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Assessment of left atrial appendage function and its relationship to pulmonary venous flow pattern by transesophageal echocardiography
International Journal of Cardiology 78 (2001) 121–126 www.elsevier.com / locate / ijcard
Assessment of left atrial appendage function and its relationship to pulmonary venous flow pattern by transesophageal echocardiography q ¨ *, Dursun Atilgan, Vakur Akkaya, Hasan Kudat, Seref Demirel, Mustafa Ozcan, ¨ Tufan Tukek Ferruh Korkut Cardiovascular Research Center, Istanbul Faculty of Medicine, Istanbul, Turkey Received 20 July 2000; received in revised form 28 November 2000; accepted 6 December 2000
Abstract We evaluated left atrial appendage function and its relationship to pulmonary venous flow in 53 patients divided into four groups. Group 1 consisted of 10 normal subjects. Group 2 included 15 patients with significant pure mitral stenosis in sinus rhythm. In group 3, there were 13 patients with pure significant mitral stenosis and atrial fibrillation. Group 4 consisted of 15 patients with normal mitral valve and atrial fibrilltion. We found significant decrease in left atrial appendage ejection fraction and maximum emptying flow velocity, velocity time integral of systolic pulmonary venous flow in Groups 2, 3 and 4 in comparison with normal subjects. Systolic pulmonary venous flow velocity was significantly decreased in Groups 3 and 4. There was significant correlation between left atrial appendage ejection fraction and peak emptying flow velocity (r50.62, P,0,001). Systolic peak pulmonary venous flow velocity was significantly correlated with left atrial appendage ejection fraction and maximum emptying flow velocity (r50.67, P50,01; r50.58, P,0,001, respectively). There was also significant correlation between systolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.66, P50.001). When normals were excluded from analysis, all the correlations were still significant. We concluded that left atrial appendage is a contractile structure, and that systolic pulmonary venous flow velocity is influenced by left atrial appendage dysfunction. Therefore left atrial appendage function needs to be considered when interpreting Doppler transmitral and systolic pulmonary venous flow patterns. 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Left atrial appendage function; Pulmonary venous flow
1. Introduction So far, much attention has been given to the left atrial appendage because of its high susceptibility to the thrombus formation due to its blind pouch shape
q
This was accepted for poster presentation at Congress of the European Society of Cardiology, Amsterdam, 2000. ¨ ¨ *Corresponding author. Seyit Omer Mahallesi, Seyit Omer cami sok., Armutcu appartment number 9, D:10, Sehremini, Istanbul, Turkey. Fax: 190-212-534-0934. ¨ E-mail address: [email protected] (T. Tukek).
[1,2]. Recent experimental studies also suggested that ligation or removal of left atrial appendage disturbs the physiologic compensatory mechanism for left atrial reservoir function, and that the left atrial appendage plays an important role in left atrium compliance as assessed from pulmonary venous flows [3–5]. However, there is little information regarding the relation of left atrial appendage function to pulmonary venous flows pattern in human. In this study, we characterized the pathological changes of left atrial appendage and investigated the correlation between left atrial appendage function and pulmonary venous flows pattern.
0167-5273 / 01 / $ – see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00474-5
122
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
2. Methods
2.1. Subjects The study population included 53 patients divided into four groups. Group 1 consisted of 10 healthy subjects (male / female (M / F):7 / 3, aged 41616 years) with normal physical examination, electrocardiography, stress test and echocardiography. Group 2 included 15 patients (M / F:7 / 8, aged 3769 years) with significant pure mitral stenosis in sinus rhythm. In group 3, there were 13 patients (M / F:5 / 8, aged 49616 years) with pure significant mitral stenosis and atrial fibrillation. Group 4 consisted of 15 patients (M / F:11 / 4, aged 63610 years) with normal mitral valve and atrial fibrillation. Mitral valve area larger than 1.5 cm 2 , significant mitral regurgitation, and left ventricular ejection fraction less than 0.50 were the exclusion criteria from the study. Patients with anular mitral calcification or valvular lesion other than mitral stenosis were also excluded from the study.
2.2. Echocardiography Transthoracic studies were performed using a 2.5 MHz transducer with a Hewlett-Packard cardiac imaging system (Hewlett-Packard Sonos 1000, Andover, MA). Left ventricular and left atrial dimensions, left ventricular ejection fraction were measured from the M-mode echocardiogram following the recommendations of the American Society of Echocardiography [6]. Mitral valve area was calculated by the pressure-half time method [7]. For transesophageal echocardiography, a 5 MHz monoplane transducer and the same apparatus were used. The echocardiographic probe was inserted into the esophagus under local pharyngeal anesthesia in the left lateral decubitus position. Patients fasted for at least 6 h. A one-lead electrocardiogram was displayed on the monitor. The investigations were carried out without any complication. In all subjects, the left atrial appendage was visualized at the level of aortic valve in transverse imaging plane as a triangular structure anteromedial to the left superior pulmonary vein. Maximal and minimal left atrial appendage areas were determined by computer-assisted planimetry
from the tip of the appendage to its junction with the main left atrial body. In sinus rhythm, maximal and minimal left atrial appendage areas were measured at the time immediately before the P-wave and just after the QRS complex, on the electrocardiogram. In atrial fibrillation, maximal and minimal left atrial appendage areas were obtained within a cardiac cycle, independent of the electrocardiogram [1]. Left atrial appendage ejection fraction was calculated as 1003(left atrial appendage maximal area2left atrial appendage minimal area) / left atrial appendage maximal area [1]. The maximal left atrial appendage emptying flow velocity was measured by placing the Doppler sample volume 1 cm inside the left atrial appendage outlet. Peak systolic pulmonary venous flow velocity and velocity time integral, peak diastolic pulmonary venous flow and velocity time integral were measured with the Doppler sample volume placed 1–2 cm into the left superior pulmonary vein. Mitral regurgitation was assessed by visual evaluation of color flow Doppler mapping as mild, moderate, moderate-severe, and severe [8]. All measurements were calculated as the average of five consecutive cardiac cycles in atrial fibrillation and three consecutive cycles in sinus rhythm. Declaration of Helsinki’s guidelines on biomedical research in human subjects were followed [9].
2.3. Statistical analysis Results are expressed as the mean6S.D. For statistical difference between the four groups oneway analysis of variance (ANOVA) was carried out. Post-hoc analysis for significance after ANOVA test, Tukey’s HSD was used. Categoric variables were assessed by the chi-square test. Correlation of numerical variables were done with Spearman’s correlation test. A P-value,0.05 was considered significant. All morphologic and Doppler echocardiographic measurements showed ,5% interobserver variability.
3. Results The characteristics of left atrial appendage and pulmonary venous flow of each group of patients are
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
123
Table 1 Characteristics of LAA and PVF of each group a Groups
LA (mm)
LAAvmx (cm / s)
LAA-EF (%)
PVFs (cm / s)
PVFs-VTI (cm)
PVFd (cm / s)
PVFd-VTI (cm)
Normals MS1SR MS1AF AF
2965 4765 b 55610 b 4466 b
61623 29618 b 966 b,c 20610 b
51613 22613 b 12610 b 21612 b
59616 44616 28617 b,c 3067 b
11.264.2 5.962.4 b 3.361.2 b,c 3.861.2 b
48610 46613 40615 45617
6.762.2 6.062.3 5.262.7 6.162.9
a
Values are expressed as the mean6S.D. LAA, left atrial appendage; PVF, pulmonary venous flow; MS, mitral stenosis; SR, sinus rhythm; AF, atrial fibrillation; LAAvmx, maximum left atrial appendage emptying flow velocity; LA, left atrium; EF, ejection fraction; PVFs, peak systolic pulmonary venous flow velocity; PVFd, peak diastolic pulmonary venous flow velocity; and VTI, velocity time integral. b P,0.05 vs. Group 1. c P,0.05 vs. Group 2.
shown in Table 1. In Groups 2, 3 and 4, peak left atrial appendage emptying flow velocity, left atrial appendage ejection fraction, systolic pulmonary venous flows velocity time integral were significantly lower, and left atrium was larger compared to Group 1. In Groups 3 and 4, peak systolic pulmonary venous flow velocity was slower than in that of Group 1. Significant difference was noted in peak left atrial appendage emptying flow velocity, peak systolic pulmonary venous flow velocity and velocity time integral between Groups 2 and 3. In Group 2, patients tended to have lower peak systolic pulmonary venous
flow velocity than that of normals but the difference didn’t reach statistical significance. There was a significant linear correlation between peak left atrial appendage emptying flow velocity and left atrial appendage ejection fraction (r50.62, P, 0.001, Fig. 1). A significant correlation was also noted between peak systolic pulmonary venous flow velocity and left atrial appendage function (Left atrial appendage ejection fraction: r50.67, P,0.001, Fig. 2; peak left atrial appendage emptying flow velocity: r50.58, P,0.001, Fig. 3). When normals were excluded from analysis, all the correlations were still
Fig. 1. Correlation between LAA ejection fraction (LAA EF) and maximum LAA emptying flow velocity (LAAvmx).
124
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
Fig. 2. Correlation between LAA ejection fraction (LAA EF) and peak systolic PVF velocity (PVFs).
Fig. 3. Correlation between maximum LAA emptying flow velocity (LAAvmx) and peak systolic PVF velocity (PVFs).
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
significant; r50.50, P50,001; r50.46, P50.003; r5 0.44, P50.005, respectively. There was also significant correlation between systolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.66, P50.001). When normals were excluded from analysis, the correlation was still statistically significant (r50.48, P50.002). There was no significant correlation between diastolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.12, P50.44; r50.11, P50.44 when normals excluded).
4. Discussion Left atrial appendage dysfunction has been described in patients with atrial fibrillation, with or without mitral stenosis but the left atrial appendage function is not well known in patients with mitral stenosis in sinus rhythm [1,2]. Jue et al. [10] first studied the possible relation of peak left atrial appendage emptying flow velocity to pulmonary venous flows, and concluded that left atrial appendage flow was independent of pulmonary venous flows. However, they included patients with severe mitral regurgitation which can affect both peak left atrial appendage emptying flow velocity and pulmonary venous flows because of the turbulent regurgitant jet. In recent experimental studies, it has been shown that removal of left atrial appendage decreases left atrial compliance and increases left atrial pressure at any given volume, and that left atrial appendage plays important role in left atrium reservoir function [3–5]. After removal of left atrial appendage in openchest dogs, Hoit et al. [4] demonstrated increases in the ratio of systolic pulmonary venous flow to diastolic pulmonary venous flow as an index of the relative reservoir to conduit function of the left atrium. In contrast, Tabata et al. [5] showed that systolic pulmonary venous flow significantly decreased and diastolic pulmonary venous flow significantly increased after left atrial appendage clamping in 15 patients during cardiac surgery. Recently, Ito et al. [11] studied left atrial appendage function in 23 patients with dilated cardiomyopathy and 25 patients with hypertrophic cardiomyopathy. In their study, patients with left atrial appendage dysfunction
125
tended to have a lower systolic pulmonary venous flow velocity and a higher diastolic pulmonary venous flow velocity than those with normal left atrial appendage function, but the differences didn’t reach statistical significance. The origin of the systolic pulmonary venous flow is less clear, and there is considerable disagreement in the literature. Some authors suggest that the systolic pulmonary venous flow is caused by pressure changes in the left atrium having suction effect [12– 14]. Several other experimental studies in dog models conclude that systolic pulmonary venous flow is generated predominantly by transmission of the right ventricular pressure pulse through the pulmonary vascular bed [15–18]. Smiseth et al. [19] have suggested that systolic pulmonary venous flow appears to be determined by right as well as left-sided cardiac effects. Nakatani et al. [20] have reported that a combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of left atrial function. In light of these findings, we evaluated pathological changes of the left atrial appendage in different groups of patients, who were expected to have left atrial appendage dysfunction, and we also investigated correlation between the left atrial appendage function and pulmonary venous flows pattern. The significant correlation we found between left atrial appendage ejection fraction and peak left atrial appendage emptying flow velocity indicates the left atrial appendage contractile function. The significant left atrial appendage dysfunction we also noted in Group 2 patients, as shown by the reduced peak left atrial appendage emptying flow velocity and left atrial appendage ejection fraction, suggests that the left atrial appendage function is not only influenced by atrial fibrillation but also by mitral stenosis itself. The significant correlation we found between peak left atrial appendage emptying flow velocity and peak systolic pulmonary venous flow indicates the relation of left atrial appendage emptying flow to the systolic phase of pulmonary venous flow. In our study, none of our patients had significant mitral regurgitation. On the other hand, the significant correlation between left atrial appendage ejection fraction and peak systolic pulmonary venous flow velocity in our study confirms that pulmonary venous flows pattern is influenced by left atrial appendage function. The
126
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
significant decrease in left atrial appendage ejection fraction, peak left atrial appendage emptying flow velocity together with systolic pulmonary venous flow velocity and velocity time integral in Groups 2, 3 and 4 in comparison with normal subjects also supports this concept. In their study, Paraskevaidis et al. [21] did not demonstrate relationship between atrial fibrillation and both peak systolic and diastolic pulmonary venous flow velocities but they did not investigate the effect of left atrial appendage function on pulmonary venous flows pattern. We also did not find significant decresase in peak diastolic pulmonary venous flow velocity in atrial fibrillation but there was significant decrease in both left atrial appendage function and peak systolic pulmonary venous flow velocity in Groups 3 and 4 patients. Therefore we thought that atrial fibrillation does not play significant role in the pathogenesis of pulmonary venous flows pattern but left atrial appendage function has important effect on systolic pulmonary venous flow. In conclusion, our results suggest that left atrial appendage is a contractile structure, and that left atrial appendage dysfunction has a detrimental effect on systolic phase of pulmonary venous flows which is thought to reflect left atrial compliance. Therefore left atrial appendage function needs to be taken into account when interpreting Doppler transmitral and systolic pulmonary venous flow patterns but further studies should be done to determine the potential contribution from reflected waves.
Acknowledgements ¨ for her excelWe gratefully thank Zahide Ac¸ikgoz lent technical aid in data collection.
References [1] Pollick C, Taylor D. Assessment of left atrial appendage function by transesophageal echocardiography: implications for the development of thrombus. Circulation 1991;84:223–31. [2] Michalis LK, Thomas MR, Smyth DW, Why HJF, Monaghan MJ, Jewitt DE. Left atrial spontaneous echo contrast assessed by TEE in patients with either native mitral valve disease or mitral valve replacement. J Am Soc Echocardiogr 1993;6:299–307.
[3] Davis CA, Rembert JC, Greenfield JC. Compliance of the left atrium with and without left atrium appendage. Am J Physiol 1990;259:H1006–8. [4] Hoit BD, Shao Y, Tsai LM, Patel R, Gabel M, Walsh RA. Altered left atrial compliance after atrial appendectomy: influence on left atrial and ventricular filling. Circ Res 1993;72:167–75. [5] Tabata T, Oki T, Yamada H et al. Role of left atrial appendage in left atrial reservoir function as evaluated by left atrial appendage clamping during cardiac surgery. Am J Cardiol 1998;81:327–32. [6] Sahn DJ, de Maria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–83. [7] Hatle L, Angelsen B, Tromsdal A. Non-invasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation 1979;60:1096–104. [8] Mowsowitz C, Mowsowitz HD, Jacobs LE, Meyerowitz CB, Podolsky LA, Kotler MN. Significant mitral regurgitation is protective against left atrial spontaneous echo contrast and thrombus assessed by transesophageal echocardiography. J Am Soc Echocardiogr 1993;6:107–14. [9] Declaration of Helsinki. Recommendation guiding physicians in biomedical research involving human subjects. 41st World Medical Assembly, Hong-Kong, September, 1989. [10] Jue J, Winslow T, Fazio G, Redberg RF, Foster E, Schiller NB. Pulsed Doppler characterization of left atrial appendage flow. J Am Soc Echocardiogr 1993;6:237–44. [11] Ito T, Suwa M, Hirota Y, Otake Y, Moriguchi A, Kawamura K. Influence of left atrial function on Doppler transmitral and pulmonary venous flow patterns in dilated and hypertrophic cardiomyopathy: evaluation of left atrial appendage function by transesophageal echocardiography. Am Heart J 1996;131:122–30. [12] Morgan BC, Abel FL, Mullins GL, Guntherorth WG. Flow patterns in cavae, pulmonary artery, pulmonary vein and aorta in intact dogs. Am J Physiol 1966;210:903–9. [13] Rajagopalan B, Friend JA, Stallard T, Lee G de J. Blood flow in pulmonary veins: I Studies in dog and man. Cardivasc Res 1979;13:667–76. [14] Rajagopalan B, Friend JA, Stallard T, Lee G de J. The influence of events transmitted from the right and left sides of the heart. Cardiovasc Res 1979;13:677–83. [15] Guntheroth WG, Gould R, Butler J, Kinnen E. Pulsatile flow in pulmonary artery, capillary and vein in the dog. Cardiovasc Res 1974;8:330–7. [16] Morkin E, Collins JA, Goldman HS, Fishman AP. Pattern of blood flow in the pulmonary veins of dogs. J Appl Physiol 1965;20:1118– 28. [17] Pinkerson AL. Pulse-wave propagation through the pulmonary vascular bed of dogs. Am J Physiol 1967;21:450–4. [18] Szidon JP, Ingram RH, Fishman AP. Origins of the pulmonary venous flow pulse. Am J Physiol 1968;214:10–4. [19] Smiseth OA, Thompson CR, Lohavanichbutr K et al. The pulmonary venous systolic flow pulse-its origin and relationship to left atrial pressure. J Am Coll Cardiol 1999;34:802–9. [20] Nakatani S, Garcia MJ, Firstenberg MS et al. Noninvasive assessment of left atrial maximum dP/ dt by a combination of transmitral and pulmonary venous flow. J Am Coll Cardiol 1999;34:795–801. [21] Paraskevaidis IA, Theodorakis GN, Katritsis DG, Tsiapras DP, Livanis EG, Kremastinos DT. Pulmonary vein flow analysis by transesophageal echocardiography in patients with chronic atrial fibrillation. Eur Heart J 1999;20:375–85.
Assessment of left atrial appendage function and its relationship to pulmonary venous flow pattern by transesophageal echocardiography q ¨ *, Dursun Atilgan, Vakur Akkaya, Hasan Kudat, Seref Demirel, Mustafa Ozcan, ¨ Tufan Tukek Ferruh Korkut Cardiovascular Research Center, Istanbul Faculty of Medicine, Istanbul, Turkey Received 20 July 2000; received in revised form 28 November 2000; accepted 6 December 2000
Abstract We evaluated left atrial appendage function and its relationship to pulmonary venous flow in 53 patients divided into four groups. Group 1 consisted of 10 normal subjects. Group 2 included 15 patients with significant pure mitral stenosis in sinus rhythm. In group 3, there were 13 patients with pure significant mitral stenosis and atrial fibrillation. Group 4 consisted of 15 patients with normal mitral valve and atrial fibrilltion. We found significant decrease in left atrial appendage ejection fraction and maximum emptying flow velocity, velocity time integral of systolic pulmonary venous flow in Groups 2, 3 and 4 in comparison with normal subjects. Systolic pulmonary venous flow velocity was significantly decreased in Groups 3 and 4. There was significant correlation between left atrial appendage ejection fraction and peak emptying flow velocity (r50.62, P,0,001). Systolic peak pulmonary venous flow velocity was significantly correlated with left atrial appendage ejection fraction and maximum emptying flow velocity (r50.67, P50,01; r50.58, P,0,001, respectively). There was also significant correlation between systolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.66, P50.001). When normals were excluded from analysis, all the correlations were still significant. We concluded that left atrial appendage is a contractile structure, and that systolic pulmonary venous flow velocity is influenced by left atrial appendage dysfunction. Therefore left atrial appendage function needs to be considered when interpreting Doppler transmitral and systolic pulmonary venous flow patterns. 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Left atrial appendage function; Pulmonary venous flow
1. Introduction So far, much attention has been given to the left atrial appendage because of its high susceptibility to the thrombus formation due to its blind pouch shape
q
This was accepted for poster presentation at Congress of the European Society of Cardiology, Amsterdam, 2000. ¨ ¨ *Corresponding author. Seyit Omer Mahallesi, Seyit Omer cami sok., Armutcu appartment number 9, D:10, Sehremini, Istanbul, Turkey. Fax: 190-212-534-0934. ¨ E-mail address: [email protected] (T. Tukek).
[1,2]. Recent experimental studies also suggested that ligation or removal of left atrial appendage disturbs the physiologic compensatory mechanism for left atrial reservoir function, and that the left atrial appendage plays an important role in left atrium compliance as assessed from pulmonary venous flows [3–5]. However, there is little information regarding the relation of left atrial appendage function to pulmonary venous flows pattern in human. In this study, we characterized the pathological changes of left atrial appendage and investigated the correlation between left atrial appendage function and pulmonary venous flows pattern.
0167-5273 / 01 / $ – see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00474-5
122
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
2. Methods
2.1. Subjects The study population included 53 patients divided into four groups. Group 1 consisted of 10 healthy subjects (male / female (M / F):7 / 3, aged 41616 years) with normal physical examination, electrocardiography, stress test and echocardiography. Group 2 included 15 patients (M / F:7 / 8, aged 3769 years) with significant pure mitral stenosis in sinus rhythm. In group 3, there were 13 patients (M / F:5 / 8, aged 49616 years) with pure significant mitral stenosis and atrial fibrillation. Group 4 consisted of 15 patients (M / F:11 / 4, aged 63610 years) with normal mitral valve and atrial fibrillation. Mitral valve area larger than 1.5 cm 2 , significant mitral regurgitation, and left ventricular ejection fraction less than 0.50 were the exclusion criteria from the study. Patients with anular mitral calcification or valvular lesion other than mitral stenosis were also excluded from the study.
2.2. Echocardiography Transthoracic studies were performed using a 2.5 MHz transducer with a Hewlett-Packard cardiac imaging system (Hewlett-Packard Sonos 1000, Andover, MA). Left ventricular and left atrial dimensions, left ventricular ejection fraction were measured from the M-mode echocardiogram following the recommendations of the American Society of Echocardiography [6]. Mitral valve area was calculated by the pressure-half time method [7]. For transesophageal echocardiography, a 5 MHz monoplane transducer and the same apparatus were used. The echocardiographic probe was inserted into the esophagus under local pharyngeal anesthesia in the left lateral decubitus position. Patients fasted for at least 6 h. A one-lead electrocardiogram was displayed on the monitor. The investigations were carried out without any complication. In all subjects, the left atrial appendage was visualized at the level of aortic valve in transverse imaging plane as a triangular structure anteromedial to the left superior pulmonary vein. Maximal and minimal left atrial appendage areas were determined by computer-assisted planimetry
from the tip of the appendage to its junction with the main left atrial body. In sinus rhythm, maximal and minimal left atrial appendage areas were measured at the time immediately before the P-wave and just after the QRS complex, on the electrocardiogram. In atrial fibrillation, maximal and minimal left atrial appendage areas were obtained within a cardiac cycle, independent of the electrocardiogram [1]. Left atrial appendage ejection fraction was calculated as 1003(left atrial appendage maximal area2left atrial appendage minimal area) / left atrial appendage maximal area [1]. The maximal left atrial appendage emptying flow velocity was measured by placing the Doppler sample volume 1 cm inside the left atrial appendage outlet. Peak systolic pulmonary venous flow velocity and velocity time integral, peak diastolic pulmonary venous flow and velocity time integral were measured with the Doppler sample volume placed 1–2 cm into the left superior pulmonary vein. Mitral regurgitation was assessed by visual evaluation of color flow Doppler mapping as mild, moderate, moderate-severe, and severe [8]. All measurements were calculated as the average of five consecutive cardiac cycles in atrial fibrillation and three consecutive cycles in sinus rhythm. Declaration of Helsinki’s guidelines on biomedical research in human subjects were followed [9].
2.3. Statistical analysis Results are expressed as the mean6S.D. For statistical difference between the four groups oneway analysis of variance (ANOVA) was carried out. Post-hoc analysis for significance after ANOVA test, Tukey’s HSD was used. Categoric variables were assessed by the chi-square test. Correlation of numerical variables were done with Spearman’s correlation test. A P-value,0.05 was considered significant. All morphologic and Doppler echocardiographic measurements showed ,5% interobserver variability.
3. Results The characteristics of left atrial appendage and pulmonary venous flow of each group of patients are
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
123
Table 1 Characteristics of LAA and PVF of each group a Groups
LA (mm)
LAAvmx (cm / s)
LAA-EF (%)
PVFs (cm / s)
PVFs-VTI (cm)
PVFd (cm / s)
PVFd-VTI (cm)
Normals MS1SR MS1AF AF
2965 4765 b 55610 b 4466 b
61623 29618 b 966 b,c 20610 b
51613 22613 b 12610 b 21612 b
59616 44616 28617 b,c 3067 b
11.264.2 5.962.4 b 3.361.2 b,c 3.861.2 b
48610 46613 40615 45617
6.762.2 6.062.3 5.262.7 6.162.9
a
Values are expressed as the mean6S.D. LAA, left atrial appendage; PVF, pulmonary venous flow; MS, mitral stenosis; SR, sinus rhythm; AF, atrial fibrillation; LAAvmx, maximum left atrial appendage emptying flow velocity; LA, left atrium; EF, ejection fraction; PVFs, peak systolic pulmonary venous flow velocity; PVFd, peak diastolic pulmonary venous flow velocity; and VTI, velocity time integral. b P,0.05 vs. Group 1. c P,0.05 vs. Group 2.
shown in Table 1. In Groups 2, 3 and 4, peak left atrial appendage emptying flow velocity, left atrial appendage ejection fraction, systolic pulmonary venous flows velocity time integral were significantly lower, and left atrium was larger compared to Group 1. In Groups 3 and 4, peak systolic pulmonary venous flow velocity was slower than in that of Group 1. Significant difference was noted in peak left atrial appendage emptying flow velocity, peak systolic pulmonary venous flow velocity and velocity time integral between Groups 2 and 3. In Group 2, patients tended to have lower peak systolic pulmonary venous
flow velocity than that of normals but the difference didn’t reach statistical significance. There was a significant linear correlation between peak left atrial appendage emptying flow velocity and left atrial appendage ejection fraction (r50.62, P, 0.001, Fig. 1). A significant correlation was also noted between peak systolic pulmonary venous flow velocity and left atrial appendage function (Left atrial appendage ejection fraction: r50.67, P,0.001, Fig. 2; peak left atrial appendage emptying flow velocity: r50.58, P,0.001, Fig. 3). When normals were excluded from analysis, all the correlations were still
Fig. 1. Correlation between LAA ejection fraction (LAA EF) and maximum LAA emptying flow velocity (LAAvmx).
124
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
Fig. 2. Correlation between LAA ejection fraction (LAA EF) and peak systolic PVF velocity (PVFs).
Fig. 3. Correlation between maximum LAA emptying flow velocity (LAAvmx) and peak systolic PVF velocity (PVFs).
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
significant; r50.50, P50,001; r50.46, P50.003; r5 0.44, P50.005, respectively. There was also significant correlation between systolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.66, P50.001). When normals were excluded from analysis, the correlation was still statistically significant (r50.48, P50.002). There was no significant correlation between diastolic pulmonary venous flow velocity time integral and left atrial appendage ejection fraction (r50.12, P50.44; r50.11, P50.44 when normals excluded).
4. Discussion Left atrial appendage dysfunction has been described in patients with atrial fibrillation, with or without mitral stenosis but the left atrial appendage function is not well known in patients with mitral stenosis in sinus rhythm [1,2]. Jue et al. [10] first studied the possible relation of peak left atrial appendage emptying flow velocity to pulmonary venous flows, and concluded that left atrial appendage flow was independent of pulmonary venous flows. However, they included patients with severe mitral regurgitation which can affect both peak left atrial appendage emptying flow velocity and pulmonary venous flows because of the turbulent regurgitant jet. In recent experimental studies, it has been shown that removal of left atrial appendage decreases left atrial compliance and increases left atrial pressure at any given volume, and that left atrial appendage plays important role in left atrium reservoir function [3–5]. After removal of left atrial appendage in openchest dogs, Hoit et al. [4] demonstrated increases in the ratio of systolic pulmonary venous flow to diastolic pulmonary venous flow as an index of the relative reservoir to conduit function of the left atrium. In contrast, Tabata et al. [5] showed that systolic pulmonary venous flow significantly decreased and diastolic pulmonary venous flow significantly increased after left atrial appendage clamping in 15 patients during cardiac surgery. Recently, Ito et al. [11] studied left atrial appendage function in 23 patients with dilated cardiomyopathy and 25 patients with hypertrophic cardiomyopathy. In their study, patients with left atrial appendage dysfunction
125
tended to have a lower systolic pulmonary venous flow velocity and a higher diastolic pulmonary venous flow velocity than those with normal left atrial appendage function, but the differences didn’t reach statistical significance. The origin of the systolic pulmonary venous flow is less clear, and there is considerable disagreement in the literature. Some authors suggest that the systolic pulmonary venous flow is caused by pressure changes in the left atrium having suction effect [12– 14]. Several other experimental studies in dog models conclude that systolic pulmonary venous flow is generated predominantly by transmission of the right ventricular pressure pulse through the pulmonary vascular bed [15–18]. Smiseth et al. [19] have suggested that systolic pulmonary venous flow appears to be determined by right as well as left-sided cardiac effects. Nakatani et al. [20] have reported that a combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of left atrial function. In light of these findings, we evaluated pathological changes of the left atrial appendage in different groups of patients, who were expected to have left atrial appendage dysfunction, and we also investigated correlation between the left atrial appendage function and pulmonary venous flows pattern. The significant correlation we found between left atrial appendage ejection fraction and peak left atrial appendage emptying flow velocity indicates the left atrial appendage contractile function. The significant left atrial appendage dysfunction we also noted in Group 2 patients, as shown by the reduced peak left atrial appendage emptying flow velocity and left atrial appendage ejection fraction, suggests that the left atrial appendage function is not only influenced by atrial fibrillation but also by mitral stenosis itself. The significant correlation we found between peak left atrial appendage emptying flow velocity and peak systolic pulmonary venous flow indicates the relation of left atrial appendage emptying flow to the systolic phase of pulmonary venous flow. In our study, none of our patients had significant mitral regurgitation. On the other hand, the significant correlation between left atrial appendage ejection fraction and peak systolic pulmonary venous flow velocity in our study confirms that pulmonary venous flows pattern is influenced by left atrial appendage function. The
126
¨ et al. / International Journal of Cardiology 78 (2001) 121 – 126 T. Tukek
significant decrease in left atrial appendage ejection fraction, peak left atrial appendage emptying flow velocity together with systolic pulmonary venous flow velocity and velocity time integral in Groups 2, 3 and 4 in comparison with normal subjects also supports this concept. In their study, Paraskevaidis et al. [21] did not demonstrate relationship between atrial fibrillation and both peak systolic and diastolic pulmonary venous flow velocities but they did not investigate the effect of left atrial appendage function on pulmonary venous flows pattern. We also did not find significant decresase in peak diastolic pulmonary venous flow velocity in atrial fibrillation but there was significant decrease in both left atrial appendage function and peak systolic pulmonary venous flow velocity in Groups 3 and 4 patients. Therefore we thought that atrial fibrillation does not play significant role in the pathogenesis of pulmonary venous flows pattern but left atrial appendage function has important effect on systolic pulmonary venous flow. In conclusion, our results suggest that left atrial appendage is a contractile structure, and that left atrial appendage dysfunction has a detrimental effect on systolic phase of pulmonary venous flows which is thought to reflect left atrial compliance. Therefore left atrial appendage function needs to be taken into account when interpreting Doppler transmitral and systolic pulmonary venous flow patterns but further studies should be done to determine the potential contribution from reflected waves.
Acknowledgements ¨ for her excelWe gratefully thank Zahide Ac¸ikgoz lent technical aid in data collection.
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