 3.8 for unplanned hospitalization
and 10 for all-cause mortality. The second study, CASTLE-AF,
randomized patients with symptomatic paroxysmal or persistent
AF, New York Heart Association class II-IV HF, and an LVEF
≤35% to catheter ablation (179 patients) or medical therapy
(184 patients).
58
All patients had a cardiac implantable device
(ICD or CRT-ICD). After a median follow-up of 37.8 months,
patients in the ablation group were significantly less likely to meet
the primary composite end point of all-cause mortality or HF
Canadian Journal of General Internal Medicine
6 Volume 13, Special Issue 1, 2018
What is the Latest on Catheter Ablation of Atrial Fibrillation?
admission (16.1% absolute reduction; HR 0.62; 95% CI 0.43–0.87;
p=0.006). Similar to AATAC, there was a 47% relative reduction
in all-cause mortality (HR 0.53; 95% CI 0.32–0.86) and a 44%
reduction in HF hospitalization (HR 0.56; 95% CI 0.37–0.83).
The third study was CAMERA-MRI, which evaluated catheter
ablation vs. medical rate control in 68 patients with persistent
AF and left ventricular systolic dysfunction (LVEF ≤45%).
57
AF burden was assessed in ablation patients via implanted loop
recorder, and serial holter monitors in the medical rate control
patients. The primary endpoint was change in the LVEF on
magnetic resonance imaging (MRI) at six months. The authors
observed an 18±13% absolute improvement in the ablation arm
vs. 4.4±13% in the rate control arm (P<0.0001). The absence of
ventricular scar, as defined by late gadolinium enhan cement on
cardiac MRI, predicted greater improvement in LVEF (22.3% vs.
11.6% in those with scar, p=0.0069), and a greater likelihood of
LVEF normalization (73% vs. 21% in those with scar, P=0.009).
As such, it is possible that MRI may be used to prospectively
identify HF patients with reduced systolic function who may
benefit from catheter ablation of AF.
Taken together these studies demonstrate that catheter
ablation is associated with an improvement in ejection fraction
and clinical outcomes when compared to medical therapy. Most
striking is the observation that these adverse outcomes seem to
be more linked to the overall AF burden. Specifically, the clinical
benefit observed in CASTLE-AF was not dependent on the
complete elimination of AF. Notably, while 63.1% of patients in
the ablation group and 21.7% of patients in the medical therapy
group were free of recurrence at the 60-month follow-up visit,
the time in AF was reduced to ~25% in the ablation group
compared to ~60% in the medical therapy group. A subsequent
analysis of these patients demonstrated an AF burden <5% was
associated with a more than 3 times significantly greater freedom
from all-cause mortality or HF hospitalization at 1 year, when
compared to greater burdens of AF. It is hypothesized that the
reduction in AF burden facilitates improvement in cardiac
hemodynamic function (including cardiac output), autonomic
nervous system performance, and reverse remodeling, which
could also explain the lack of benefit observed in the rate control
group in CAMERA-MRI.
Lifestyle Intervention to Target AF Perpetuating
Substrate
AF is a complex chronic cardiovascular condition, with modifiable
lifestyle and cardiovascular risk factors impacting the risk for
AF development, AF progression, and AF recurrence after
cardioversion and catheter ablation. Modifiable risk factors
such as hypertension, obstructive sleep apnea, obesity, physical
Figure 2. Risk factor management targets and strategies from the ARREST-AF
cohort study. (ACEI - angiotensin converting enzyme inhibitor; AHI – apnea-
hypopnea index; ARB – angiotensin receptor blocker; BP - blood pressure;
CPAP - continuous positive airway pressure; LDL – low density lipoprotein;
TG – triglycerides). Reproduced with permission from Lau et al.
60
inactivity, alcohol and tobacco use, and diabetes mellitus have
all been shown to significantly contribute to AF frequency,
duration, and symptom severity. As such, interventions to
optimally manage these comorbidities have been postulated to
improve outcomes.
The ARREST-AF cohort study examined 149 patients with a
body mass index ≥27 kg/m2 and ≥1 cardiac risk factors, dividing
them into 61 patients who opted for risk factor management
(RFM) and 88 control subjects (Figure 2). In the RFM group:
blood pressure was treated to a target of <130/80 mmHg (ACEI/
ARB preferred), weight management targeted a >10% weight loss
to a BMI <27 kg/m2, exercise was targeted to start at 90 minutes
per week increasing to 250 minutes per week, obstructive sleep
apnea (AHI ≥30) was treated with CPAP therapy, lipids were
treated to contemporary targets, with elevated fasting blood sugar/
HbA1c treated with metformin to target an HbA1c <7%. At a
mean follow-up of ~42 months post ablation the RFM groups
achieved greater reductions in weight (−13.2±5.4 kg vs. −1.5±5.1
kg; p=0.002), blood pressure (34.1±7.5 mmHg vs. 20.6±3.2 mmHg;
p=0.003), glycemic control (HbA1c levels <7% in 100% vs. 29%;
p=0.001), and lipid values (controlled in 46.2% vs. 17%; p=0.01).
Arrhythmia-free survival rates after catheter ablation were 87%
with RFM compared with 18% for the control group (p<0.001),
with a significantly greater reduction in symptom scores and
global well-being (p<0.001).
Canadian Journal of General Internal Medicine
Volume 13, Special Issue 1, 2018 7
Andrade et al.
Conclusion
Catheter ablation is an effective treatment for AF. Pulmonary
vein isolation remains the cornerstone of AF ablation procedures,
with considerable effort having been directed towards developing
technologies to achieve safer and more durable lesions. Ongoing
research is being invested in studying ablation strategies to
improve outcomes in various AF populations.
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