Changes in Left Atrial Size in Patients with Lone Atrial Fibrillation

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1 Clin. Cardiol. 14, (1991) Changes in Left Atrial Size in Patients with Lone Atrial Fibrillation GUILLERMO SOSA SUAREZ, M.D., SIEVEN LAMPERT, M.D., F.A.C.C., SHMUEL RAVID, M.D., BERNARD LOWN, M.D., F.A.C.C. Lown Cardiovascular Center, Department of Nutrition, Harvard School of Public Health, and the Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts, USA Summary: A retrospective analysis was performed on 23 subjects with lone atrial fibrillation who were followed for an average of 6.2 years ( years). In all patients, underlying organic heart disease was excluded based on history. physical exam, electrocardiogram, echocardiogram, and Doppler ultrasound interrogation. All patients had at least two echocardiographic studies during the period of observation. Atrial fibrillation was chronic in 1 I subjects and paroxysmal in 12. All echocardiographic measurements were obtained by averaging the measurements of two blinded investigators. Left atrial size increased an average of 5.6 mm which translates into a 14.7% increase over the baseline measurement. This increase in size was not associated with a change in left ventricular mass or fractional shortening as determined by echocardiography. Subjects with chronic atrial fibrillation had a larger percent increase lhan subjects with paroxysmal atrial fibrillation (18.9 vs. 10.8%)). although this relative change in size failed to reach statistical significance. The only variable which significantly contributed to the change in left atrial size was the duration of follow-up. We conclude that atrial fibrillation occurring in patients with lone atrial fibrillation may cause a slow and progressive increase in left atrial size independen@ of changes in left ventricular size or function. Key words: atrial fibrillation, left atrium, echocardiography, ~OIIOW-UP study Introduction Atrial fibrillation is frequently associated with left atrial enlargement. It remains unresolved whether the ar- rhythmia by itself causes left atrial dilatation or whether chamber enlargement is a consequence of the very factors which frequently result in the fibrillation, namely increased left atrial pressure due either to structural heart disease or to left ventricular dysfunction. When mitral stenosis and atrial fibrillation coexist, the relative contribution of each to the left atrial enlargement is difficult to assess. Some investigators have postulated that the degree of obstruction was the critical determinant of left atrial enlargement.'-3 Other researchers disagreed, suggesting that the enlarged left atrium is a direct consequence of the atrial A recent prospective study utilizing regression analysis suggested that the severity of mitral stenosis accounted for most of the change in left atrial size, although atrial fibrillation made a small but independent contribution.' In the absence of valvular heart disease, atrial fibrillation is often associated with left atrial enlargement. In a heterogenous cohort free of valvular heart disease,x left atrial size was related to the duration of the arrhythmia and increased during a 6-month follow-up period. An ideal cohort for determining whether atrial fibrillation causes an increase in left atrial size exists among patients with lone atrial fibrillation. Evans and Swann' did not find left atrial enlargement in 20 patients with this disorder nor in four patients followed for 10 years. A recent prospective study on 15 patients followed for 20 months suggested that the increase in left atrial size was a consequence of atrial fibrillation.'" The present study was designed to determine the influence of atrial fibrillation on changes in echocardiographically determined left atrial size in a population free of structural heart disease and followed for one year or longer. To define this effect better, a comparison was made between the paroxysmal and sustained type of atrial fibrillation. Address for reprints: Steven Larnpert, M.D. Lecturer in Cardiology Harvard School of Public Health 2 I Longwood Avenue Brookline, MA 02146, USA Receivcd: February Accepted with revision: April 23, 1991 Methods Patient Selection We reviewed the records in 436 patients with atrial fibrillation examined by our group between 1982 and We selected 23 patients who were free of structural heart disease based on a normal history, physical examination, echocardiogram and Doppler ultrasound interrogation. At

2 G. S. Suarez et al.: Left atrial size in lone atrial fibrillation 653 least two echocardiographic examinations were required for inclusion in this study. Exclusion Criteria Patients were excluded for the following reasons: a history of rheumatic, ischemic, or hypertensive heart disease, valvular heart disease diagnosed by either physical exam or Doppler echocardiography, congestive heart failure, pre-excitation syndromes, hyperthyroidism, excessive alcohol intake, or cardiomyopathy. Patient Categories In all patients the presence of atrial fibrillation was documented electrocardiographically. Atrial fibrillation was chronic in 11 patients and paroxysmal in 12 patients. Paroxysmal atrial fibrillation was defined as at least two documented episodes of atrial fibrillation with an intervening period of normal sinus rhythm. In this group the echocardiogram was obtained in normal sinus rhythm. The average age was 63.0k9.1 years and was not different in the two groups. There were 18 men and 5 women equally distributed in the two groups. Follow-Up Patients were followed for an average of 6.2 years ( I. I years), those with chronic atrial fibrillation were followed for 7.0 years compared with 5.4 years in the paroxysmal group (p =). Echocardiographic Studies Equipment Echocardiographic studies performed prior to 1982 utilized an IREX M-mode ultrasound system. Only M-mode studies were performed prior to 1982; thereafter all studies includd two-dimensional guided M-mode echocardiogram. After 1985, all studies were performed on a Hewlett Packard ultrasonoscope equipped with a 2.5 MHz transducer and M-mode, two-dimensional echocardiography, and both pulse wave and continuous wave Doppler echocardiographic capabilities. Number of Echocardiographic Studies All patients underwent an average of 3.0 ( ) echocardiographic studies during the follow-up period. All patients underwent at least one recent Doppler echocardiographic study to further exclude the presence of valvular heam disease. Echocardiographic Measurements M-mode tracings were of good quality and allowed accurate measurement of cardiac chambers. The following measurements, adhering to the criteria of the American Society of Echocardiography,! were made in all subjects: left atrial anterior-posterior dimension, including the posterior aortic wall at end ventricular systole; left ventricular end-diastolic dimension; left ventricular end-systolic dimension; septa1 and posterior wall thickness. Left atrial size was adjusted for body surface area, calculated at the time of each echocardiographic study. The fractional shortening (FS) was calculated for each echocardiographic study according to the following formula: FS (%) = [(LVD-LVS)/LVD] x 100 Left ventricular mass was calculated for each echocardiographic study according to the anatomically corrected regression equation of Devereaux:12 Left ventricular mass (g)= 1.04 [(LVD+IVS+LVPW) 3-(LVD) where LVD= left ventricular diastolic diameter, LVS =left ventricular systolic diameter, IVS =interventricular septum thickness, and LVPW =posterior wall thickness. Left ventricular mass was then adjusted for height.i3 All echocardiographic studies were interpreted by two readers (SL; SR), who were blinded with regard to the diagnosis, temporal sequence, and subject. Pearson correlation coefficients were calculated for each pair of measurements. The correlation coefficient for left atrial size was.96. The correlation coefficients for left ventricular diastolic diameter, systolic diameter, interventricular septum, and posterior wall were 0.83,0.75,0.50, and 0.45, respectively. The two observers measurements were then averaged. After confirming the reliability of the two readers, the initial and final echocardiograms were selected for all subsequent analysis. Statistical Analysis Data were expressed as the mean and standard deviation. The unpaired Student s t-test was used to compare between group measurements. Within subjects changes in echocardiographic measurements were analyzed with a paired Student s t-test. Multiple regression analysis was performed to evaluate the relative contribution of age, duration of follow-up, baseline echocardiographic measurements, and type of atrial fibrillation on the change in left atrial size. Statistical significance was defined as p< In the entire cohort, the left atrial size increased an average of 5.6f6 mm during the follow-up period (p<.ool). The median change was 6 mm and the average percent increase in size was 14.7%. When corrected for body surface area, the increase in left atrial size was 2.9f3 mm/m2

3 654 Clin. Cardiol. Vol. 14, August 1991 (p<0.001). There was no significant change in left ventricular end-diastolic or end-systolic dimension; similarly, fractional shortening was stable during the observation period. The left ventricular mass increased 35.9f53 g during the observation period (p =.02); the normalized left ventricular mass increased by 21.7f3 1 g/m (p=.02). The percentage increases for these values were % and 22.0%, respectively. Baseline and final echocardiographic measurements in the chronic atrial fibrillation and paroxysmal fibrillation groups are presented in Tables I and 11. At the start of the observation period, measures of left ventricular size, function, and mass were similar in the two groups. Left atrial size was significantly larger in the chronic atrial fibrillation group compared with the paroxysmal atrial fibrillation group both at the inception (p=.o3) and conclusion of the study (p<.004). When corrected for body surface area, the baseline left atrial size was not significantly different, but the final corrected left atrial size was significantly larger in the group with chronic atrial fibrillation (p<.05). There was an 18.9% increase in the left atrial size in the chronic atrial fibrillation group, compared with 10.8% in patients with paroxysmal atrial fibrillation (p=). Within each group, the increase in left atrial size was significant whether evaluated as an absolute change or a percentage in- crease over the baseline. These differences were maintained when left atrial size was corrected for body surface area. Left ventricular mass increased by 17.7f50 g in the chronic atrial fibrillation group, and by 60.1 f 50 g in the paroxysmal atrial fibrillation group (p=). In distinction, all measures of left ventricular function were unchanged in both groups during the follow-up period. Multiple regression analysis was performed to identify variables which significantly contributed to the change in left atrial size. Only the total duration of follow-up (p=.01) was associated with the increase in atrial size. Simple linear regression analysis demonstrated that the left atrium increased approximately 1 mm per year of follow-up (Fig. 1). Baseline and final measures of age, heart rate, fractional shortening, and LV mass were unrelated to the absolute increase in left atrial size. Similarly, the type of fibrillator, chronic or paroxysmal, could not explain the increase in left atrial size. Discussion This retrospective study presents the long-term follow-up of patients with true lone atrial fibrillation that have been assessed both clinically and echocardiograph- TABLE I Individual echocardiographic measurements in patients with lone atrial fibrillation ~ ~ Duration Age at end LA start LA end ALA FSH start FSH end Case (month) (yrs) (mm) (mm) (mm) (%I (%) AFS H Chronic atrial fibrillation X I Average 84.1 Paroxysmal atrial fibrillation I1 I IX Averare 64.8 Ahhreviutions: LA= left atrial; FSH=fractional shortening O I

4 ~ G. S. Suarez ef al.: Left atrial size in lone atrial fibrillation 655 TABLE I1 Baseline and final echocardiogradhic measurement in Datients with lone atrial fibrillation Number Baseline Measurement Left atrial size (mm) Left atrial size index" (mm/m?) Left ventricle End-diastole (cm) End-systole (cm) Fractional shortening (%) Left ventricular mass (g) Left ventricular mass index (dm) Heart rate (beats/min) Final Measurements Left atrial size (mm) Left atrial size index" ( mm/m2) Left ventricle End-diastole (cm) End-systole (cm) Fractional shortening (%) Left ventricular mass (g) Left ventricular mass index (dm).-. Heart rate (beats/min) "Corrected for body surface area. Chronic f f f f f f f f f f f f f I f f f 28 Paroxysmal f f f f f f f f f f f f f zk 56 1 f f 9 p Value ~ ically for an average of 6.2 years ( yrs). The role of the arrhythmia on changes in left atrial dimension is best addressed in a population with lone atrial fibrillation because confounding hemodynamic abnormalities are excluded. We studied a population of men and women who were free of cardiac disease except for atrial fibrillation. The arrhythmia was the only cardiac problem for which they sought medical care. The length of follow-up permitted screening out all those patients who demonstrated cardiac conditions that might have contributed to atrial enlargement. -5t * t Duration of follow-up (months) Frci. I Change in left atrial size as a function of time. The regression equation was: change in LA size= (months of follow-up). * Our findings indicate that left atrial size increases in patients with atrial fibrillation even in the presence of structurally normal hearts. The degree of dilatation relates primarily to the duration of the arrhythmia. The change in atrial size was more noteworthy when the fibrillation was sustained. Patients with chronic atrial fibrillation tended to have larger left atrium. Over time, this group exhibited a larger increase in left atrial diameter, which failed to achieve statistical significance due to the small sample size. We did not observe an association between left atrial size and left ventricular systolic function which remained unaltered for the duration of this study. Similarly, left ventricular mass was not associated with left atrial size, nor did the increase in left ventricular mass account for the increase in left atrial size. This study has some potential limitations. Left ventricular diastolic function was not directly assessed. However, none of the patients had left ventricular hypertrophy or conditions associated with decreased ventricular compliance. Systolic function was not evaluated by an independent method, such as radionuclide ventriculography. Impaired systolic function, however, is very unlikely in the absence of clinical or echocardiographic evidence of regional wall motion abnormalities or valvular lesions. Whether atrial fibrillation is the cause or the consequence of atrial enlargement has been a source of controversy for many years. Evans and Swann9 in their pioneer description of "lone" atrial fibrillation more than three decades ago were not able to document the development

5 6.56 Clin. Cardiol. Vol. 14, August 1991 of left atrial enlargement in four patients followed for over I0 years. Other researchers have identified atrial fibrillation as an independent contributor to atrial enlargement in patients with mitral stenosis.j- Petersen rt UI.,~ studying a mixed population of cardiac patients with atrial fibrillation over a 6-month period, found a significant increase in lefi atrial size. However, they presented no data correlating this with changes in left ventricular dimensions or function. Sanfilippo et ui. recently reported an increase in left atrial size in the absence of significant mitral regurgitation, mitral valve pathology or left ventricular disease in 15 patients with atrial fibrillation followed for 20 rnonths. j Our results are consonant with their findings and, by contrasting chronic from paroxysmal atrial fibrillation, we extend the observation that atrial fibrillation may independently cause an increase in left atrial size. In addition, our study observed the changes in left atrial size over a 6-year time period. Wc conclude that chronic atrial fibrillation occurring in patients with structurally normal hearts ( lone atrial fibrillation ), may cause a slow and progressive increase in left atrial size. The enlargement relates to the total duration of the arrhythmia and is independent of changes in LV size or function. The rate of change in left atrial size observed in this sluily needs to be verified by a long-term prospective study. References I. Gorlin R: Naiurnl history, medical therapy and indications for wrgery in mitral valve disease. In Mitrul Vuhv Disease: Di agnosis and Treatment (Eds. Ionescu MI, Cohn LH). Butterworth & Co., Ltd., Boston ( I 985) Selzer A, Cohn KE: Natural history of mitral stenosis: A review. Circwlution 45, (1972) Abildskov JA, Millar K, Burgess MJ: Atrial fibrillation. Am.I Curdiol (1971 ) Probst P, Goldschlager N, Selzer A: Left atrial size and atrial fibrillation in mitral stenosis. Factors influencing their relationship. Ciruulution (1973) Selzer A: Atrial fibrillation revisited. N En,?/.I Med (19x2) Davies MJ, Pommerance A: Pathology of atrial fibrillation in man. Br Heart J 34, (1972) Keren G, Etzion T, Sherez J, Zelcer AA, Megidish R. Miller 131, Laniado S: Atrial fihrillation and atrial enlargement in patients with mitral stenosis. Am Heart J 114, (1987) Petersen P, Kastrup J. Brinch K. Dogtfredsen J, Boysen G: Relationship between left atrial dimension and duration of atrial fibrillation. Am J Cardiol (1987) Evans W, Swam P: Lone auricular fibrillation. Br Heart./ (1954) Sanfilippo AJ, Abascal VM, Sheehan M, Dertel LB, Harrigan P, Hughes RA, Weyman AE: Atrial enlargement as a consequence of atrial fibrillation. A prospective echocardiographic Study. Ci~~rl~/i~n 83, (1990) Sahn DJ, DeMaria A, Kisslo J, Weyman A: Recommendations regarding quantitation in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circwlation 58, (1978) Devereux RB, Reichek N: Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circrtlation 55, (1977) Levy D, Garrison RJ, Savage DD, Kannel WB. Castelli WP: Left ventricular mass and incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study. Ann Intern Med 110, (1989)

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