|Year : 2019 | Volume
| Issue : 2 | Page : 198-206
Effect of left atrial functions upon the functional capacity in patients with systolic heart failure
Layla A Mohammed, Nadia A Agiba, Asmaa A Aly
Department of Cardiology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt
|Date of Submission||04-Jun-2019|
|Date of Decision||17-Jun-2019|
|Date of Acceptance||10-Jul-2019|
|Date of Web Publication||23-Oct-2019|
Nadia A Agiba
Department of Cardiology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo 11517
Source of Support: None, Conflict of Interest: None
Objective To assess left atrial (LA) function and its effect upon the functional capacity in patients with systolic heart failure (HF) using the two-dimensional (2D) speckle tracking echocardiography (STE).
Patients and methods This study included 44 patients with systolic HF, ejection fraction less than 40%, sinus rhythm, and New York Heart Association (NYHA) class II–IV. All patients underwent six-minute walk test and conventional, tissue Doppler imaging (TDI), and 2D-STE echo. LA measures included LA dimensions and volumes for calculation of reservoir, conduit, and contractile functions. Peak atrial longitudinal strain (PALS) and peak atrial contractile strain were measured by 2D-STE. Based on NYHA class, patients were divided into group 1 (patients with NYHA II) and group 2 (patients with NYHA III–IV).
Results There were no significant differences between both groups regarding demographic data. The 2D ejection fraction was significantly lower in group 2 compared with group I (P<0.05). Group 2 had significantly lower average LA peak systolic velocity (S′) and average LA late diastolic velocity (a′) by TDI compared with group 1, and also group 2 had significantly lower average PALS (16.3±7.2 vs. 11.3±4.4) and average peak atrial contractile strain (10.7±5.4 vs. 5.8±3.3, respectively; P<0.001), compared with group I. There were negative correlations between NYHA class and PALS (r=−0.436, P=0.003), whereas a positive correlation for PALS with six-minute walk distance (r=0.632, P=0.000). PALS was the most significant parameter that can predict limited exercise capacity.
Conclusion LA mechanical functions were decreased in patients with systolic HF either measured by STE or TDI. PALS measured by 2D-STE is the most significant parameter correlated with functional capacity.
Keywords: exercise capacity, heart failure, LA function, six-minute walk test, speckle tracking echocardiography
|How to cite this article:|
Mohammed LA, Agiba NA, Aly AA. Effect of left atrial functions upon the functional capacity in patients with systolic heart failure. Al-Azhar Assiut Med J 2019;17:198-206
|How to cite this URL:|
Mohammed LA, Agiba NA, Aly AA. Effect of left atrial functions upon the functional capacity in patients with systolic heart failure. Al-Azhar Assiut Med J [serial online] 2019 [cited 2019 Dec 7];17:198-206. Available from: http://www.azmj.eg.net/text.asp?2019/17/2/198/269766
| Introduction|| |
Heart failure (HF) is a complex clinical syndrome that can result from structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. As there is no definitive diagnosis for HF, it remains a clinical diagnosis that is largely based on a careful assessment of history and physical examination and supported by ancillary tests such as ECG, chest radiograph, and echocardiography . Exercise intolerance is one of the main symptoms of congestive heart failure (CHF), but the mechanisms responsible for limiting exercise capacity have not been completely clarified . Previous studies have demonstrated that left ventricular (LV) systolic function does not predict exercise capacity ,. In contrast, recent reports showed that LV diastolic dysfunction was intimately related to functional status ,. Although LV diastolic dysfunction is known to reduce exercise capacity, it is often difficult to predict precise exercise capacity by evaluating diastolic filling because hemodynamic parameters measured at rest are influenced by heart rate, loading condition, age, and the properties of the left atria (LA) and LV. LA function is closely related to LV diastolic filling; therefore, indices of LA function may predict exercise capacity in patients with LV dysfunction ,. However, LA function is difficult to assess quantitatively by conventional echocardiography. In this study, we sought to evaluate LA function by speckle tracking echocardiography (STE) and correlate between LA function and exercise capacity in patients with systolic HF.
| Patients and methods|| |
This study included 44 patients with clinical manifestation of systolic HF who were followed up at Cardiology Department of Al-Zahraa University Hospital, Faculty of Medicine, Al-Azhar University, Egypt, between January 2017 and March 2018 with the following inclusion criteria: patients with clinical manifestation of systolic HF, New York Heart Association (NYHA) (II–IV), and ejection fraction (EF) less than 40%. All patients were on optimum medical treatment of HF at the time of the study, which included β-blockers, ACE inhibitors, and diuretics. Medications were optimized for individual patients at least 2 weeks before enrollment, based on symptoms and renal function. All patients were in sinus rhythm at the time of the study. Patients with clinical evidence for cardiac decompensation, any rhythm disturbance, recent acute coronary syndrome, patients with significant valvular lesions, congenital heart diseases, and those with limited physical activity owing to factors other than cardiac etiology (e.g. arthritis), more than mild renal failure, chronic obstructive pulmonary disease, as well as stroke were excluded from this study.
Detailed patient history was taken from all the enrolled patients, and they all underwent physical examinations, including blood pressure, heart rate, and anthropometric measurements. Resting 12-lead ECG was recorded. Transthoracic echocardiographic examination was followed by six-minute walk test (6MWT) on the same day.
Informed consent forms were signed by every patient enrolled, and the study was approved by the local ethics committee of the Al-Azhar University School of Medicine.
Six-minute walk test
The test was performed by a cardiologist who was blinded to the results of echocardiography according to standard protocol . Patients were informed of the purpose and protocol of the test. We used a 20-meter flat free-obstacle corridor in our department. Patients were instructed to walk as far as they can, turning 180° after reaching the end of the corridor, during the allocated time of 6 min. Patients walked unaccompanied so as not to influence walking speed. Patient’s preparation and encouragement were done according to American Thoracic Society recommendation . The Borg scale was used before and after the test to record the level of fatigue and level of shortness of breath . All patients were instructed to keep their regular antifailure treatment before the test. The attending supervisor measured the total distance walked by the patient. Pulse and blood pressure were measured, and baseline dyspnea and fatigue were recorded for all patients using Borg scale . The test was terminated at the end of the 6 min or upon patient’s request or if the continuation of the test would have interfered with the patient’s safety . Immediately after termination of the test, the patient was allowed to rest on a nearby chair. The total distance walked was calculated, and heart rate was measured.
All echocardiographic measurements were obtained at rest. Standard echocardiographic examination and pulsed-wave Doppler and tissue-Doppler imaging were performed using Vivid E9 (GE Ultrasound, Horton, Norway) with a 2.5-MHz matrix probe (M5S) with the capability of tissue Doppler imaging (TDI) and gray-scale recording for speckle tracking study. We used the mean of all recordings from three consecutive cycles.
Echocardiographic assessment of left ventricle
This included M-Mode measurements of LV end-diastolic and end-systolic dimensions. LV ejection fraction was assessed by Teichholz method and modified Simpson’s method to measure LV end diastolic volume (EDV) and LV end systolic volume (ESV) in 4 chamber and 2 chamber views to get the biplane auto ejection fraction (EDV-ESV/EDV)x100 ([Figure 1]).
|Figure 1 Showed assessment of left ventricular systolic function using auto-ejection fraction biplane.|
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LV mass was calculated by the use of the Devereux formula and was indexed to body surface area.
Doppler echocardiography was used to measure mitral inflow velocity including the peak early filling (E), and late diastolic filling (A) velocities and the E/A ratio.
Tissue Doppler echocardiographic assessment of LV functions included annular systolic, early, and late diastolic velocities (SA, Ea, and Aa). TDI was obtained from four to two-chamber views to acquire the average mitral annular velocity from four sites (septal, lateral, anterior, and inferior). The obtained measurements included the average systolic annular tissue velocity (Av. Sa), average early diastolic annular tissue velocity (Av. Ea), and the average late diastolic annular tissue velocity (Av. Aa). E/Ea ratio [the ratio of peak early mitral inflow velocity to the average early diastolic annular tissue velocity (Av. Ea)] was calculated.
Two-dimensional speckle track echocardiography
The LV longitudinal strain was also assessed using 2D-STE analysis with QRS onset as the reference point, applying a commercially available strain software package to the LV on EchoPAC GE version 201 using the Automated Function Imaging software. Three points in the LV were anchored, apex, and annular hinge points in apical four-, three-, and two-chamber views. Then the system processed the data and after finishing tracing and auto-processing of the three views, the global strain and Bull’s eye report were obtained. Peak LV strain is the peak negative value that was obtained at or before aortic valve closure.
Left atrial assessment
- LA dimension was estimated in parasternal long-axis view from 2D targeted M-mode, with normal range of 2.0–4.0 cm.
- LA volume was estimated by the biplane area length method, using apical four and two-chamber views.
- Maximal LA volume was measured just before mitral valve opening at end systole (Vol-max). Minimal LA volume was measured at end diastole when mitral valve closed (Vol-min). Pre-contractile LA volume was measured at P-wave onset on ECG just before atrial contraction, if in sinus rhythm [pre-A LA volume (Vol-P)].
- LA volume index was calculated as LA volume divided by body surface area. Indexed to body surface area, the normal maximal LA volume is 22±5–6 ml/m2, minimal LA volume is 11±4 ml/m2, and pre-A LA volume is 15±5 ml/m2.
- LA functions were calculated from the following formula as follows:
- Reservoir function was calculated as LA expansion (LA max−LA min)/LA min×100%.
- LA conduit function was calculated as LA passive emptying fraction (LA max−LA pre A)/LA max×100%.
- LA contractile function was calculated as LA active emptying fraction (LA pre A−LA min)/LA pre A100%.
- LA function examination using Tissue Doppler including the following parameters:
- For the TDI velocity and strain, we used the two apical views (four and two-chambers views). For data acquisition, three complete cardiac cycles were collected and stored in a cine-loop format. The image sector width was set as narrow as possible to allow frame rate acquisition greater than 80 frames/s. Special attention was paid to the color Doppler velocity range setting to avoid any aliasing within the image.
- The TDI sample volume was placed at mid atrial segment of interest, usually about 2 mm for measuring velocity. Offline analysis of the digitally stored loops was done by trace profile displacement of the velocity to obtain the average peak LA systolic myocardial velocity, the average peak LA early diastolic myocardial velocity (Em velocity), and the average peak LA late diastolic myocardial velocity (Am velocity).
- LA longitudinal strain was assessed using 2D speckle-tracking analysis with QRS onset as the reference point, applying a commercially available LV strain software package to the LA (EchoPAC version 201 GE, Jaken Medical Inc. USA). The region of interest was adjusted to include the LA myocardium in both four and two-chamber views. The LA manual correction was performed to optimize tracking results if needed.
QRS-timed analysis was used to obtain peak atrial longitudinal strain (PALS), which is the first positive peak measured at the end of the reservoir phase, and peak atrial contraction strain (PACS), measured just before the start of the active atrial contractile phase, which is the second positive peak calculated by averaging values observed in all LA segments (global PALS and PACS). The analysis of the LA strain curve was done using QRS onset as the reference point to measure the following: peak atrial strain during ventricular systole (εS), which is measured just before mitral valve opening, and it is a surrogate of the reservoir function, and late peak strain just before the active atrial contractile phase (εCT) begins, at the onset of the P wave on the ECG, which is a surrogate of the contractile function.
The average LA strain was obtained after averaging the six segments in each view.
All speckle tracking measurement of both LA were performed offline ([Figure 2]).
|Figure 2 Assessment of left atrial functions using speckle tracking 2-D of the left atrial to measure peak left trial global longitudinal strain (LAGLS).|
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Statistical analysis was performed using statistical package for the social sciences (SPSS, IBM company USA) version 23. Data are presented as the mean±SD value for continuous variables and as numbers and frequency percentages for categorical variables as descriptive analysis. Analytical analysis also was done for comparison between categorical variables by using the χ2-test. All continuous variables were passed through standard test for normality (Kolmogorov–Smirnov test). Comparisons of continuous variables between groups were made using the unpaired t-test for the normally distributed data and Mann–Whitney U-test was used to compare nonparametric data. Pearson and spearman correlation coefficients were used to evaluate the relationship between the six-minute walk distance (6MWD) and continuous variables. Multivariate regression analysis was also used. The level of significance was accepted if the P value was less than 0.05.
| Results|| |
This study was conducted on 44 patients having systolic HF (mean age 55.7±8.6 years, 79% were males). They were classified according to their NYHA functional class into two groups (group I, NYHA class II, and group II, NYHA class III/ambulatory class IV). The average NYHA class for the whole patients was 2.75±0.7, with a median of 3 and inter quartile range (IQR)=1. Both groups were age and sex matched.
There were no statistical significant differences between the two groups regarding the demographic data, BMI, or other clinical data ([Table 1]).
|Table 1 Clinical characteristics of whole patients and between the two groups according to New York Heart Association class|
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However, a significant difference was found regarding the functional capacity parameters measured by 6MWD between the two studied groups (P=0.00), being lower in group II ([Table 1]).
Comparison between the two groups regarding conventional echocardiographic parameters of LV function showed comparable results of LV functional parameters in the whole patients except the biplane EF and LV global longitudinal strain, which was significantly lower in group II compared with the group I (P<0.05; [Table 2]).
|Table 2 Comparison between groups regarding basic Echo-Doppler, tissue Doppler imaging, and two-dimensional speckle tracking echocardiography of left ventricular parameters|
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Regarding the LA functional parameters, there were no significant differences between both groups in relation to volumetric indices of the LA function ([Table 3]).
|Table 3 Left atrial volume and functions using two-dimensional echocardiography in whole group and between both groups|
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Regarding tissue Doppler imaging parameters of left atrial functions
Group II had significantly lower average LA peak systolic velocity (S′) and average LA late diastolic velocity (a′) of LA compared with group I. However, no significant difference was found in the average peak early diastolic velocity (e′) between both groups by TDI ([Table 4]).
|Table 4 Tissue Doppler of the left atrial of all patients and comparison between patient groups|
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Comparison between groups regarding left atrial strain measured by two-dimensional speckle track echocardiography
Significantly lower average peak LA longitudinal strain was measured by 2D-STE in group II compared with group I (16.3±7.2 vs. 11.3±4.4) and lower average peak LA contractile strain in group II compared with group I (10.7±5.4 vs. 5.8±3.3, respectively; P<0.001; [Table 5]).
|Table 5 Left atrial functions assessed by volumetric indices of all patients and comparison between both groups|
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Correlation of the New York Heart Association class with demographic data of the patients
Correlation between the NYHA functional class and the clinical data of the patient showed negative correlation with the 6MWD (r=−0.68, P=0.00), whereas no correlation with the age (r=−0.19, P=0.23; [Figure 3]).
|Figure 3 Correlation between New York Heart Association functional class and six-minute walk distance.|
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Correlation of the NYHA functional class with echocardiographic parameters:
There were negative correlations between the NYHA class and PALS (r=−0.436, P=0.003) PACS (r=−0.48, P=0.001), and LV global longitudinal strain (r=−0.30, P=0.05; [Figure 4]).
|Figure 4 Correlation between New York Heart Association functional class and peak atrial longitudinal strain (PALS).|
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Correlation of the PALS with different echocardiographic parameters:
There was a positive correlation between PALS and the average LV annular peak systolic velocity (S′) (r=0.35, P=0.019) and LA late peak atrial diastolic velocity (LA a′) (r=0.367, P=0.014).
Predictors of limited six-minute walk distance
From the different echo-Doppler parameters in multivariate regression analysis, only the PALS [4.5 (0.433–8.7), P=0.031] independently predicted limited 6MWD ([Table 6]).
|Table 6 Multivariate regression analysis for prediction of limited six-minute walk distance|
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| Discussion|| |
HF is a major public health problem  with high morbidity and mortality . LV systolic dysfunction is the commonest cause of HF symptoms. Despite recent advances in pharmacological and device treatment, HF prognosis and quality of life (QoL) remain poor ,. HF affects QoL more profoundly than many other chronic diseases . Moreover, the QoL decreases as NYHA class worsens . Therefore, exercise intolerance is the key factor.
LA function is closely related to LV diastolic filling; therefore, indices of LA function may predict exercise capacity in patients with LV dysfunction.
In this study, we thought to evaluate the LA function by different echocardiographic modalities in patients with systolic HF and to evaluate the correlation between LA function and exercise capacity.
Of the 44 patients with systolic HF enrolled in this study, 18 patients (group I) were in NYHA functional class II, and 26 patients (group II) were in NYHA class III/ambulatory class IV.
The results of this study demonstrated a significant difference between both groups regarding LV ejection fraction assessed by biplane area method, being lower in group II. This result is consistent with a previous study  that studied 36 patients diagnosed with CHF by echocardiography, and it reported that the average ejection fraction was significantly higher in group 1 patient (NYHA I–II) compared with group II (NYHA III–IV) (44.84±8.04 vs. 32.59±11.48% with P=0.0007).
On the contrary, our results did not correlated with data from previous studies ,, which concluded that the LV systolic function does not predict exercise capacity.
Recent reports showed that LV diastolic dysfunction was intimately related to functional status ,. Although LV diastolic dysfunction is known to reduce exercise capacity, it is often difficult to predict precise exercise capacity by evaluating diastolic filling because hemodynamic parameters measured at rest are influenced by age, heart rate, loading condition, and the properties of the LV and LA. LA function is closely related to LV diastolic filling; therefore, indices of LA function may predict exercise capacity in patients with LV dysfunction ,.
Regarding volumetric indices of LA functions, we did not find significant differences between both groups either in LA reservoir, conduit, or contractile function as assessed by conventional echo.
These findings are discordant with the results of Terzi et al.  and Donal et al. , who found that increased LA sizes and decreased LA function at rest were associated with decreased peak VO2 and with a higher NYHA class, lower exercise capacity, and shorter exercise time in patients with HF.
This asymmetry could be explained by the small number of patients included in our study. It is possible that if we had a higher number of patients, then the parameters would be significant.
Moreover, there are many factors that can affect the LA size or volume . For this reason, LA volume could not be used solely to represent the mechanical function of LA.
In this study, we demonstrated decreased LA mechanical function as assessed by TDI with significantly lower average LA peak systolic velocity (S′) and average LA late diastolic velocity (a′).
This result is in accordance with the results of Tsai et al. , who found significant decrease in LA tissue velocity in patients with CHF, but they did not correlated this findings with the patients’ NYHA class.
In terms of strain parameters measured by 2D-STE, group II patients had significantly lower values of LA strain parameters, namely, PALS and PACS, compared with group I.
Numerous studies had confirmed the strong association between LA function and the functional capacity. 2D-STE of LA strain has shown to be an independent predictor of exercise capacity in both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Kusunose et al.  and D’Andrea et al.  demonstrated that PALS was an independent predictor of estimated metabolic equivalents in patients with HFpEF and HFrEF.
Similar result was reported by Ahmed et al.  who found significant decrease in LA strain parameter of LA function assessed by 2D-STE in patients with systolic HF.
It is likely that intrinsic problems with LA myocardial contractility such as LA fibrosis or ischemia play a role and may also be mediated by the increased work load imposed on LA myocardium because of increased LV diastolic stress, which over time may lead to intrinsic LA dysfunction and gradual decrease in LA contribution in LV filling .
In this study, we found a strong negative correlation between NYHA class and 6MWT. Yap et al.  in their systemically analyzed study on the correlation between NYHA class and 6MWD demonstrated the subjectivity of the NYHA classification when compared with a more objective measure like the 6MWD, with the 6MWD in all NYHA classes showing significant heterogeneity across different studies. Despite this heterogeneity, worsening NYHA class status appears to correlate well with the decreasing 6MWD between class II and III and between class III and IV also there was a significant difference between group I and II regarding their 6MWD where group 2 had significantly lower 6MWD than group 1 (p=0.000) [Table 1]. In other words, NYHA class appears useful for discriminating between mild and severe HF.
On the contrary, Rostagno et al.  published a prospective study that compared different methods of functional capacity in patients with CHF, and they concluded that in patients with CHF a poor relation exists between clinical methods of functional evaluation such as NYHA classification and the results of cardiovascular functional test (cardiopulmonary exercise test and 6MWT) or between the functional tests themselves.
Although NYHA classification is to some degree subjective, it is still an easily applied first‐line tool in everyday clinical practice to assess patients’ functional limitation. Moreover, in more symptomatic patients (NYHA III/IV), the NYHA classification appears to be a well‐performing, accurate clinical tool to estimate these patients’ functional limitation and guide therapy.
There are several mechanisms that explain the relationship between exercise capacity and function of LA. LA function reflects LV diastolic filling and therefore predicts cardiac output and stroke volume response to exercise . Reduced LA function may contribute to a decrease in preload and stroke volume of LV according to the Frank-Starling mechanism ,. After combined atrial and ventricular dysfunction, the mean pulmonary arterial pressure increases more significantly in comparison with isolated atrial or ventricular dysfunction . As a result of increased right ventricular afterload, the right ventricular output is decreased, which leads to decreased LV filling and cardiac output .
In this study, the PALS and PACS negatively correlated with NYHA class. This result is consistent with Ahmed et al. , whereas all parameters of LA (reservoir and contractile) function assessed by strain showed a negative correlation with NYHA class and the severity of HF symptoms increases with the severity of LA dysfunction.
Bilen et al.  reported a significant negative correlation between NYHA and LA reservoir and pump functions (left atrial ejection fraction (LAEF) and left atrial appendage ejection fraction (LAAEF)), but no significant correlation with conduit function.
Similarly, Ahmed et al.  concluded that the LA parameters (PALS and PACS) in all LA walls were significantly negatively correlated with the NYHA class. The small sample size is considered a limitation for application of our research and needs to be applied on a large number of patients with systolic HF and include more patient with ischemic etiology and dilated myopathy to allow differentiation according to their etiology of HF.
| Conclusion|| |
LA mechanical function was impaired in patients with systolic HF either measured by STE or TDI. The PALS measured by 2D-STE is the most significant parameter correlated with functional capacity in patients with systolic HF.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]