Background Left atrial appendage (LAA) volume has been shown to be increased in patients with acute cryptogenic stroke. Atrial fibrillation (AF) is a well-recognized risk factor but it is not the only one associated with LAA enlargement. The aim of the study was to clarify the multifactorial etiology of LAA enlargement in cardiogenic stroke/TIA patients without AF. Methods Altogether 149 patients with suspected cardioembolic stroke/TIA (47 females; mean age 61 years) underwent cardiac CT. Diagnosed AF on admittance was an exclusion criteria but 24-hour Holter ambulatory ECG revealed paroxysmal AF (PAF) in 20 patients. Body surface area adjusted LAA volume was evaluated. Eighteen different variables were registered including general characteristics, definite and potential causal risk factors for ischemic stroke/TIA, clinical echoparameters and CT based cardiac volumetric and adipose tissue measurements. A stepwise linear regression analysis was performed to achieve a model adjusted for the number of predictors of LAA volume increase. Results In linear regression analysis, the best model accounted for 30% of the variability in LAA volume, including PAF (19%) and enlarged left atrial volume (6%), enlarged left ventricle end-systolic diameter (3%) and decreased pericardial adipose tissue (2%). No multi-colinearity between variables was observed. In addition to PAF, no other definitive or potential causal risk factors could account for the LAA volume in these patients. Conclusions LAA volume increase seems to be poorly associated with currently known stroke/TIA risk factors, except for AF. Targeting more comprehensive ECG monitoring for stroke patients with increased LAA volume should be considered.
References
[1]
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al. (2010) Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation 121: 46–215. doi: 10.1161/circulationaha.109.192667
[2]
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, et al. (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24: 35–41. doi: 10.1161/01.str.24.1.35
[3]
Rodríguez-Yá?ez M, Arias-Rivas S, Santamaría-Cadavid M, Sobrino T, Castillo J, et al. (2013) High pro-BNP levels predict the occurrence of atrial fibrillation after cryptogenic stroke. Neurology 81: 444–447. doi: 10.1212/wnl.0b013e31829d8773
[4]
Jickling GC, Stamova B, Ander BP, Zhan X, Liu D, et al. (2012) Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location. Stroke 43: 2036–2041. doi: 10.1161/strokeaha.111.648725
[5]
Taina M, Vanninen R, Hedman M, J?k?l? P, K?rkk?inen S, et al. (2013) Left Atrial Appendage Volume Increased in More than Half of Patients with Cryptogenic Stroke. PLOS One 2013 8(11): e79519 doi:10.1371/journal.pone.0079519.
[6]
Therkelsen SK, Groenning BA, Svendsen JH, Jensen GB (2005) Atrial and ventricular volume and function in persistent and permanent atrial fibrillation, a magnetic resonance imaging study. J Cardiovasc Magn Reson 7: 465–473. doi: 10.1081/jcmr-200053618
[7]
Beinart R, Heist EK, Newell JB, Holmvang G, Ruskin JN, et al. (2011) Left atrial appendage dimensions predict the risk of stroke/TIA in patients with atrial fibrillation. J Cardiovasc Electrophysiol. 22: 10–15. doi: 10.1111/j.1540-8167.2010.01854.x
[8]
Okuyama H, Hirono O, Liu L, Takeishi Y, Kayama T, et al. (2006) Higher levels of serum fibrin-monomer reflect hypercoagulable state and thrombus formation in the left atrial appendage in patients with acute ischemic stroke. Circ J 70: 971–976. doi: 10.1253/circj.70.971
[9]
Walker DT, Humphries JA, Phillips KP (2012) Anatomical analysis of the left atrial appendage using segmented, three-dimensional cardiac CT: A comparison of patients with paroxysmal and persistent forms of atrial fibrillation. J Interv Card Electrophysiol 34: 173–179. doi: 10.1007/s10840-011-9638-1
[10]
Nucifora G, Faletra FF, Regoli F, Pasotti E, Pedrazzini G, et al. (2011) Evaluation of the left atrial appendage with real-time 3-dimensional transesophageal echocardiography: implications for catheter-based left atrial appendage closure. Circ Cardiovasc Imaging 4: 514–523. doi: 10.1161/circimaging.111.963892
[11]
Mosteller RD (1987) Simplified calculation of body-surface area. N Engl J Med 317: 1098. doi: 10.1056/nejm198710223171717
[12]
Sipola P, Hedman M, Onatsu J, Turpeinen A, Halinen M, et al. (2013) Computed tomography and echocardiography together reveal more high-risk findings than echocardiography alone in the diagnostics of stroke etiology. Cerebrovasc Dis 35: 521–530. doi: 10.1159/000350734
[13]
Lawes CMM, Bennett DA, Feigin VL, Rodgers A (2004) Blood pressure and stroke: an overview of published reviews. Stroke 35: 776–785. doi: 10.1161/01.str.0000116869.64771.5a
[14]
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, et al. (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 366: 1267–1278. doi: 10.1016/s0140-6736(05)67394-1
[15]
Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, et al. (2003) Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 361: 107–116. doi: 10.1016/s0140-6736(03)12228-3
[16]
Halliday A, Mansfield A, Marro J, Peto C, Peto R, et al. (2004) Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 363: 1491–1502. doi: 10.1016/s0140-6736(04)16146-1
[17]
Hart RG, Benavente O, McBride R, Pearce LA (1999) Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 131: 492–501. doi: 10.7326/0003-4819-131-7-199910050-00003
[18]
Bonita R, Duncan J, Truelson T, Jackson R, Beaglehole R (1999) Passive smoking as well as active smoking increases the risk of stroke. Tobacco Control 8: 156–160. doi: 10.1136/tc.8.2.156
[19]
Asia Pacific Cohort Studies Collaboration (2004) Blood glucose and risk of cardiovascular disease in the Asia Pacific region. Diabetes Care 27: 2836–2842. doi: 10.2337/diacare.27.12.2836
[20]
Loh E, Sutton MS, Wun CC, Rouleau JL, Flaker GC, et al. (1997) Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 336: 251–257. doi: 10.1056/nejm199701233360403
[21]
Coulshed N, Epstein EJ, McKendrick CS, Galloway RW, Walker E (1970) Systemic embolism in mitral valve disease. BMJ 32: 26–34. doi: 10.1136/hrt.32.1.26
[22]
Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, et al. (2005) Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke 36: 2533–2537. doi: 10.1161/01.str.0000190005.09442.ad
[23]
Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, et al. (2005) Recommendations for Chamber Quantification: A Report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, Developed in Conjunction with the European Association of Echocardiography, a Branch of the European Society of Cardiology. J Am Soc Echocardiogr 18: 1440–1463. doi: 10.1016/j.echo.2005.10.005
[24]
DiTomasso D, Carnethon MR, Wright CM, Allison MA (2010) The association between visceral fat and calcified atherosclerosis are stronger in women than men. Atherosclerosis 208: 531–536. doi: 10.1016/j.atherosclerosis.2009.08.015
[25]
Graham TP Jr, Jarmakani JM, Atwood GF, Canent RV Jr (1973) Right ventricular volume determinations in children. Normal values and observations with volume or pressure overload. Circulation 47: 144–153. doi: 10.1161/01.cir.47.1.144
[26]
Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, et al. (2012) Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 366: 120–129. doi: 10.1056/nejmoa1105575
[27]
Anselmino M, Blandino A, Beninati S, Rovera C, Boffano C, et al. (2011) Morphologic analysis of left atrial anatomy by magnetic resonance angiography in patients with atrial fibrillation: a large single center experience. J Cardiovasc Electrophysiol 22: 1–7. doi: 10.1111/j.1540-8167.2010.01853.x
[28]
Di Tullio MR, Sacco RL, Sciacca RR, Homma S (1999) Left atrial size and the risk of ischemic stroke in an ethnically mixed population. Stroke 30: 2019–2024. doi: 10.1161/01.str.30.10.2019
[29]
Heist EK, Refaat M, Danik SB, Holmvang G, Ruskin JN, et al. (2006) Analysis of the left atrial appendage by magnetic resonance angiography in patients with atrial fibrillation. Heart Rhythm 3: 1313–1318. doi: 10.1016/j.hrthm.2006.07.022
[30]
Langman J. Cardiovascular System. In: Langman J, Sadler TW (2003) Langman’s Medical Embryology. 9th Revised Edition, New York, NY: Lippincott Williams and Wilkins: 223–274.
[31]
Ito T, Suwa M, Kobashi A, Yagi H, Hirota Y, et al. (1998) Influence of Altered Loading Conditions on Left Atrial Appendage Function In Vivo. Am J Cardiol. 81: 1056–1059. doi: 10.1016/s0002-9149(98)00011-3
[32]
Miller JT, O’Rourke RA, Crawford MH (1988) Left atrial enlargement: an early sign of hypertensive heart disease. Am Heart J 116: 1048–1051. doi: 10.1016/0002-8703(88)90158-5
[33]
Frohlich ED, Apstein C, Chobanian AV, Devereux RB, Dustan HP (1992) The heart in hypertension. N Engl J Med 327: 998–1008. doi: 10.1056/nejm199210013271406
[34]
Benjamin EJ, D’Agostino RB, Belanger AJ, Wolf PA, Levy D (1995) Left Atrial Size and the Risk of Stroke and Death. The Framingham Heart Study. Circulation 92: 835–841. doi: 10.1161/01.cir.92.4.835
[35]
Bakalli A, Georgievska-Ismail L, Ko?inaj D, Musliu N, Krasniqi A, et al. (2013) Prevalence of left chamber cardiac thrombi in patients with dilated left ventricle at sinus rhythm: the role of transesophageal echocardiography. J Clin Ultrasound 41: 38–45. doi: 10.1002/jcu.21953
[36]
Agmon Y, Khandheria BK, Gentile F, Seward JB (2002) Clinical and echocardiographic characteristics of patients with left atrial thrombus and sinus rhythm: experience in 20 643 consecutive transesophageal echocardiographic examinations. Circulation 105: 27–31. doi: 10.1161/hc0102.101776
[37]
Handke M, Harloff A, Hetzel A, Olschewski M, Bode C, et al. (2005) Predictors of left atrial spontaneous echocardiographic contrast or thrombus formation in stroke patients with sinus rhythm and reduced left ventricular function. Am J Cardiol 96: 1342–1344. doi: 10.1016/j.amjcard.2005.06.085
[38]
Mahilmaran A, Nayar PG, Sudarsana G, Abraham K (2004) Relationship of left atrial appendage function to left ventricular function. Indian Heart J 56: 293–298.
[39]
Pollick C, Taylor D (1991) Assessment of left atrial appendage function by transesophageal echocardiography. Implications for the development of thrombus. Circulation 84: 223–231. doi: 10.1161/01.cir.84.1.223
[40]
Ozer N, Kili? H, Arslan U, Atalar E, Aks?yek S, et al. (2005) Echocardiographic predictors of left atrial appendage spontaneous echocontrast in patients with stroke and atrial fibrillation. J Am Soc Echocardiogr 18: 1362–1365. doi: 10.1016/j.echo.2005.03.023
[41]
Fox CS, Gona P, Hoffmann U, Porter SA, Salton CJ, et al. (2009) Pericardial fat, intrathoracic fat, and measures of left ventricular structure and function: the Framingham Heart Study. Circulation 119: 1586–1591. doi: 10.1161/circulationaha.108.828970
[42]
Thanassoulis G, Massaro JM, O’Donnell CJ, Hoffmann U, Levy D, et al. (2010) Pericardial fat is associated with prevalent atrial fibrillation: the Framingham Heart Study. Circ Arrhythm Electrophysiol 2010 3: 345–350. doi: 10.1161/circep.109.912055
[43]
Wong CX, Abed HS, Molaee P, Nelson AJ, Brooks AG, et al. (2011) Pericardial fat is associated with atrial fibrillation severity and ablation outcome. J Am Coll Cardiol 57: 1745–1751. doi: 10.1016/j.jacc.2010.11.045
[44]
Greif M, von Ziegler F, Wakili R, Tittus J, Becker C, et al. (2013) Increased pericardial adipose tissue is correlated with atrial fibrillation and left atrial dilatation. Clin Res Cardiol 102: 555–562. doi: 10.1007/s00392-013-0566-1