Left Atrial Remodeling
2017; Lippincott Williams & Wilkins; Volume: 10; Issue: 2 Linguagem: Dinamarquês
10.1161/circimaging.117.006036
ISSN1942-0080
Autores Tópico(s)Cardiovascular Effects of Exercise
ResumoHomeCirculation: Cardiovascular ImagingVol. 10, No. 2Left Atrial Remodeling Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBLeft Atrial RemodelingMore Than Just Left Atrial Enlargement Brian D. Hoit, MD Brian D. HoitBrian D. Hoit From the Department of Medicine, Case Western Reserve University, Cleveland, OH; and Harrington Heart and Vascular Center, University Hospitals Cleveland Medical Center, Cleveland, OH. Originally published2 Feb 2017https://doi.org/10.1161/CIRCIMAGING.117.006036Circulation: Cardiovascular Imaging. 2017;10:e006036Form follows function—this has been misunderstood. Form and function should be one, joined in a spiritual union.—Frank Lloyd WrightLeft atrial (LA) remodeling refers to the spectrum of pathophysiological changes in atrial structure and mechanical function and the electric, ionic, and molecular milieu of the LA that most often occurs in response to stresses imposed by conditions such as hypertension, heart failure, diabetes mellitus, and obesity. Remodeling is initially adaptive, but when it occurs in response to a chronic pathological stimulus (as opposed to remodeling of the athlete's heart), it often becomes maladaptive and associated with an increased risk of cardiovascular events and mortality.1 Remodeling forms the basis of atrial cardiomyopathy, defined recently by a multisociety, expert consensus statement as any complex of structural, architectural, contractile, or electrophysiological changes affecting the atria with the potential to produce clinically relevant manifestations.2See Article by Oliver et alLA structural remodeling is the complex phenotypic expression that results from changes in LA size, shape,3 and architecture and alterations in the cardiomyocyte, fibroblast, and noncollagen infiltrative compartments of the atrium.2 LA enlargement, which is simple to measure, is the default clinical hallmark of structural remodeling that occurs most often in response to LA pressure and volume overload; in the absence of atrial fibrillation, mitral valvular disease, and high cardiac output states, it is an excellent biomarker for the presence and severity of left ventricular (LV) diastolic dysfunction.4 Moreover, LA enlargement portends a poor prognosis in a variety of cardiovascular diseases.1Indices of LA size are also markers of cardiovascular risk in the general population.5,6 The strength of the association between atrial remodeling as determined by increased maximal indexed LA volume (LAVi) and cardiovascular risk reported in the literature is influenced by the nature of the study population. Thus, in a cohort of 1160 elderly patients from Olmsted County, Minnesota, with cardiovascular disease referred for an echocardiogram, both LAVi and LV diastolic dysfunction were independently predictive of cardiovascular events.5 In contrast, in a study of 2042 randomly selected residents of Olmsted County, LAVi lost the ability to predict all-cause mortality when controlling for the degree of diastolic dysfunction, suggesting that in the general population, changes in LAVi are closely related to diastolic function and may provide no incremental prognostic benefit.6 Moreover, in a prospective study of 574 participants in Olmsted County, Minnesota, minimum LA volume (which takes into account atrial function and afterload) was superior to maximal LA volume for predicting the 3-year risk of developing first atrial fibrillation or flutter and was an independent predictor in a model that included clinical variables, body mass index, diastolic dysfunction, and maximal LA volume.7These data and others suggest that LA function (mechanical remodeling) may surpass LA size (structural remodeling) as having prognostic importance in the general population. Thus, in an unselected cohort of 2808 individuals from the Strong Heart Study with a high prevalence of obesity and diabetes mellitus, but not prevalent cardiovascular disease, LA systolic force was associated with a higher rate of combined fatal and nonfatal cardiovascular events, independent of age, risk factors, and LV geometry and diastolic dysfunction.8 Furthermore, among 1802 participants of the DHS (Dallas Heart Study) followed up for a median of 8.1 years, decreasing LA emptying fraction, but not LAVi (measured with cardiac magnetic resonance imaging [cMRI]), was independently associated with mortality and added incremental power to a predictive model consisting of Framingham risk score, diabetes mellitus, race, LV mass, and LV ejection fraction.9 In this large, ethnically diverse cohort, LAVi and LA emptying fraction were only weakly associated with one another.In this issue of Circulation: Cardiovascular Imaging, Oliver et al10 report on a cohort of 748 of the original participants in the aforementioned DHS-1 that returned an average of 8 years after their initial visit (DHS-2) to examine the associations of changes in LAVi (measured by cMRI) and traditional risk factors, blood pressure, biomarkers, LV geometry and remodeling (measured by cMRI), and global and regional adiposity (measured with dual-energy x-ray absorptiometry in visit 1 and single-slice magnetic resonance imaging in visit 2. Multivariable analysis found independent associations with a change in LAVi with (1) black and Hispanic race/ethnicity; (2) the change in systolic blood pressure; (3) LV mass and change in LV mass (driven by LV volume, not by wall thickness); (4) NT-pro-BNP and change in NT-pro-BNP; and (5) body mass index (driven by associations with visceral fat, not by associations with subcutaneous or lower body fat). The authors suggest that LA enlargement may be mediated by blood pressure control and the development of visceral adiposity. Many of the independent determinants of LA enlargement during the follow-up period are not surprising in view of the associations reported earlier in the original cohort.9 However, the study is unique in that LA size was examined longitudinally in a large multiethnic, carefully characterized population using an interesting statistical approach—ie, quartile and multivariable linear regression analyses of the second measurement using the first (baseline) as a covariate.The authors acknowledge several limitations, many of which are understandable considering the scope and complexity of the study. Although mentioned in passing, it is important to consider the potential role of selection bias, as participants had to be willing and able (ie, alive), with neither incident nor prevalent cardiovascular disease, all of which may explain the low number (12) of events. Reflecting the low risk, few of the participants would have been considered to have LA enlargement using the common cMRI LAVi partition value of 53 mL/m211; whether the change in LA volume (not clinically significant until quartile 4) would translate into an independent increase in events is highly unlikely considering the results in the original cohort.9 Test–test variability analysis might have been a valuable addition to calibrate the importance of a change in LA volume between the 2 studies. In addition, differences in cMRI acquisition (prospective gating that results in smaller volumes in DHS-1, retrospective gating in DHS-2) may have exaggerated the change in LAVi. In view of these considerations, it is reasonable to ask whether the change in LAVi actually represents structural remodeling; additional studies with cMRI might have been useful in this regard. For example, late gadolinium–detected and postcontrast T1 mapping–detected atrial fibrosis may have identified early (subclinical) structural remodeling.1 In addition, volumetric assessment of LA function (LA emptying fraction or even LA minimum volume) or feature tracking cMRI-strain would have been informative.An important finding of this study and consistent with existing literature12–15 is that increased fat mass (but not lean mass) as demonstrated by dual-energy x-ray absorptiometry and magnetic resonance imaging could explain the relation between body mass index and LA size. In a large, older aged, biracial cohort (Atherosclerosis Risk in Communities study), increasing body mass index, waist circumference, and body fat were associated with allometrically indexed LAV,12 and at the 25-year examination in 2547 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults), who were not obese at baseline, more overall and abdominal adiposity was associated with an increased LA dimension.13 Finally, body fat composition has been shown to be independently associated with increased LA dimension, particularly in women with increased inflammation.14 Important variables not measured in DHS-2 include dual-energy x-ray absorptiometry measurement of body fat distribution and adiponectin, which has been shown to be inversely related to LA size independent of age, sex, insulin resistance, and LV mass.15 The relation to fat is particularly relevant in view of studies that have shown reverse atrial remodeling (structural, functional, and electrophysiological) with weight loss because of diet and lifestyle16 and laparoscopic sleeve gastrectomy.17The article by Oliver et al is a good hypothesis-generating study that raises many important questions. What threshold of a change in LAVi constitutes remodeling? Reverse remodeling? All of quartile 1 participants and some in quartile 2 had a decrease in LAVi over 8 years; what variables were associated with this reverse remodeling? Data from the diet/bypass cohorts,16,17 inhibition of the renin–angiotensin–aldosterone axis,18 blood pressure reduction after renal denervation,19 and after correction of mitral valve disease20 have resulted in reverse atrial mechanical and electric remodeling, in addition to a reduction in LA size. Importantly, although reverse remodeling in response to an intervention has been shown to occur at multiple hierarchical levels, the impact on clinical outcomes is unclear.Clearly, atrial remodeling is more than simply a change in LA size. Indeed, atrial enlargement, particularly if the volume falls within limits of normality, is neither necessary nor sufficient for remodeling to be considered present. In that case, a measure of atrial mechanical or electrophysiological function is essential. Echocardiographic, cMRI, and electroanatomic techniques should be used and cardiovascular outcomes measured if we truly wish to gauge the impact of a pathophysiological stimulus on LA remodeling and an intervention on reverse atrial remodeling. Form does not necessarily follow function, but they should, as Wright noted in architecture, be thought of as one.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Brian D. Hoit, MD, Harrington Heart and Vascular Center, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland OH 44106. E-mail [email protected]References1. Hoit BD. Left atrial size and function: role in prognosis.J Am Coll Cardiol. 2014; 63:493–505. doi: 10.1016/j.jacc.2013.10.055.CrossrefMedlineGoogle Scholar2. Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen SA, Chugh SS, Corradi D, D'Avila A, Dobrev D, Fenelon G, Gonzalez M, Hatem SN, Helm R, Hindricks G, Ho SY, Hoit B, Jalife J, Kim YH, Lip GY, Ma CS, Marcus GM, Murray K, Nogami A, Sanders P, Uribe W, Van Wagoner DR, Nattel S. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.Heart Rhythm. 2017; 14:e3–e40. doi: 10.1016/j.hrthm.2016.05.028.CrossrefMedlineGoogle Scholar3. Bisbal F, Gómez-Pulido F, Cabanas-Grandío P, Akoum N, Calvo M, Andreu D, Prat-González S, Perea RJ, Villuendas R, Berruezo A, Sitges M, Bayés-Genís A, Brugada J, Marrouche NF, Mont L. Left atrial geometry improves risk prediction of thromboembolic events in patients with atrial fibrillation.J Cardiovasc Electrophysiol. 2016; 27:804–810. doi: 10.1111/jce.12978.CrossrefMedlineGoogle Scholar4. Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden.Am J Cardiol. 2002; 90:1284–1289.CrossrefMedlineGoogle Scholar5. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, Seward JB. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography.J Am Coll Cardiol. 2003; 42:1199–1205.CrossrefMedlineGoogle Scholar6. Pritchett AM, Mahoney DW, Jacobsen SJ, Rodeheffer RJ, Karon BL, Redfield MM. Diastolic dysfunction and left atrial volume: a population-based study.J Am Coll Cardiol. 2005; 45:87–92. doi: 10.1016/j.jacc.2004.09.054.CrossrefMedlineGoogle Scholar7. Fatema K, Barnes ME, Bailey KR, Abhayaratna WP, Cha S, Seward JB, Tsang TS. Minimum vs. maximum left atrial volume for prediction of first atrial fibrillation or flutter in an elderly cohort: a prospective study.Eur J Echocardiogr. 2009; 10:282–286. doi: 10.1093/ejechocard/jen235.CrossrefMedlineGoogle Scholar8. Chinali M, de Simone G, Roman MJ, Bella JN, Liu JE, Lee ET, Best LG, Howard BV, Devereux RB. Left atrial systolic force and cardiovascular outcome. The Strong Heart Study.Am J Hypertens. 2005; 18(12pt 1):1570–1576; discussion 1577. doi: 10.1016/j.amjhyper.2005.05.036.CrossrefMedlineGoogle Scholar9. Gupta S, Matulevicius SA, Ayers CR, Berry JD, Patel PC, Markham DW, Levine BD, Chin KM, de Lemos JA, Peshock RM, Drazner MH. Left atrial structure and function and clinical outcomes in the general population.Eur Heart J. 2013; 34:278–285. doi: 10.1093/eurheartj/ehs188.CrossrefMedlineGoogle Scholar10. Oliver W, Matthews G, Ayers CR, Garg S,, Gupta S, Neeland IJ, Drazner MH, Berry JD, Matulevicius S, de Lemos JA. Factors associated with left atrial remodeling in the general population.Circ Cardiovasc Imaging. 2017; 10:e005047. doi: 10.1161/CIRCIMAGING.116.005047.LinkGoogle Scholar11. Maceira AM, Cosín-Sales J, Roughton M, Prasad SK, Pennell DJ. Reference left atrial dimensions and volumes by steady state free precession cardiovascular magnetic resonance.J Cardiovasc Magn Reson. 2010; 12:65. doi: 10.1186/1532-429X-12-65.CrossrefMedlineGoogle Scholar12. Bello NA, Cheng S, Claggett B, Shah AM, Ndumele CE, Roca GQ, Santos AB, Gupta D, Vardeny O, Aguilar D, Folsom AR, Butler KR, Kitzman DW, Coresh J, Solomon SD. Association of weight and body composition on cardiac structure and function in the ARIC study (Atherosclerosis Risk in Communities).Circ Heart Fail. 2016; 9:e002978. doi: 10.1161/CIRCHEARTFAILURE.115.002978.LinkGoogle Scholar13. Reis JP, Allen N, Gibbs BB, Gidding SS, Lee JM, Lewis CE, Lima J, Lloyd-Jones D, Loria CM, Powell-Wiley TM, Sharma S, Wei G, Liu K. Association of the degree of adiposity and duration of obesity with measures of cardiac structure and function: the CARDIA study.Obesity (Silver Spring). 2014; 22:2434–2440. doi: 10.1002/oby.20865.CrossrefMedlineGoogle Scholar14. Lai YH, Liu CC, Kuo JY, Hung TC, Wu YJ, Yeh HI, Bulwer BE, Hung CL. Independent effects of body fat and inflammatory markers on ventricular geometry, midwall function, and atrial remodeling.Clin Cardiol. 2014; 37:172–177. doi: 10.1002/clc.22242.CrossrefMedlineGoogle Scholar15. Ybarra J, Resmini E, Planas F, Navarro-López F, Webb S, Pou JM, Santos A, Ballesta-López C. Relationship between adiponectin and left atrium size in uncomplicated obese patients: adiponectin, a link between fat and heart.Obes Surg. 2009; 19:1324–1332. doi: 10.1007/s11695-009-9924-5.CrossrefMedlineGoogle Scholar16. 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.CrossrefMedlineGoogle Scholar17. Tuluce K, Kara C, Tuluce SY, Cetin N, Topaloglu C, Bozakaya YT, Saklamaz A, Cinar CS, Ergene O. Early reverse cardiac remodeling effect of laparoscopic sleeve gastrectomy.Obes Surg. 2016; 27:364–375. doi: 10:1007/s11695-016-2301-2CrossrefGoogle Scholar18. Masaki M, Mano T, Eguchi A, Fujiwara S, Sugahara M, Hirotani S, Tsujino T, Komamura K, Koshiba M, Masuyama T. Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.Heart Vessels. 2016; 31:1826–1833. doi: 10.1007/s00380-016-0796-z.CrossrefMedlineGoogle Scholar19. McLellan AJ, Schlaich MP, Taylor AJ, Prabhu S, Hering D, Hammond L, Marusic P, Duval J, Sata Y, Ellims A, Esler M, Peter K, Shaw J, Walton A, Kalman JM, Kistler PM. Reverse cardiac remodeling after renal denervation: atrial electrophysiologic and structural changes associated with blood pressure lowering.Heart Rhythm. 2015; 12:982–990. doi: 10.1016/j.hrthm.2015.01.039.CrossrefMedlineGoogle Scholar20. Candan O, Ozdemir N, Aung SM, Hatipoglu S, Karabay CY, Guler A, Gecmen C, Dogan C, Omaygenc O, Bakal RB. Atrial longitudinal strain parameters predict left atrial reverse remodeling after mitral valve surgery: a speckle tracking echocardiography study.Int J Cardiovasc Imaging. 2014; 30:1049–1056. doi: 10.1007/s10554-014-0433-9.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails February 2017Vol 10, Issue 2 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.117.006036PMID: 28153950 Originally publishedFebruary 2, 2017 KeywordsEditorialshypertensionbiomarkerfibroblastadiposityobesityPDF download Advertisement SubjectsMagnetic Resonance Imaging (MRI)Race and Ethnicity
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