OSA and Cardiac Arrhythmogenesis: Mechanistic Insights.
A surge of data has reproducibly identified strong associations of OSA with cardiac arrhythmias. As an extension of epidemiologic and clinic-based findings, experimental investigations have made strides in advancing our understanding of the putative OSA and cardiac arrhythmogenesis mechanistic underpinnings. Although most studies have focused on the links between OSA and atrial fibrillation (AF), relationships with ventricular arrhythmias have also been characterized. Key findings implicate OSA-related autonomic nervous system fluctuations typified by enhanced parasympathetic activation during respiratory events and sympathetic surges subsequent to respiratory events, which contribute to augmented arrhythmic propensity. Other more immediate pathophysiologic influences of OSA-enhancing arrhythmogenesis include intermittent hypoxia, intrathoracic pressure swings leading to atrial stretch, and hypercapnia. Intermediate pathways by which OSA may trigger arrhythmia include increased systemic inflammation, oxidative stress, enhanced prothrombotic state, and vascular dysfunction. Long-term OSA-associated sequelae such as hypertension, atrial enlargement and fibrosis, ventricular hypertrophy, and coronary artery disease also predispose to cardiac arrhythmia. These factors can lead to a reduction in atrial effective refractory period, triggered and abnormal automaticity, and promote slowed and heterogeneous conduction; all of these mechanisms increase the persistence of reentrant arrhythmias and prolong the QT interval. Cardiac electrical and structural remodeling observed in OSA animal models can progress the arrhythmogenic substrate to further enhance arrhythmia generation. Future investigations clarifying the contribution of specific OSA-related mechanistic pathways to arrhythmia generation may allow targeted preventative therapies to mitigate OSA-induced arrhythmogenicity. Furthermore, interventional studies are needed to clarify the impact of OSA pathophysiology reversal on cardiac arrhythmogenesis and related adverse outcomes.
Division of Pulmonary, Critical Care, and Sleep Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH. Electronic address: anna.may@uhhospitals.org.
Anna M
AM
May
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
David R
DR
Van Wagoner
Neurologic Institute, Respiratory Institute, Heart and Vascular Institute and Molecular Cardiology Department, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
Reena
R
Mehra
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology
OSA; arrhythmia; automaticity; autonomic nervous system dysregulation; cardiac conduction; effective refractory period
Am J Epidemiol. 2013 May 1;177(9):1006-14
23589584
Value Health. 2006 Sep-Oct;9(5):348-56
16961553
PLoS One. 2013 Oct 04;8(10):e75838
24124516
J Appl Physiol (1985). 2008 Jan;104(1):218-23
18006871
Can Respir J. 2011 Nov-Dec;18(6):338-48
22187690
Oxid Med Cell Longev. 2015;2015:608438
26167241
J Hypertens. 2008 Jun;26(6):1163-8
18475154
Acta Cardiol. 2014 Apr;69(2):175-84
24783469
Heart Rhythm. 2011 Dec;8(12):1933-9
21767520
Pacing Clin Electrophysiol. 2005 Aug;28(8):819-25
16105010
Korean Circ J. 2015 May;45(3):184-91
26023305
Hypertension. 2012 Jul;60(1):172-8
22585944
J Hypertens. 2000 Sep;18(9):1257-62
10994757
Int J Cardiol. 2009 Aug 21;136(3):258-62
18657327
Clin Cardiol. 2010 Jun;33(6):E35-9
20552591
Sleep Breath. 2012 Mar;16(1):83-8
21221821
Clin Sci (Lond). 2003 Dec;105(6):671-6
12857349
Heart. 2009 Nov;95(22):1872-8
19643769
Sleep Med. 2007 Jan;8(1):51-9
17023210
Ann Noninvasive Electrocardiol. 2014 May;19(3):226-33
24192528
J Electrocardiol. 2011 Jul-Aug;44(4):478-82
21704224
Am J Respir Crit Care Med. 2006 Apr 15;173(8):910-6
16424443
J Electrocardiol. 2008 Nov-Dec;41(6):567-74
18790499
J Appl Physiol (1985). 2000 Jan;88(1):257-64
10642388
Sleep. 2007 Jun;30(6):755-66
17580597
Am J Med. 1987 Mar 20;82(3A):18-23
3565423
Acta Physiol Scand. 2003 Mar;177(3):385-90
12609010
J Appl Physiol (1985). 1997 Apr;82(4):1071-8
9104841
Am J Cardiol. 2014 Oct 1;114(7):1049-52
25118122
Circulation. 1997 Sep 2;96(5):1686-95
9315565
Circ Arrhythm Electrophysiol. 2013 Apr;6(2):287-93
23515262
J Cardiovasc Pharmacol. 2015 Dec;66(6):523-9
26335221
Sleep Med. 2012 May;13(5):510-6
22437139
Respir Physiol Neurobiol. 2004 Jul 20;141(2):145-55
15239965
Circulation. 1998 Sep 8;98(10):946-52
9737513
Sleep Med. 2007 Aug;8(5):478-83
17512787
Lancet. 2009 Jan 10;373(9658):155-66
19135613
Curr Hypertens Rep. 2008 Jun;10(3):222-6
18765094
Exp Physiol. 2015 Feb 01;100(2):130-5
25398715
Prog Cardiovasc Dis. 2009 Jan-Feb;51(4):324-38
19110134
J Am Coll Cardiol. 2005 Jun 21;45(12):2008-11
15963401
Circulation. 2001 Dec 11;104(24):2886-91
11739301
Adv Ther. 2009 Sep;26(9):847-57
19768638
Auton Neurosci. 2013 Oct;177(2):148-53
23622813
Eur Respir J. 2005 Apr;25(4):677-81
15802342
N Engl J Med. 2005 Mar 24;352(12):1206-14
15788497
Am J Respir Crit Care Med. 2010 Sep 15;182(6):826-33
20508215
Europace. 2010 Aug;12(8):1084-9
20488856
Chest. 2007 May;131(5):1379-86
17494787
Mayo Clin Proc. 2004 Aug;79(8):1036-46
15301332
Cardiovasc Res. 2010 Nov 1;88(2):241-9
20621924
Cardiology. 2011;118(1):68-73
21454976
J Appl Physiol (1985). 2007 May;102(5):1806-14
17272404
J Hypertens. 2010 May;28(5):1074-82
20411620
Eur Heart J. 2012 Sep;33(17):2206-12
22453648
Am J Respir Crit Care Med. 2002 Aug 1;166(3):279-86
12153958
Rev Esp Cardiol. 2011 Jul;64(7):551-3
21616576
J Am Coll Cardiol. 2007 Feb 6;49(5):565-71
17276180
J Cardiovasc Electrophysiol. 2016 Aug;27(8):1001-10
27060686
Am J Cardiol. 2008 Dec 1;102(11):1557-61
19026314
World J Cardiol. 2013 Jun 26;5(6):157-63
23802045
J Pathol. 1997 Mar;181(3):338-46
9155722
Ann Intern Med. 2013 Dec 3;159(11):721-8
24297188
Circulation. 2003 May 27;107(20):2589-94
12743002
Sleep. 2016 Jul 01;39(7):1361-9
27091532
Heart Fail Rev. 2009 Sep;14(3):143-53
18807180
Hellenic J Cardiol. 2006 Jan-Feb;47(1):13-20
16532711
J Appl Physiol (1985). 2005 Nov;99(5):2028-35
16002771
Heart Rhythm. 2013 Mar;10(3):331-7
23178687
J Am Coll Cardiol. 2006 Jan 17;47(2):362-7
16412861
J Physiol. 1958 Nov 10;144(1):148-66
13599115
J Interv Card Electrophysiol. 2013 Apr;36(3):247-53
23179919
J Sleep Res. 2009 Sep;18(3):329-36
19549077
Coron Artery Dis. 1996 Jun;7(6):475-8
8889364
Pacing Clin Electrophysiol. 2003 Jul;26(7 Pt 1):1446-53
12914620
Int J Cardiol. 2010 Oct 8;144(2):257-9
19211166
Am J Cardiol. 2011 Jul 1;108(1):47-51
21529734
Eur J Appl Physiol. 2013 Feb;113(2):489-96
22806087
JAMA. 2001 May 9;285(18):2370-5
11343485
Arch Intern Med. 2009 Jun 22;169(12):1147-55
19546416
Chest. 2012 Mar;141(3):674-681
21835901
J Hypertens. 1997 Dec;15(12 Pt 2):1593-603
9488210
Heart Rhythm. 2015 Apr;12(4):818-24
25533582
Heart Rhythm. 2010 Sep;7(9):1263-70
20338265
Biol Chem. 2004 Mar-Apr;385(3-4):217-21
15134334
Heart Rhythm. 2010 Dec;7(12):1900-6
20570754
J Appl Physiol (1985). 2005 Nov;99(5):1689-96
15994246
Heart Rhythm. 2012 Mar;9(3):321-7
22016075
Eur Respir J. 2011 Jan;37(1):119-28
20525723
J Sleep Res. 2009 Jun;18(2):188-95
19645965
Adv Exp Med Biol. 2003;536:559-64
14635713
Heart Rhythm. 2012 Sep;9(9):1409-16.e1
22440155
J Am Coll Cardiol. 2014 Nov 11;64(19):2013-23
25440097
Eur Respir J. 2006 Jan;27(1):128-35
16387945
Hypertension. 2013 Oct;62(4):767-74
23959548
Am J Respir Crit Care Med. 2000 Dec;162(6):2039-42
11112110
J Clin Sleep Med. 2013 Oct 15;9(10):1003-12
24127144
Respir Res. 2006 Feb 06;7:22
16460564
Hypertension. 1992 Nov;20(5):612-9
1428112
J Physiol. 1963 Jan;165:179-97
14024792
J Sleep Res. 2007 Jun;16(2):217-25
17542952
J Hypertens. 1997 Dec;15(12 Pt 2):1613-9
9488212
Pacing Clin Electrophysiol. 2012 Aug;35(8):966-72
22671991
J Cardiovasc Electrophysiol. 2016 Sep;27(9):1086-92
27235276
J Am Coll Cardiol. 2009 Nov 24;54(22):2075-83
19926016
Am J Respir Crit Care Med. 2005 Oct 1;172(7):915-20
15976378
Am J Respir Crit Care Med. 2011 Nov 15;184(10):1192-9
21836134
J Physiol. 2006 Dec 1;577(Pt 2):705-16
16973705
J Mol Cell Cardiol. 2012 Feb;52(2):454-63
21978629
Chest. 2015 Oct;148(4):945-952
25927872
Am J Respir Crit Care Med. 2016 Apr 1;193(7):783-91
26595380
Circ Cardiovasc Imaging. 2010 May;3(3):282-9
20160141
J Am Coll Cardiol. 2013 Jul 23;62(4):300-5
23623910
Circ Arrhythm Electrophysiol. 2011 Aug;4(4):441-7
21593198
J Clin Sleep Med. 2011 Apr 15;7(2):172-8
21509332
Eur Heart J. 2017 Jan 1;38(1):38-50
27071821
Sleep. 1991 Aug;14(4):346-50
1947598
Am Heart J. 2015 May;169(5):647-654.e2
25965712
Card Electrophysiol Clin. 2011 Mar 1;3(1):23-45
21892379
Am J Cardiol. 2008 Jun 1;101(11):1663-8
18489948
Adv Exp Med Biol. 2009;648:345-9
19536498