JACC: CLINICAL ELECTROPHYSIOLOGY
3, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER INC.
EDITORIAL COMMENT
Triggers, Substrate, and Hypertension
in Atrial Fibrillation
How Does It All Add Up?*
Ratika Parkash, MS, MD
A trial fibrillation (AF) is the most common sus-
tained arrhythmia and is associated with sig-
nificant morbidity, mortality, and cost (1,2).
AF results from the occurrence of 3 mechanisms
(3,4): 1) single-circuit re-entry; 2) multiple circuit re-
entry; or 3) rapid focal ectopic activity. Maintenance
of AF requires that an appropriate substrate exist on
which a trigger can initiate re-entry. The substrate
for AF consists of 2 components: 1) altered electro-
physiological properties; and 2) altered structural
properties of the atrium. Uncontrolled hypertension
can result in several changes to the left atrial sub-
strate including effects on ion channel function and
increased atrial fibrosis (Figure 1) (5–7).
Despite advancements in ablation technologies over
the past decade, including contact force technology
and the second-generation cryoballoon, the recur-
rence rate of AF after catheter ablation remains high
(8–10). These observations have led those of us who
treat AF to examine other contributors to AF, with the
realization that ablation alone may be insufficient to
result in optimal arrhythmia control in patients. Hy-
pertension is an obvious target given that is the most
prevalent and potentially modifiable risk factor for AF
(11,12). Multiple animal and clinical human studies
have found a direct relationship between the risk of AF
and systolic and diastolic blood pressure (13–20).
SEE PAGE 164
In this issue of JACC: Clinical Electrophysiology,
Santoro et al. (21) report results of a carefully
*Editorials published in JACC: Clinical Electrophysiology reflect the views
of the authors and do not necessarily represent the views of JACC:
Clinical Electrophysiology or the American College of Cardiology.
From the QEII Health Sciences Center, Halifax, Nova Scotia, Canada. Dr.
Parkash has received honoraria and research grants from Bayer, Pfizer,
Boehringer Ingelheim, St. Jude Medical, and Medtronic.
VOL. 1, NO.
ISSN 2405-500X/$36.00
http://dx.doi.org/10.1016/j.jacep.2015.05.005
conducted prospective cohort study of 531 consecu-
tive patients who underwent ablation for AF grouped
by uncontrolled hypertension (n ¼ 160), controlled
hypertension (n ¼ 192), or no hypertension (n ¼ 179).
All patients underwent pulmonary vein (PV) antral
isolation with additional ablation performed for
non-PV triggers, as determined by operator discre-
tion. The main findings of this study were that un-
controlled hypertension, as measured before the
procedure, was associated with a significantly
increased risk of recurrence (40.6%) at a follow-up of
19  7.7 months after a single ablation procedure
compared with those patients who had controlled
hypertension (28.1%) or no hypertension (25.7%). The
presence of non-PV triggers was greater (58.8% vs.
33.3%) in the group with uncontrolled hypertension.
Ablation of non-PV triggers was associated with a
significant reduction in AF recurrence compared with
those whose non-PV triggers were left alone (69.8%
vs. 37.3%).
This study is certainly compelling in advancing the
notion that blood pressure control is indeed exqui-
sitely linked to recurrence of AF after catheter abla-
tion. There are, however, important caveats to this
study that prevent this trial from being definitive.
The lack of randomization is an obvious limitation of
the study, recognized by the authors. Most impor-
tantly, this study did not address the effect of
aggressive blood pressure control and its interaction
with outcomes of catheter ablation. This is a key
question that needs to be addressed in order to assess
how hypertension may affect the genesis of AF. Dif-
ferences in left atrial size and the presence of a left
atrial scar are also important confounders that
are known to have an effect on ablation outcome
(22,23). Important measurable and unmeasurable
confounders not accounted for in this study include
the duration of AF, presence of sleep apnea (23,24),
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 1, NO. 3, 2015
JUNE 2015:174–6
and variations in the autonomic nervous system,
which may introduce bias (25). The importance of
central sympathetic inhibition in hypertensive pa-
tients was demonstrated by Giannopoulos et al. (26),
where the use of moxonidine, a centrally acting
sympathoinhibitory agent, reduced the recurrence of
AF post-ablation at 12 months, without any major
effect on blood pressure. The reduction in AF
observed by Pokushalov et al. (27), in a study of renal
denervation as an adjunct to AF ablation, may have
been due to modulation of sympathetic outflow
rather than blood pressure reduction. Finally, the
ablation procedure itself differed among and within
groups; the determinants of when ablation for non-PV
triggers was performed are not reported.
Risk factor management for patients with AF
before catheter ablation is an emerging area of study
(24). A multicenter clinical trial (NCT00438113)
(SMAC AF [Atrial Substrate Modification
Aggressive Blood Pressure Lowering to Prevent AF])
is almost complete in Canada to demonstrate whether
substrate modification with aggressive blood pressure
lowering, with antihypertensive therapy, as an
adjunct to AF ablation has a beneficial effect for
reducing AF recurrence. Other studies examining
novel drug approaches to sympathetic modulation,
ganglionated plexus ablation, and other therapies
may also add to our increasing understanding of the
genesis of AF (28).
This study by Santoro et al. (21) confirms that AF
is not simply a rhythm disorder that can be tackled
by catheter ablation or through variation of that
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Parkash 175
Triggers, Substrate, and Hypertension in AF
F I G U R E 1 Mechanism of Blood Pressure Effect on Substrate for AF
Modified and reproduced with permission from Ehrlich et al. (7). BP ¼ blood pressure;
LV ¼ left ventricular.
With
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REPRINT REQUESTS AND CORRESPONDENCE: Dr.
Ratika Parkash, QEII Health Sciences Centre, HI Site,
1796 Summer Street, Room 2501D, Halifax, Nova
Scotia B3H 3A7, Canada. E-mail: Ratika.parkash@
nshealth.ca.
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