[ Editorials Point and Counterpoint ]
POINT:
Should All Patients With
Atrial Fibrillation Who Are
About to Undergo Pulmonary
Vein Ablation Be Evaluated
for OSA? Yes
Reena Mehra, MD, FCCP
Oussama Wazni, MD
Cleveland, OH
ABBREVIATIONS: AF = atrial fibrillation; CSA = central sleep
apnea; CV = cardiovascular; PAP = positive airway pressure;
PVI = pulmonary vein isolation; RCT = randomized
controlled trial
Data over the past several decades have amassed
supporting the role of OSA as an instigator of atrial
fibrillation (AF) and specifically as an important factor
to consider in the management of AF. AF is projected
to increase 5 fold, afflicting up to 16 million individuals
by the year 2050, with > $6.7 billion in costs
annually.1-3 OSA is also highly prevalent (15%-30%) in
the general population,4 with estimates even higher in
those with cardiac arrhythmia such as AF, the latter
with a prevalence upwards of 50%.5 This high
AFFILIATIONS: From the Sleep Disorders Center (Dr Mehra),
Neurologic Institute, Cleveland Clinic; and the Cardiac Pacing and
Electrophysiology, Heart and Vascular Institute (Dr Wazni), Cleveland
Clinic.
FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have
reported to CHEST the following: R. M. has received National
Institutes of Health (NIH) funding for which she has served as
principal investigator for National Heart, Lung, and Blood Institute
[Grants R01HL109493 and R21HL108226]. Her institution has
received positive airway pressure machines and equipment from
Philips Respironics and Resmed for use in NIH-funded research. She
has received honorarium from the American Academy of Sleep
Medicine for speaking, serves as an Associate Editor for the CHEST,
and has received royalties from Up to Date. None declared (O. W.).
CORRESPONDENCE TO: Reena Mehra, MD, FCCP, Sleep Disorders
Center, Neurologic Institute, Respiratory Institute, Heart and Vascular
Institute and Lerner Research Institute, 9500 Euclid Ave, Cleveland
Clinic, Cleveland, OH 44195; e-mail: mehrar@ccf.org
Copyright Ó 2018 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: https://doi.org/10.1016/j.chest.2018.06.042
1008 Point and Counterpoint
population-specific attributable risk of OSA, therefore,
has the potential to amplify cardiac arrhythmogenic
potential and attendant negative health consequences
as well as responsiveness to AF interventions to quite a
substantial degree. Overall, existing OSA-AF data
comprise experimental data that have elucidated
specific mechanistic underpinnings, epidemiologic
studies that have characterized high-magnitude cross-
sectional and longitudinal associations, and clinic-
based data, much of which have focused upon AF
outcomes postintervention with cardioversion or
ablation.6
A number of underlying pathophysiologic mechanisms
have been implicated in OSA-related cardiac
arrhythmogenic risk, including autonomic nervous
system fluctuations, intermittent hypoxia, alterations in
carbon dioxide levels, swings in intrathoracic pressures,
and up-regulation of pathways of systemic
inflammation. Overall, we can consider OSA as a series
of repeated precipitating acute physiologic insults (ie,
repetitive hemodynamic, hypoxemic, and autonomic
surges), resulting in cardiac structural and electrical
remodeling that operate to create an altered
arrhythmogenic substrate in apnea-induced
arrhythmia. Although there are most assuredly
synergies of these pathways, perhaps data are strongest
in identifying OSA-related sympathovagal imbalances
as the primary culprit. Intrinsic to the physiology of
obstructive respiratory events (ie, apneas and
hypopneas) are increasing respiratory efforts of
progressive magnitude to achieve restoration of airway
patency. Strong sympathetic nervous system responses
are elicited subsequent to the upper airway obstruction,
likely exerted by interactive effects of central
respiratory sympathetic coupling, hypoxia,
hypercapnia, and absence of sympathoinhibition from
normal lung initiation reflexes.7 In direct opposition to
these sympathetic surges are enhanced vagal efferent
outflow to the heart and bradycardia observed during
the apneic event (ie, the diving reflex). These vagal
influences shorten the atrial effective refractory period
(ie, enhance vulnerability to excitatory stimuli).
Support for the role of autonomic influences in OSAa
comes from a canine model in which ablation of the
right ganglionated plexus resulted in inhibition of
apnea-induced AF.8 Existing data therefore provide a
[ 154#5 CHEST NOVEMBER 2018 ]
strong pathophysiologic rationale for OSA-induced
alterations of the cardiac substrate increasing atrial
arrhythmogenic propensity.
Given that antiarrhythmic medications are often
ineffective and have serious potential side effects,
pulmonary vein isolation (PVI) has become an
effective means of AF treatment and cure for specific
patients, particularly as randomized clinical trial data
have shown that PVI is associated with lower AF
recurrence compared with those patients randomized
to antiarrhythmic medications.9 Although PVI,
focused on abolishing triggers from and adjacent to
the pulmonary veins, is a mainstay approach to
address AF, recurrence of AF remains quite high
despite development of novel PVI-based technologies.
Specifically, the percentage of success of PVI at 1 to 2
years disappointingly remains at 40% to 50% for
persistent AF and 50% to 75% for paroxysmal AF.10,11
Predictors of postablation AF include hypertension
(pooled risk ratio [RR], 2.70; 95% confidence interval
[CI], 1.43-5.07), age (RR, 1.03; 95% CI, 1.00-1.06), left
atrial diameter (RR, 1.11; 95% CI, 1.05-1.18), and
permanent AF (RR, 2.23; 95% CI, 1.08-4.59).12
Importantly, not only does OSA share AF risk factors
of increasing age and obesity, it is also a predictor of
these very risks of AF ablation failure; for example,
OSA has been identified as a strong predictor of
incident hypertension.13 Data from several
randomized controlled trials show improvement in BP
with OSA treatment in response to continuous
positive airway pressure therapy, thereby providing a
strong rationale for identification and treatment of
OSA before AF ablation to optimize sustained
response.14
In terms of the benefit of reversal of OSA
pathophysiology on AF recurrence, several
investigations have consistently demonstrated a
reduction in AF recurrence subsequent to
cardioversion or ablation with CPAP treatment
compared with lack of treatment.15-18 Furthermore,
there are data to support that untreated OSA in those
undergoing ablation with nonpulmonary vein triggers
had an 8 fold higher likelihood of procedure failure.18
Recent data support that although the pulmonary veins
are the major triggers for AF in OSA, extrapulmonary
vein triggers are also commonly present, and ablation
of these triggers may improve clinical outcomes
chestjournal.org
compared with PVI alone.19 For example, in a clinic-
based study, among those with both OSA and AF who
underwent direct current cardioversion, those who
used CPAP therapy had a lower 12-month recurrence
of AF compared with those without AF (42% vs 82%,
P ¼ .013), with further analyses demonstrating that
those with a greater degree of untreated nocturnal
hypoxia were most susceptible to this increased
AF recurrence.16 Furthermore, a meta-analysis
focused on examination of the impact of CPAP
treatment in OSA in those undergoing catheter
ablation showed a 42% decreased risk of AF (RR, 0.58;
95% CI, 0.47-0.70) in those treated with CPAP with
greatest benefit in those were younger, obese,
and male20 and had consistent findings in other
aggregate data.21
The rationale for universal OSA assessment of those
who are undergoing PVI for AF is clearly supported
by the following: (1) the strong biologic plausibility
shown by experimental data confirming the role
of OSA-induced intermittent autonomic nervous
system fluctuations and impact of intrathoracic
pressure alterations on the thin-walled atria; (2) ability
to reverse recognized risk factors for AF recurrence,
such as hypertension, which has a strong evidence
base for improvement with OSA treatment; and (3)
consistent findings from many studies with pooled
estimates showing a 42% reduction of AF recurrence
in those with OSA who are treated with CPAP
vs those who are not treated after PVI.19,20 The
following domains identified by existing literature
support Hill’s tenants of causality of OSA and AF
(ie, strong magnitude of association, biologic
plausibility, and longitudinal association supporting
temporality). This combined with the high prevalence
and burden of OSA in this patient population provides
a strong and compelling basis for the broad
standardized assessment of OSA in patients with AF
undergoing PVI.
References
1. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M,
Zimetbaum P. Assessing the direct costs of treating nonvalvular
atrial fibrillation in the United States. Value Health. 2006;9(5):
348-356.
2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial
fibrillation in adults: national implications for rhythm management
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in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):
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1009
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9. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency
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1010 Point and Counterpoint
COUNTERPOINT:
Should All Patients With
Atrial Fibrillation Who Are
About to Undergo Pulmonary
Vein Ablation Be Evaluated
for OSA? No
Meghna P. Mansukhani, MD
Virend K. Somers, MD, PhD, FCCP
Sean M. Caples, DO, MS
Rochester, MN
In many respects, atrial fibrillation (AF) carries serious
implications, with an increased associated risk of
stroke, heart failure, and even death.1-3 For the patient
who, despite attempts at restoration of rhythm by
electrical or chemical means, has an arrhythmia that
persists to the point of consideration for pulmonary
vein ablation, the stakes are often raised. It is no
wonder, then, that given the association between AF
and OSA, some may advocate for universal screening
for OSA of such patients in the hopes of a successful
rhythm outcome.
True, there is an undeniable link between OSA and AF.
Dr Mehra and colleagues4-6 have helped lead the way in
drawing attention to this relationship and should be
commended. Multiple pathophysiologic mechanisms
have been proposed for the development of AF in
AFFILIATIONS: From the Center for Sleep Medicine (Drs Mansukhani
and Caples); Department of Cardiovascular Diseases (Dr Somers),
Mayo Clinic; and the Division of Pulmonary and Critical Care
Medicine (Dr Caples), Mayo Clinic.
FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have
reported to CHEST the following: M. P. M. is the principal investigator
on a research grant funded by ResMed Foundation evaluating the
effects of adaptive servoventilation treatment of central apnea
syndromes on health care utilization that is not relevant to the current
work. She is the recipient of a benefactor-sponsored career develop-
ment award at Mayo Clinic. Dr Somers is supported by research grants
from the National Institutes of Health (HL65176) and Philips
Respironics Foundation (gift to Mayo Foundation); is a consultant for
Respicardia, ResMed, U-Health, GlaxoSmithKline, Itamar, and Bayer;
is an investigator on the SERVE-HF Steering Committee; and is
working with Mayo Health Solutions and their industry partners on
intellectual property related to sleep and cardiovascular disease. None
declared (S. M. C.).
CORRESPONDENCE TO: Meghna P. Mansukhani, MD, Center for Sleep
Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail:
mansukhani.meghna@mayo.edu
Copyright Ó 2018 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: https://doi.org/10.1016/j.chest.2018.06.041
[ 154#5 CHEST NOVEMBER 2018 ]