PDF Archive

Easily share your PDF documents with your contacts, on the Web and Social Networks.

Share a file Manage my documents Convert Recover PDF Search Help Contact

fitness and devpt of AF .pdf

Original filename: fitness and devpt of AF.pdf

This PDF 1.7 document has been generated by PDFium, and has been sent on pdf-archive.com on 05/11/2015 at 19:10, from IP address 99.229.x.x. The current document download page has been viewed 330 times.
File size: 310 KB (4 pages).
Privacy: public file

Download original PDF file

Document preview

Fitness and the Development of Atrial Fibrillation
Advay G. Bhatt, MD; Kevin M. Monahan, MD


he beneficial effect of exercise on most aspects of cardiovascular disease is well established with a salutary effect
on the incidence of coronary artery disease (CAD), congestive
heart failure, and premature death in those who participate in
regular physical activity.1,2 This effect becomes apparent with
moderate increases in activity without a defined upper limit
of toxicity. For cardiac arrhythmias, atrial fibrillation (AF)
in particular, the story appears more complex. In fact, only
limited studies have been published on the beneficial effect
of physical activity on AF, whereas a number of case-control
studies have emphasized the deleterious effect of exercise
when performed at sustained high levels.3,4

Article see p 1827
The pathophysiology of AF is highly heterogeneous and
complex. Among the contributing clinical factors that lead to
the development and progression of AF are advanced age, left
ventricular dysfunction, valvular disease, CAD, diabetes mellitus, and hypertension.1 These physiological stressors alter
the normal electrophysiological substrate of a small, rapidly
conducting, uniformly repolarizing medium through fibrosis,
inflammation, oxidation, and altered ion channel physiology
to one adversely remodeled to support re-entry and repetitive
pulmonary vein and atrial firing.5,6
The extent of structural and electric remodeling of the
atria generally becomes apparent only once AF is clinically
established. By that point, risk factor (RF) modification may
reduce the frequency and duration of AF paroxysms and theoretically may slow the progression to a more persistent pattern,
but maintenance of sinus rhythm requires an ablative or pharmacological approach to make the atrial milieu less favorable
for AF. Promising developments in imaging and therapeutic
energy delivery to target the atrial substrate supporting AF7
have recently advanced the former, whereas antiarrhythmic
drug development has been highly disappointing for longer
than the last 2 decades. Despite these advances in mechanismdirected approaches for AF ablation, the long-term durability
remains suboptimal, given progressive adverse remodeling.7,8
The realization that structural and electric remodeling was
responsible for the majority of AF fueled the investigation
of agents that could attenuate or prevent atrial inflammation
and fibrosis such as statins, angiotensin blockade, aldosterone
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From Boston University School of Medicine, Boston, MA.
Correspondence to Kevin M. Monahan, MD, Boston University School
of Medicine, Arrhythmia Center, 88 E Newton St, C8, Boston, MA 02118.
E-mail kevin.monahan@bmc.org
(Circulation. 2015;131:1821-1823.
DOI: 10.1161/CIRCULATIONAHA.115.016596.)
© 2015 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.115.016596

blockade, and antioxidants, collectively labeled upstream
therapies.9–11 Although each drew support from animal models of AF models and substudy analyses of large human trials, enthusiasm waned with the results of prospective studies
focused on AF as an end point.
At the same time, there has been an emerging body of
evidence that several cardiometabolic RFs for AF, including
obstructive sleep apnea (OSA), obesity, and sedentary lifestyle, are associated with adverse atrial electric and structural
remodeling that supports AF:
1. The role of OSA role in the development of AF is likely
related to atrial stretch, autonomic imbalance, oxidative
stress, and inflammation. Dimitri et al12 demonstrated
that OSA is associated with volumetric and electric atrial
remodeling. OSA has been clinically associated with a
25% greater risk of recurrent AF after catheter ablation.13
Furthermore, continuous positive airway pressure for
OSA is associated with significantly improved AF-free
survival after ablation comparable to that of individuals
without OSA; ablation in untreated OSA has success
rates comparable to those of medical therapy alone.14
2. Obesity is similarly associated with atrial stretch, autonomic imbalance, oxidative stress, and inflammation,
as well as increased pericardial fat, an emerging marker
of cardiovascular risk. The difficulty in evaluating the
role of obesity in AF is confounded by the coexistence
of other cardiometabolic RFs and OSA. Abed et al15
demonstrated that in sheep excessive caloric intake leading to weight gain was associated with adverse atrial
remodeling marked by increased left atrial mass, fibrosis, inflammation, slower and more heterogeneous atrial
conduction, and greater burden of AF. When the sheep
were subjected to caloric restriction leading to weight
reduction, this resulted in favorable structural and electric atrial changes, that is, reverse remodeling.16 Similar
beneficial changes have recently been reported with
weight reduction in humans.17
3. It is well documented that regular and moderate physical activity improves various parameters of cardiometabolic health and prevents the development of RFs or
cardiovascular disease through its beneficial effects on
endothelial function, inflammation, and oxidative stress.
Several observational studies found that increased physical activity was associated with a reduction in AF.1–3 On
the other hand, high-level competitive endurance training in marathon runners, cyclists, and elite cross-country
skiers has been associated with an increased risk of AF.3,4
The mechanisms for this association are related to repetitive and extreme hemodynamic loads, heightened vagal
tone, fibrosis, and left atrial enlargement.3,4
The Aggressive Risk Factor Reduction Study for Atrial
Fibrillation and Implications for the Outcome of Ablation

Downloaded from http://circ.ahajournals.org/
at University of Toronto on November 5, 2015

1822  Circulation  May 26, 2015
(ARREST-AF) cohort study extended the paradigm of aggressive
RF modification to those undergoing catheter ablation of AF.18
Intensive RF modification focused on blood pressure and glycemic control, weight management, and OFA was associated with
marked improvement in parameters of cardiometabolic health,
improvements in cardiac structure, and reductions in burden of
AF. RF modification was associated with an ≈5-fold increase in
AF-free survival. However, the way in which increased physical
activity or cardiorespiratory fitness, in conjunction with RF modification, modulates treatment of AF has not been determined.
In this issue of Circulation, Qureshi et al19 examine the
relationship of cardiorespiratory fitness and the development
of incident AF after adjusting for cardiometabolic RFs and
medications. The investigators report the results of a retrospective cohort analysis of the Henry Ford Exercise Testing
(FIT) project enrolling 69 885 subjects between 1991 and 2009
referred for clinically indicated exercise testing. Individuals
with pre-existing AF, atrial flutter, or left ventricular dysfunction were excluded. The final study cohort included 64 561
individuals in whom cardiorespiratory fitness, as measured
by metabolic equivalents of task (METs), was assessed for
development of AF via linkage to International Classification
of Disease, Ninth Revision codes in insurance claim files over
a mean follow-up of 5.4 years. Cardiorespiratory fitness was
stratified into 4 categories of <6, 6 to 9, 10 to 11, and >11
METs. As would be anticipated, there were significant trends
toward accumulating cardiometabolic RFs and advancing age
as cardiorespiratory fitness declines. A nested Cox proportional
hazard model was used to sequentially control for 3 groupings
of RFs and medications. The investigators found that the unadjusted 5-year cumulative incidences of AF across the 4 strata of
cardiorespiratory fitness were 18.8%, 9.5%, 5.0%, and 3.7%,
respectively. For every 1-MET increase, there was an associated 7% decrease in the risk of AF. There was no attenuation of
benefit when cardiorespiratory fitness was >10 METs.
The limitations of this study include the retrospective
design reliant on coding of clinical characteristics at the time
of exercise testing and linkage to billing codes to the subsequent development of AF. An ECG diagnosis of AF would
have been more powerful, and the inclusion of atrial flutter as
an end point would have been justified given the close pathophysiological underpinnings and clinical relationship.20
A remaining concern is the generalizability of the study.
The population is largely a middle-aged cohort referred for
stress testing, which presumably has higher prevalence of cardiovascular disease and RFs for AF. Furthermore, the effect
of cardiorespiratory fitness on reduction in AF was more pronounced in obese and older individuals, presumed to have
higher risk of AF. This limits extrapolation to intermediate- or
low- risk groups. It would be reasonable to assume that less fit
patients were more likely to be limited by or diagnosed with
CAD or heart failure after stress testing. The investigators
addressed this concern with adjustment for incident CAD as
a time-varying covariate and subgroup analyses of those with
incident left ventricular dysfunction or pre-existing CAD; the
relationship of cardiorespiratory fitness to AF remained significant. However, incident cardiometabolic RF development
over time before the coding of AF was not ascertained and
may confound the result.

The fact that blacks are well represented strengthens the
conclusion that cardiorespiratory fitness is inversely related to
AF for 2 reasons. First, most AF studies enroll a lower proportion of ethnic minorities.1 Second, blacks are known to have a
high burden of cardiometabolic RFs but a lower incidence of
AF.1 Despite the potential for dilution of the observed effect,
the results remain significant.
Overall, this study represents the first cohort to establish
a link between cardiorespiratory fitness and incidence of AF,
supporting the aforementioned link between physical activity
and AF. However, we should recognize that physical activity
and cardiometabolic RFs are different physiological markers
and that each has a different association with risk of cardiovascular disease.21 It would not be surprising if there were a
nonlinear relationship between cardiorespiratory fitness and
AF, given this difference and the evident adverse effects in
competitive endurance athletes. We should be careful not to
overinterpret the results and to intensify the exercise prescription for our patients until several issues are further elucidated:
(1) the potential for an upper limit of benefit, given concerns
that high-level and sustained exercise training may adversely
affect remodeling; (2) the potential benefit of exercise training
once AF is established; and (3) the optimal way to improve
cardiorespiratory fitness in at-risk populations.
The study is promising in that it suggests further reason
to encourage exercise and opens the door to a strategy that
complements ARREST-AF and ablation to mitigate the burgeoning epidemic of AF in the future.


1. Magnani JW, Rienstra M, Lin H, Sinner MF, Lubitz SA, McManus DD,
Dupuis J, Ellinor PT, Benjamin EJ. Atrial fibrillation: current knowledge and future directions in epidemiology and genomics. Circulation.
2011;124:1982–1993. doi: 10.1161/CIRCULATIONAHA.111.039677.
2. Rienstra M, McManus DD, Benjamin EJ. Novel risk factors for atrial fibrillation: useful for risk prediction and clinical decision making? Circulation.
2012;125:e941–e946. doi: 10.1161/CIRCULATIONAHA.112.112920.
3. Predel HG. Marathon run: cardiovascular adaptation and cardiovascular
risk. Eur Heart J. 2014;35:3091–3098. doi: 10.1093/eurheartj/eht502.
4. O’Keefe JH, Patil HR, Lavie CJ, Magalski A, Vogel RA, McCullough PA.
Potential adverse cardiovascular effects from excessive endurance exercise.
Mayo Clin Proc. 2012;87:587–595. doi: 10.1016/j.mayocp.2012.04.005.
5. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance
in atrial fibrillation. J Am Coll Cardiol. 2008;51:802–809. doi: 10.1016/j.
6. Nattel S, Burstein B, Dobrev D. Atrial remodeling and atrial fibrillation:
mechanisms and implications. Circ Arrhythm Electrophysiol. 2008;1:62–
73. doi: 10.1161/CIRCEP.107.754564.
7. Nishida K, Datino T, Macle L, Nattel S. Atrial fibrillation ablation:
translating basic mechanistic insights to the patient. J Am Coll Cardiol.
2014;64:823–831. doi: 10.1016/j.jacc.2014.06.1172.
8. Teh AW, Kistler PM, Lee G, Medi C, Heck PM, Spence SJ, Morton JB,
Sanders P, Kalman JM. Long-term effects of catheter ablation for lone
atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation. Heart Rhythm. 2012;9:473–480. doi:
9. Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S,
Connolly SJ. Prevention of atrial fibrillation with angiotensin-converting
enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J
Am Coll Cardiol. 2005;45:1832–1839. doi: 10.1016/j.jacc.2004.11.070.
10. Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Shi
H, Vincent J, Pitt B; EMPHASIS-HF Study Investigators. Eplerenone

Downloaded from http://circ.ahajournals.org/ at University of Toronto on November 5, 2015

Bhatt and Monahan   Fitness and the Development of Atrial Fibrillation   1823
and atrial fibrillation in mild systolic heart failure: results from the
EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And
SurvIval Study in Heart Failure) study. J Am Coll Cardiol. 2012;59:1598–
1603. doi: 10.1016/j.jacc.2011.11.063.
11. Rahimi K, Emberson J, McGale P, Majoni W, Merhi A, Asselbergs FW,
Krane V, Macfarlane PW; PROSPER Executive. Effect of statins on atrial
fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials. BMJ. 2011;342:d1250.
12. Dimitri H, Ng M, Brooks AG, Kuklik P, Stiles MK, Lau DH, Antic N,
Thornton A, Saint DA, McEvoy D, Antic R, Kalman JM, Sanders P. Atrial
remodeling in obstructive sleep apnea: implications for atrial fibrillation.
Heart Rhythm. 2012;9:321–327. doi: 10.1016/j.hrthm.2011.10.017.
13. Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis
of obstructive sleep apnea as predictor of atrial fibrillation recurrence
after catheter ablation. Am J Cardiol. 2011;108:47–51. doi: 10.1016/j.
14. Fein AS, Shvilkin A, Shah D, Haffajee CI, Das S, Kumar K, Kramer DB,
Zimetbaum PJ, Buxton AE, Josephson ME, Anter E. Treatment of obstructive
sleep apnea reduces the risk of atrial fibrillation recurrence after catheter ablation. J Am Coll Cardiol. 2013;62:300–305. doi: 10.1016/j.jacc.2013.03.052.
15. Abed HS, Samuel CS, Lau DH, Kelly DJ, Royce SG, Alasady M, Mahajan
R, Kuklik P, Zhang Y, Brooks AG, Nelson AJ, Worthley SG, Abhayaratna
WP, Kalman JM, Wittert GA, Sanders P. Obesity results in progressive
atrial structural and electrical remodeling: implications for atrial fibrillation. Heart Rhythm. 2013;10:90–100. doi: 10.1016/j.hrthm.2012.08.043.
16. Mahajan R, Brooks A, Manavis J, Wood J, Finnie J, Sameul C, Lau D,
Selvanayagam J, Roberts-Thomson K, Sanders P. Atrial fibrillation and

obesity: impact of weight reduction on the atrial substrate. Heart Lung
Circ. 2013;22:S1–S2.
17. Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B, Middeldorp
ME, Lorimer MF, Lau DH, Antic NA, Brooks AG, Abhayaratna WP,
Kalman JM, Sanders P. Effect of weight reduction and cardiometabolic
risk factor management on symptom burden and severity in patients with
atrial fibrillation: a randomized clinical trial. JAMA. 2013;310:2050–2060.
doi: 10.1001/jama.2013.280521.
18. Pathak RK, Middeldorp ME, Lau DH, Mehta AB, Mahajan R, Twomey D,
Alasady M, Hanley L, Antic NA, McEvoy RD, Kalman JM, Abhayaratna
WP, Sanders P. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF
cohort study. J Am Coll Cardiol. 2014;64:2222–2231. doi: 10.1016/j.
19. Qureshi WT, Alirhayim Z, Blaha MJ, Juraschek SP, Keteyian SJ, Brawner
CA, Al-Mallah MH. Cardiorespiratory fitness and risk of incident atrial
fibrillation: results from the Henry Ford Exercise Testing (FIT) Project.
Circulation. 2015;131:1827–1834.
20. Anné W, Willems R, Van der Merwe N, Van de Werf F, Ector H, Heidbüchel
H. Atrial fibrillation after radiofrequency ablation of atrial flutter: preventive effect of angiotensin converting enzyme inhibitors, angiotensin II
receptor blockers, and diuretics. Heart. 2004;90:1025–1030. doi: 10.1136/
21. Williams PT. Physical fitness and activity as separate heart disease risk
factors: a meta-analysis. Med Sci Sports Exerc. 2001;33:754–761.
Key Words: Editorials ◼ atrial fibrillation ◼ exercise tolerance

Downloaded from http://circ.ahajournals.org/ at University of Toronto on November 5, 2015

Fitness and the Development of Atrial Fibrillation
Advay G. Bhatt and Kevin M. Monahan
Circulation. 2015;131:1821-1823; originally published online April 22, 2015;
doi: 10.1161/CIRCULATIONAHA.115.016596
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2015 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539

The online version of this article, along with updated information and services, is located on the
World Wide Web at:

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located,
click Request Permissions in the middle column of the Web page under Services. Further information about
this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
Subscriptions: Information about subscribing to Circulation is online at:

Downloaded from http://circ.ahajournals.org/ at University of Toronto on November 5, 2015

fitness and devpt of AF.pdf - page 1/4
fitness and devpt of AF.pdf - page 2/4
fitness and devpt of AF.pdf - page 3/4
fitness and devpt of AF.pdf - page 4/4

Related documents

fitness and devpt of af
wearable technolog robert janikowski 2017
xarelto   compare rx prices
information leaflet and consent form vo2 max jan 2016
common medical abbreviation
1 surgical management of congenital heart disease

Related keywords