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European Journal of Echocardiography 2003 4(4):272-278; doi:10.1016/S1525-2167(03)00003-9
© 2003 by European Society of Cardiology
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Copyright © 2003, The European Society of Cardiology

Evidence of atrial mechanical dysfunction by acoustic quantification in abnormal relaxation and restrictive filling patterns of diastolic dysfunction in patients with coronary artery disease

C.-M. Yu1, H. Lin1, L. C. C. Kum1, W.-F. Lam2, W.-H. Fung1 and J. E. Sanderson1

1Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
2Department of Medicine, Grantham Hospital, Hong Kong, People's Republic of China

Received 25 June 2002; received in revised form 2 January 2003; accepted after revision 3 January 2003.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Aim: This study made use of acoustic quantification (AQ) to investigate if left atrial (LA) mechanical function was impaired in patients with diastolic dysfunction, which might not be detected by conventional Doppler echocardiography.

Methods: One hundred and ten patients with coronary artery disease (mean age 65±11 years, 80% male) underwent echocardiography prospectively while AQ was performed using harmonic imaging at the apical four-chamber view to evaluate LA function.

Results: By Doppler echocardiography, left ventricular (LV) diastolic dysfunction in the form of abnormal relaxation pattern (ARP) was present in 84, pseudonormal (PN) in nine and restrictive filling pattern (RFP) in 10 patients. LA mechanical dysfunction with impaired total fractional area change (FAC) of ≤20% was present in 17/19 (89%) patients in the RFP/PN group, but was observed in 27/84 (32%) patients with ARP. Despite identical diastolic Doppler indices between patients with ARP with preserved (n=57) and impaired total FAC, the latter group had significantly lower LV ejection fraction (P<0.001), larger LV volumes (P<0.05 and 0.002, respectively), as well as larger LA area (P<0.001) and lower LA peak emptying and filling rates (both P=0.001). In contrast, there was no difference in nearly all of the parameters of LA function, LV systolic function and LV volume between patients with RFP/PN and ARP with FAC ≤20%. Both active and passive LA pump functions were impaired in patients with RFP/PN or ARP with FAC ≤20%.

Conclusion: LA mechanical dysfunction was found to be present in one-third of the patients with ARP of diastolic dysfunction despite a high MV-A. It was also present in almost all the patients with RFP/PN pattern of diastolic dysfunction. Therefore, AQ may provide information on atrial mechanical function complementary to that of Doppler echocardiography.

Keywords: acoustic quantification; echocardiography; left atrial function; left ventricular filling


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Diastolic function is an integral part in the assessment of left ventricular (LV) function. It consists of early diastolic phase, which depends on LV relaxation and late-diastolic phase, which relies on active atrial contraction[1]. Indices of early diastolic function have been well developed by both invasive and non-invasive means[2]. On the other hand, direct assessment of left atrial (LA) mechanical function remains difficult, and quantitative evaluation remains a clinical challenge. Invasive assessment of LA function is limited by the risk of performing atrial septal puncture, and unlike the assessment of early diastolic function, there is no widely accepted gold-standard parameter of atrial contractility. For non-invasive assessment of LA function, Doppler echocardiography has been used to assess transmitral atrial filling velocity pattern. This parameter was proven to be useful when there was no gross evidence of LV systolic dysfunction, such as after cardioversion for patients with paroxysmal atrial fibrillation[3,4]. However, the assessment of transmitral atrial filling velocity only reflects the atrioventricular gradient between two chambers rather than LA mechanical function per se[1]. In fact, in patients with diastolic dysfunction, it remains unclear whether atrial mechanical dysfunction is present, especially in patients with abnormal relaxation pattern (ARP). We hypothesized that atrial mechanism function is impairment in patients with LV diastolic dysfunction, which may not be detected by conventional Doppler echocardiography. To testify the hypothesis, acoustic quantification (AQ) was chosen to assess LA mechanical function in a cohort of patients with coronary artery disease. This echocardiographic tool has been validated against a variety of techniques, such as left ventriculogram[5,6], radionuclide ventriculography[7], cardiac MRI[8] and ultrafast computed tomography[9], and was shown to be useful in assessing LA function to differentiate between sinus rhythm and atrial fibrillation[10].


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Study population and design
One hundred and twenty-two consecutive patients with coronary heart disease were recruited in an echocardiography clinic. In 12 patients, the image quality was deemed unsatisfactory for AQ analysis and they were, therefore, excluded from the study. Of the remaining 110 patients, 63% had recent myocardial infarction (51% Q wave and 12% non-Q infarction), 37% had hypertension and 35% had diabetes mellitus. Echocardiography with conventional two-dimensional, M-mode and Doppler measurements was performed (Philips, Boston, MA, USA). AQ was performed using harmonic imaging at the apical four-chamber view to evaluate LA and LV function. Patients were excluded if they had atrial fibrillation or significant aortic and mitral valvular lesions, especially mitral valve disease.

Echocardiography
Ultrasound imaging was performed with a 2–4 MHz transducer (Philips, Boston, MA, USA). Standard two-dimensional and M-mode echocardiography study was performed according to the guidelines of American Society of Echocardiography[11,12]. LV diastolic function was assessed by Doppler echocardiography as previously described[13]. Patients were classified as having LV diastolic dysfunction according to the following criteria: restrictive filling pattern (RFP) was defined as E/A ratio ≥2 or equal to 1 to 2 and DT <140 ms; ARP was defined as E/A ratio <1 or equal to 1 to 2 and DT <240 ms; and pseudonormal (PN) pattern was defined as normal transmitral pattern, but abnormal pulmonary venous flow profile (reverse in systolic to diastolic forward flow ratio or increased atrial reversal velocity)[13–16]. At least three consecutive beats were measured and the average values were taken.

To assess cardiac function by AQ, the gain controls, including total and lateral gain and temporal gain compensation, were adjusted to optimize tracking of the endocardial border, and a region of interest surrounding the LV or LA cavity at apical four-chamber view was then defined. Harmonic imaging was used to optimize endocardial visualization[17]. Digital images were reviewed on-line with the continuous-loop review mode of the echocardiographic system to ensure accurate tracking of the endocardial border. The AQ parameters based on signal-averaging of five to six beats were obtained automatically when the images were steady[18]. The measurements were performed by the same operator to eliminate interobserver variability. The AQ-derived instantaneous volume/area and the change in volume/area over time waveforms were displayed together with the ECG tracing. In the LV, parameters measured included end-diastolic volume, end-systolic volume, ejection fraction and peak emptying rate. For the LA, parameters measured included the largest LA area during rapid atrial filling at the end of ventricular systole (LA-FA), the smallest LA area after atrial emptying at end of ventricular diastole (LA-EA), total fractional area change (FAC) of LA, the FAC as passive pump, active pump and conduit functions[19], as well as atrial peak filling rate (LA-PFR) and peak emptying rate (LA-PER).

Statistical analysis
Statistical analysis was performed using a statistical software program (SPSS for Windows, Version 10.1, SPSS Inc., Chicago, IL, USA). Linear regression analysis was used to calculate the correlation between parametric measurements. Unpaired t-test was used to compare the differences in mean between two continuous parameters. Since the mean age was not different among the sub-groups compared, statistical adjustment was considered unnecessary. Data were expressed as mean ± standard deviation. A P value of <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The mean age was 65±11 years, with 80% male. The mean heart rate was 68.6±13.4 beat/min. The mean systolic and diastolic blood pressure were 127±21 and 74±12 mmHg, respectively. The mean body weight was 63±11 kg and the body mass index was 24.3±3.5 kg/m2. LA function was successfully measured in all the 110 patients who underwent AQ assessment. The relationship between the change of LA size and atrial mechanical function is shown in Table 1. LA enlargement correlated with impairment of LA function. Such relationship is better reflected by the LA area than LA diameter by M-mode measurement (Table 1).


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  		Table 1 Correlation between various LA parameters measured by AQ and M-mode echocardiography.

 
LA mechanical dysfunction in patients with LV diastolic dysfunction
Transmitral Doppler study revealed, 6% (n=7) had a normal pattern in diastole, 77% (n=84) had an ARP, 8% (n=9) had a PN pattern while 9% (n=10) had a RFP of diastolic dysfunction. As RFP and PN patterns (n=19) are representing more severe diastolic dysfunction[20], they were compared with those with ARP or normal pattern (n=91). Patients with a RFP/PN pattern had significantly larger LA-EA (16.1±6.0 vs 9.0±4.3 cm2, P<0.001), LA-FA (18.5±6.5 vs 12.7±4.8 cm2, P=0.001) as well as lower total FAC (12.5±8.1 vs 31.3±16.2%, P<0.001), LA-PER (1.6±1.1 vs 4.1±2.9 EDA/s, P<0.001) and LA-PFR (1.9±1.2 vs 4.6±2.9 EDA/s, P=0.005) than those with an ARP or normal pattern.

According to transmitral diastolic filling, RFP/PN patterns of diastolic dysfunction were almost exclusively found in those with impaired total FAC of ≤20% (17 out of 44), and rarely in patients with preserved total FAC (2 out of 66) (39 vs 3%, {chi}2=14.3, P<0.001). On the other hand, 32% (27 out of 84) of patients with an ARP also had impaired FAC. The relationship between total FAC and diastolic function was studied by stratifying patients into those with impaired total FAC (≤20%) (n=44) and preserved total FAC (>20%) (n=66). When the patients with ARP and FAC <20% (n=57) were compared with those with APR and FAC ≤20%, the latter group had significantly lower ejection fraction (P<0.001) and larger LV volumes (P<0.05 and 0.002, respectively) (Table 2). In addition, the LA-EA was significantly larger (P<0.001), and the atrial peak emptying and filling function were poorer in those with impaired total FAC (both P=0.001) (Fig. 1). In patients with impaired total FAC, both the atrial passive and active pump functions were impaired (Table 2).


Figure 1
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  		Figure 1 Comparison of (A) left atrial area after peak atrial emptying (LA-EA), (B) left atrial peak emptying rate (LA-PER), and (C) the transmitral peak atrial filling velocity (MV-A) between patients with ARP of diastolic dysfunction with a FAC of <20%, patients with ARP and a FAC of ≤20% and those with RFP or PN pattern in diastole. *Denotes significant difference when comparing with ARP with a FAC of <20%. {dagger}Denotes significant difference when comparing with RFP or PN. See Table 2 for probability values.

 


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  		Table 2 Comparison of LA function and LV systolic and diastolic parameters in patients with ARP of diastolic dysfunction with preserved (>20%) and impaired (≤20%) LA total FAC as well as those with RFP or PN pattern in diastole.

 
When patients with RFP/PN were compared with those with ARP and total FAC ≤20%, interestingly, there was no difference in any of the parameters of LA function except a shift into predominantly conduit function. The LV systolic function and volumes were comparable (Table 2, Fig. 1). Fig. 2 shows typical measurement of FAC in patients with various degree of diastolic dysfunction and atrial mechanical dysfunction.


Figure 2
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  		Figure 2 Assessment of LA function by AQ. The change in LA area with time was plotted and displaced. (A) A patient with an ARP of diastolic dysfunction by Doppler echocardiography shows a high FAC of 35% by AQ. (B) Another patient with an ARP of diastolic dysfunction, but the FAC was reduced to 15%. (C) A patient with a RFP of diastolic dysfunction shows a reduced FAC to 10%. Note also the LA enlargement in this patient.

 
The relationship between total FAC (r=0.40, P<0.001), LA-PER (r=0.44, P<0.001) and LA-EA (r=–0.44, P<0.001) with LV ejection fraction by AQ is only modest.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Non-invasive assessment of atrial mechanical function was found to be difficult previously. This is especially limited by the lack of good indices that can detect both the change in atrial size and atrial contractility. Transmitral pulse-Doppler atrial filling velocity has been used as an index of atrial function[3,4,21], though it is more dependent on the pressure gradient across the mitral ring, and hence reflects the hemodynamics between the atrium and the ventricle during late-diastolic phase rather than atrial mechanical function[1]. Similarly, the calculation of the atrial ejection force is based on the transmitral atrial filling velocity and hence suffers from the same limitation[22]. An alternative approach to assess LA function is to measure the atrial areas and calculate the FAC, a method analogous to the measurement of end-diastolic and end-systolic volumes and ejection fraction for the LV[23]. The advancement of AQ allows a quick and automatic assessment of atrial area and total atrial function by averaging the measurement of multiple beats[10]. The peak atrial emptying rate, another parameter of atrial contractile function, can also be measured by AQ. In addition, the peak atrial filling rate during ventricular systole also reflects atrial compliance in addition to the intra-atrial pressure. The use of AQ to assess atrial function has been validated in the previous studies[10,24].

The present study found that atrial mechanical dysfunction is characterized by the presence of LA enlargement, which was associated with the reduction of atrial contractility as illustrated by the impaired total FAC and LA-PER. This is compatible with the previous observations that enlargement of LA was associated with depressed atrial emptying function and hence a slow recovery of atrial mechanical function after cardioversion[23]. Further analysis found that in these patients, both atrial active and passive pump functions were impaired. In relation to diastolic dysfunction, our results showed that significant atrial dysfunction characterized by the significant reduction of total FAC was present in almost all the patients with RFP, and one-third of those with ARP. In those with ARP and FAC ≤20%, all other parameters of atrial function were impaired to the same extent as those with RFP/PN pattern. Intriguingly, all the Doppler diastolic indices are identical between the patients with ARP having a preserved and impaired FAC. In other words, atrial mechanical dysfunction with atrial enlargement is present in some patients with an ARP of diastolic dysfunction even when the transmitral atrial velocity appears to be normal or even ‘compensatory increased’. Supplementary information may also be revealed by studying the atrial reversal flow of pulmonary vein. We believe that the transmitral flow velocity curve only reflects the atrioventricular pressure gradient between the LA and the LV during different periods of the cardiac cycle. Patients with ARP and impaired atrial function might be ‘compensated’ in transmitral atrial velocity by an elevated atrial pressure, which will maintain the transmitral gradient and hence atrial velocity across the mitral valve. In the presence RFP or PN pattern, the shifting from pumping function into conduit function is likely to reflect the progression of LA mechanical failure as previously suggested[25].

Impairment of total FAC was associated with a larger LV size and impaired LV systolic function when patients with ARP were compared with the patients with impaired and preserved FAC. Interestingly, the extent of impairment of LA and LV function is similar between the patients with ARP who had LA mechanical dysfunction and those with PRF or PN pattern of diastolic dysfunction. On the other hand, the correlation between total FAC and LV ejection fraction is only modest. Therefore, the occurrence of atrial mechanical dysfunction in some patients with ARP could partially be explained by the underlying impairment of LV systolic function. In addition, in the presence of coronary artery disease, atrial mechanical function could be depressed by ischemia[26].

Limitation and clinical implication of the study
The assessment of atrial function by AQ is dependent on image quality. Therefore, it may not be feasible on every patient. On the other hand, in suitable subjects, quantitative AQ may help to provide supplementary information on the conventional transmitral Doppler examination, especially for atrial function. It may also provide additional insight into the relationship between hemodynamic changes across the atrioventricular valve and underlying atrial mechanical dysfunction so as to understand the pathophysiological changes in the development of diastolic dysfunction. It will also be interesting to study atrial function by AQ on other cardiac disease models.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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