Why the study?
Does aging affect left atrial compliance and electromechanical properties in subjects without structural heart disease?
Observational (n=386)
Does aging affect left atrial compliance and electromechanical properties in subjects without structural heart disease?
Effect estimate: PWD β=0.161, PA-TDI β=0.476, LA strain β=-0.259
p-value: p=<0.001
Aging is independently associated with prolonged atrial conduction time and reduced left atrial compliance in patients without structural heart disease, with effects further modulated by obesity and LA volume.
May indicate subclinical atrial remodeling with aging; leaves open causal links to arrhythmias and need for prospective validation.
Aging is associated with changes in left atrial (LA) structure and function. The present study aimed at describing the effect of aging on LA properties in a large cohort of subjects without structural heart disease. We divided 386 subjects (mean age 58 years [range 16 to 91]; 188 men [49%]) clinically referred for echocardiography according to age groups. The P-wave dispersion (PWD), reflecting total atrial conduction time, was measured on a 12-lead surface electrocardiogram as the difference between maximum and minimum P-wave duration. The PA-TDI duration reflecting the total atrial conduction time was measured on tissue Doppler imaging (TDI) as the time between onset of P wave on surface electrocardiogram to peak A′-wave velocity. Two-dimensional speckle-tracking echocardiography was used to assess LA reservoir function, reflecting LA compliance. In the overall population, mean PWD, PA-TDI, and LA reservoir strain were 43 ± 12 ms, 129 ± 27 ms, and 36 ± 13%, respectively. Increasing age was independently associated with prolonged PWD (β = 0.161; p <0.001), PA-TDI (β = 0.476; p <0.001), and reduced LA reservoir strain (β = −0.259; <0.001), suggesting age-related fibrotic changes of the LA myocardium. The association between age and LA reservoir strain was modulated by body mass index (β = −0.582; p <0.001) and LA volume index (β = −0.117; p = 0.014). In conclusion, aging is associated with longer PWD and PA-TDI duration along with a decrease in LA reservoir function. Obesity and larger LA volumes are independently associated with reduced LA compliance. Aging is associated with changes in left atrial (LA) structure and function. The present study aimed at describing the effect of aging on LA properties in a large cohort of subjects without structural heart disease. We divided 386 subjects (mean age 58 years [range 16 to 91]; 188 men [49%]) clinically referred for echocardiography according to age groups. The P-wave dispersion (PWD), reflecting total atrial conduction time, was measured on a 12-lead surface electrocardiogram as the difference between maximum and minimum P-wave duration. The PA-TDI duration reflecting the total atrial conduction time was measured on tissue Doppler imaging (TDI) as the time between onset of P wave on surface electrocardiogram to peak A′-wave velocity. Two-dimensional speckle-tracking echocardiography was used to assess LA reservoir function, reflecting LA compliance. In the overall population, mean PWD, PA-TDI, and LA reservoir strain were 43 ± 12 ms, 129 ± 27 ms, and 36 ± 13%, respectively. Increasing age was independently associated with prolonged PWD (β = 0.161; p <0.001), PA-TDI (β = 0.476; p <0.001), and reduced LA reservoir strain (β = −0.259; <0.001), suggesting age-related fibrotic changes of the LA myocardium. The association between age and LA reservoir strain was modulated by body mass index (β = −0.582; p <0.001) and LA volume index (β = −0.117; p = 0.014). In conclusion, aging is associated with longer PWD and PA-TDI duration along with a decrease in LA reservoir function. Obesity and larger LA volumes are independently associated with reduced LA compliance. Aging has been associated with structural changes of the left atrium (LA). Besides LA dilation as a marker of chronic left ventricular (LV) diastolic dysfunction,1Boyd A.C. Schiller N.B. Leung D. Ross D.L. Thomas L. Atrial dilation and altered function are mediated by age and diastolic function but not before the eighth decade.JACC Cardiovasc Imaging. 2011; 4: 234-242Crossref PubMed Scopus (66) Google Scholar, 2Thomas L. Levett K. Boyd A. Leung D.Y. Schiller N.B. Ross D.L. Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable?.J Am Coll Cardiol. 2002; 40: 1630-1635Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 3Sun J.P. Yang Y. Guo R. Wang D. Lee A.P. Wang X.Y. Lam Y.Y. Fang F. Yang X.S. Yu C.M. Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: normal values and effects of aging in a large group of normal subjects.Int J Cardiol. 2013; 168: 3473-3479Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar increase in LA myocardial fibrosis has been demonstrated and associated with impaired LA function, increase in LA stiffness, and changes in LA electrophysiological properties.3Sun J.P. Yang Y. Guo R. Wang D. Lee A.P. Wang X.Y. Lam Y.Y. Fang F. Yang X.S. Yu C.M. Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: normal values and effects of aging in a large group of normal subjects.Int J Cardiol. 2013; 168: 3473-3479Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 4Kistler P.M. Sanders P. Fynn S.P. Stevenson I.H. Spence S.J. Vohra J.K. Sparks P.B. Kalman J.M. Electrophysiologic and electroanatomic changes in the human atrium associated with age.J Am Coll Cardiol. 2004; 44: 109-116Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar, 5Evin M. Redheuil A. Soulat G. Perdrix L. Ashrafpoor G. Giron A. Lamy J. Defrance C. Roux C. Hatem S.N. Diebold B. Mousseaux E. Kachenoura N. Left atrial aging: a cardiac magnetic resonance feature-tracking study.Am J Physiol Heart Circ Physiol. 2016; 310: H542-H549Crossref PubMed Scopus (33) Google Scholar These structural and functional LA changes have been associated with increased risk of atrial fibrillation and heart failure.6Blume G.G. McLeod C.J. Barnes M.E. Seward J.B. Pellikka P.A. Bastiansen P.M. Tsang T.S. Left atrial function: physiology, assessment, and clinical implications.Eur J Echocardiogr. 2011; 12: 421-430Crossref PubMed Scopus (308) Google Scholar P-wave indexes, such as P-wave duration and P-wave dispersion (PWD), indirectly reflect the total conduction time of the LA.7Dilaveris P. Batchvarov V. Gialafos J. Malik M. Comparison of different methods for manual P wave duration measurement in 12-lead electrocardiograms.Pacing Clin Electrophysiol. 1999; 22: 1532-1538Crossref PubMed Scopus (99) Google Scholar Echocardiographic tissue Doppler imaging (TDI) also permits evaluation of the total atrial conduction time (PA-TDI duration), which reflects the extent of both electrical and structural remodeling of the atria.8Merckx K.L. De Vos C.B. Palmans A. Habets J. Cheriex E.C. Crijns H.J. Tieleman R.G. Atrial activation time determined by transthoracic Doppler tissue imaging can be used as an estimate of the total duration of atrial electrical activation.J Am Soc Echocardiogr. 2005; 18: 940-944Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar Additionally, 2-dimensional (2D) speckle-tracking echocardiography enables the assessment of LA reservoir strain, a marker of LA compliance.9Rosca M. Lancellotti P. Popescu B.A. Pierard L.A. Left atrial function: pathophysiology, echocardiographic assessment, and clinical applications.Heart. 2011; 97: 1982-1989Crossref PubMed Scopus (166) Google Scholar PWD, PA-TDI, and LA reservoir strain may change with aging because of structural remodeling of the LA. The present study aimed at describing the effect of aging on LA properties in a cohort of subjects without structural heart disease. A total of 386 patients who were clinically referred for cardiac evaluation and transthoracic echocardiography at the Leiden University Medical Center (The Netherlands) without structural heart disease were evaluated retrospectively.10Lang R.M. Badano L.P. Mor-Avi V. Afilalo J. Armstrong A. Ernande L. Flachskampf F.A. Foster E. Goldstein S.A. Kuznetsova T. Lancellotti P. Muraru D. Picard M.H. Rietzschel E.R. Rudski L. Spencer K.T. Tsang W. Voigt J.U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16: 233-270Crossref PubMed Scopus (4274) Google Scholar, 11Lancellotti P. Tribouilloy C. Hagendorff A. Popescu B.A. Edvardsen T. Pierard L.A. Badano L. Zamorano J.L. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2013; 14: 611-644Crossref PubMed Scopus (1085) Google Scholar Referral reasons included evaluation of dyspnea, chest pain, screening preceding noncardiac intervention, palpitations, and evaluation of patients with high cardiovascular risk profile. Subjects with previous cardiac intervention, known history of coronary artery disease, pacemaker implantation, documented cardiac arrhythmias, LV wall motion abnormalities at rest, and any grade of valvular stenosis or more than mild valvular regurgitation were excluded. Therefore, only patients with structurally and functionally normal hearts on echocardiography and sinus rhythm on the electrocardiogram (ECG) without conduction abnormalities were included in the present evaluation. Patients were selected to obtain approximately equal proportions of gender-matched groups across 5 pre-determined age categories: <45, 45 to 54, 55 to 64, 65 to 74, and >75 years. Patient demographics and clinical data were collected. Medications including angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, β blockers, statins, diuretics, and calcium channel blockers were noted. All clinical data were stored at the departmental Cardiology Information System (EZIS chipsoft and EPD-Vision, Leiden University Medical Center). The Dutch Central Committee on Human-Related Research (CCMO) allows the use of anonymous data without previous approval of an institutional review board provided that the data are acquired for routine patient care. All data used for this study were acquired for clinical purposes and handled anonymously. The standard 12-lead ECG was recorded at 100 mm/s paper speed and 40 mm/mV calibration. Customized software was used to analyze the PWD (Megacare Infinity VF4; Dräger Medical, Danvers, Massachusetts). PWD was defined as the time difference between maximum P-wave duration and minimum P-wave duration measured in any lead (Figure 1). The onset and end of the P wave were defined as the point of the first visible upward slope from the isoelectric line and the point of return to isoelectric line, respectively. QT interval was corrected for heart rate using the Bazett formula: QTc = QT/√R−R.12Funck-Brentano C. Jaillon P. Rate-corrected QT interval: techniques and limitations.Am J Cardiol. 1993; 72: 17b-22bAbstract Full Text PDF PubMed Scopus (346) Google Scholar Echocardiographic data were obtained with patients at rest in the left lateral decubitus position using commercially available ultrasound systems (Vivid 7 and E9; General Electric Vingmed, Horten, Norway). Data acquisition was performed with a 3.5-MHz or M5S transducers. Standard M-mode, 2D, color, pulsed, and continuous-wave Doppler data were acquired and stored digitally for subsequent offline analysis (EchoPac BT13; GE Medical Systems, Horten, Norway). Left ventricular ejection fraction was calculated using the Simpson's biplane method.10Lang R.M. Badano L.P. Mor-Avi V. Afilalo J. Armstrong A. Ernande L. Flachskampf F.A. Foster E. Goldstein S.A. Kuznetsova T. Lancellotti P. Muraru D. Picard M.H. Rietzschel E.R. Rudski L. Spencer K.T. Tsang W. Voigt J.U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16: 233-270Crossref PubMed Scopus (4274) Google Scholar LV mass was calculated according to Devereux et al and indexed for body surface area.10Lang R.M. Badano L.P. Mor-Avi V. Afilalo J. Armstrong A. Ernande L. Flachskampf F.A. Foster E. Goldstein S.A. Kuznetsova T. Lancellotti P. Muraru D. Picard M.H. Rietzschel E.R. Rudski L. Spencer K.T. Tsang W. Voigt J.U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16: 233-270Crossref PubMed Scopus (4274) Google Scholar Diastolic function was measured according to contemporary guidelines.13Nagueh S.F. Smiseth O.A. Appleton C.P. Byrd III, B.F. Dokainish H. Edvardsen T. Flachskampf F.A. Gillebert T.C. Klein A.L. Lancellotti P. Marino P. Oh J.K. Alexandru Popescu B. Waggoner A.D. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2016; 17: 1321-1360Crossref PubMed Scopus (1347) Google Scholar Valvular morphology and function were with 2D, color, pulsed, and continuous-wave Doppler P. Tribouilloy C. Hagendorff A. Popescu B.A. Edvardsen T. Pierard L.A. Badano L. Zamorano J.L. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2013; 14: 611-644Crossref PubMed Scopus (1085) Google Scholar data of the LA were obtained from the to the PA-TDI an echocardiographic the total atrial conduction time marker of atrial assess the PA-TDI a of was on the LA lateral wall the to obtain the time velocity of the LA The time interval between the onset of the P wave in lead II of the surface ECG and the peak on defined the PA-TDI (Figure K.L. De Vos C.B. Palmans A. Habets J. Cheriex E.C. Crijns H.J. Tieleman R.G. Atrial activation time determined by transthoracic Doppler tissue imaging can be used as an estimate of the total duration of atrial electrical activation.J Am Soc Echocardiogr. 2005; 18: 940-944Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar LA reservoir strain was evaluated using on the The ECG was to the onset of the or the and the of was to the LA wall LA reservoir strain was measured as the peak strain ventricular (Figure V. R.M. Badano L.P. M. G. M. T. 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Yang Y. Guo R. Wang D. Lee A.P. Wang X.Y. Lam Y.Y. Fang F. Yang X.S. Yu C.M. Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: normal values and effects of aging in a large group of normal subjects.Int J Cardiol. 2013; 168: 3473-3479Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 4Kistler P.M. Sanders P. Fynn S.P. Stevenson I.H. Spence S.J. Vohra J.K. Sparks P.B. Kalman J.M. Electrophysiologic and electroanatomic changes in the human atrium associated with age.J Am Coll Cardiol. 2004; 44: 109-116Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar, 5Evin M. Redheuil A. Soulat G. Perdrix L. Ashrafpoor G. Giron A. Lamy J. Defrance C. Roux C. Hatem S.N. Diebold B. Mousseaux E. Kachenoura N. Left atrial aging: a cardiac magnetic resonance feature-tracking study.Am J Physiol Heart Circ Physiol. 2016; 310: H542-H549Crossref PubMed Scopus (33) Google Scholar structural remodeling may and the for the of atrial fibrillation or lead to heart failure.6Blume G.G. McLeod C.J. Barnes M.E. Seward J.B. Pellikka P.A. Bastiansen P.M. Tsang T.S. Left atrial function: physiology, assessment, and clinical implications.Eur J Echocardiogr. 2011; 12: 421-430Crossref PubMed Scopus (308) Google Scholar, P. T.S. P.A. P. changes in a to of atrial 2005; PubMed Scopus Google Scholar between and LA structural remodeling is imaging techniques evaluation of LA and and LA myocardial tissue LA and the of fibrosis on magnetic resonance imaging are the of LA structural N. S.N. M. J. C.J. D. and quantification of left atrial structural remodeling with magnetic resonance imaging in patients with atrial PubMed Scopus Google Scholar dilation of the LA is and not in and of fibrosis with magnetic resonance high in acquisition and and The present study that the LA structural remodeling properties of the LA wall and evaluated the age-related changes of and The increased and myocardial fibrosis of the LA associated with aging lead to conduction of the which is by of the PWD on ECG and PA-TDI duration on In this increased myocardial fibrosis may in reduced LA which is by reduced LA reservoir strain on is the of PWD, PA-TDI, and LA reservoir strain for risk of patients with cardiovascular values normal LA properties have not been Data from the Heart including patients between and a PWD of to 43 S.A. P-wave of values from the Heart PubMed Scopus Google Scholar In a including with a total of between and 45 years a mean of PWD of ± of P-wave dispersion values in the of clinical 17: PubMed Scopus Google Scholar The present study longer PWD values ± 12 than previous S.A. P-wave of values from the Heart PubMed Scopus Google Scholar, of P-wave dispersion values in the of clinical 17: PubMed Scopus Google Scholar but this may be to a larger of subjects >75 years in the present study in the Heart the included age to 45 years of of P-wave dispersion values in the of clinical 17: PubMed Scopus Google Scholar have the age of PA-TDI A. F. M. of total atrial conduction time measurement by tissue Doppler echocardiography according to age and in 2016; Full Text Full Text PDF PubMed Scopus Google Scholar, B. Vos C.B. Tieleman R.G. R. Cheriex E.C. M.H. Crijns H.J. and echocardiographic of conduction 2011; PubMed Scopus Google Scholar et A. F. M. of total atrial conduction time measurement by tissue Doppler echocardiography according to age and in 2016; Full Text Full Text PDF PubMed Scopus Google Scholar demonstrated in subjects between and 40 years that the PA-TDI duration increased with age (β = p = et B. Vos C.B. Tieleman R.G. R. Cheriex E.C. M.H. Crijns H.J. and echocardiographic of conduction 2011; PubMed Scopus Google Scholar evaluated the of PA-TDI in patients and a mean PA-TDI duration of ± ms, age was independently associated with PA-TDI on analysis increase in age was associated with 5 increase in that study included a of patients history of atrial heart and valvular heart and the PA-TDI values reflect more than the effect of the association between aging and changes in LA reservoir strain has been demonstrated in previous J.P. Yang Y. Guo R. Wang D. Lee A.P. Wang X.Y. Lam Y.Y. Fang F. Yang X.S. Yu C.M. Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: normal values and effects of aging in a large group of normal subjects.Int J Cardiol. 2013; 168: 3473-3479Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 5Evin M. Redheuil A. Soulat G. Perdrix L. Ashrafpoor G. Giron A. Lamy J. Defrance C. Roux C. Hatem S.N. Diebold B. Mousseaux E. Kachenoura N. Left atrial aging: a cardiac magnetic resonance feature-tracking study.Am J Physiol Heart Circ Physiol. 2016; 310: H542-H549Crossref PubMed Scopus (33) Google Scholar, A.C. T. Thomas L. Atrial strain rate is a of in atrial phasic function in 2011; 97: PubMed Scopus Google Scholar, K. M. H. T. Y. R.M. of aging on left atrial function by Am Soc Echocardiogr. 22: Full Text Full Text PDF PubMed Scopus Google Scholar In 188 subjects to of cardiovascular disease or cardiovascular risk Boyd et A.C. T. Thomas L. Atrial strain rate is a of in atrial phasic function in 2011; 97: PubMed Scopus Google Scholar that strain of the LA reservoir was independently associated with the in LA reservoir strain was from the LA dilation was from the suggesting that LA strain may be more of structural LA changes than echocardiographic In the present were changes in LA volume and LV a of diastolic with The association between age and LA reservoir strain was modulated by LA suggesting that diastolic to dilation of the and the of age on LA reservoir strain is In the present study demonstrated that LA reservoir strain is independently associated with In and has been demonstrated that the increase of tissue is associated with increased LA and reduced LA G. remodeling in Cardiovasc Imaging. 2013; PubMed Scopus Google Scholar In patients with et D. A. M. of atrial in Cardiol. 2015; PubMed Google Scholar that LA reservoir strain was more reduced in patients with ± ± p be The present study was in and not subjects because a cardiovascular risk or used cardiovascular that may LA for were between age and properties of the LA. The clinical of and are to of risk may the age-related changes in the properties of the LA. a of the study have for evaluation of changes in LA properties according to changes in In cardiac magnetic resonance was not performed to the of LA fibrosis and with the LA LA strain were performed with and the values obtained with this software may not be to The of Cardiology of the Leiden University Medical Center from and from
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Abou et al. (2017) conducted an observational in Without structural heart disease (n=386). Aging was evaluated on P-wave dispersion, PA-TDI duration, and LA reservoir strain (PWD β=0.161, PA-TDI β=0.476, LA strain β=-0.259, p=<0.001).
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