Left Atrial Contractility in Ischemic Heart Disease Patients with Left Ventricular Systolic Dysfunction.

BACKGROUND: Left atrial (LA) active emptying plays an important role in left ventricular (LV) filling. It not only depends on LA preload but also on LA contractility. Our aim was to assess LA wall contraction velocity (LAWV) and its relation to each of LA active stroke volume index (LAASVI) and LA active emptying fraction (LAAEF) as markers of LA active emptying in patients with ischemic heart disease (IHD) and impaired LV systolic function.
METHODS: We studied 50 consecutive patients with stable IHD and LV ejection fraction <45% and 50 healthy controls. Standard echocardiography assessed: Biplane LV volumes and ejection fraction, trans-mitral Doppler E and A wave velocities and E/A ratio, indexed biplane LA volumes pre- and post-atrial contraction, LAASVI and LAAEF. LAWV was measured by tissue Doppler imaging.
RESULTS: Trans-mitral Doppler A velocity was lower in the study group 60.64 ± 20.6 vs 72.46 ± 17.13 cm/s (P = 0.002). Accordingly, E/A ratio was higher in the study group 1.32 ± 0.78 vs 0.92 ± 0.3 (P < 0.0001). Indexed biplane LAV-pre atrial contraction was larger in the study group 23.61 ± 3.8 vs 17.16 ± 3.57mL/m2 (P < 0.0001). Indexed biplane LAV-post atrial contraction was larger in the study group 16.22 ± 4.14 vs 13.19 ± 3.56mL/m2 (P=0.0002). Accordingly, biplane LAASVI was higher in the study 53 group 7.9 ± 1.26 vs 3.96 ± 0.63 mL/m2 (P < 0.0001). LAAEF was larger in the study group 32.37 ± 8.89 vs 24.31 ± 7.12% (P < 0.0001). LAWV was lower in the study group 6.78 ± 0.51 vs 10.58 ± 0.67 cm/sec (P < 0.0001).
CONCLUSION: In patients with IHD and impaired LV systolic function, LA wall contractility is reduced. However, LAASVI and LAAEF are enhanced.

INTRODUCTION

Left atrial (LA) active emptying during late left ventricular (LV) diastole plays an important role in LV filling, especially in patients with hypertension, myocardial infarction, or heart failure (HF). Studies have constructed pressure–volume curves for the LA in patients with myocardial infarction and found that the LA contribution to LV function depends on the Frank–Starling mechanism.[1]

Active LA emptying not only depends on the LA preload before contraction but also on LA contractility. This is evident in patients with HF when the LV diastolic pressure (afterload) increases which may affect LA contractility.[2]

The ventricular myocardial contraction velocity in various heart diseases has been evaluated as one of the indices of myocardial contractility using tissue Doppler echocardiography.[3] Similar to it, the LA wall contraction velocity (LAWV) may be an indicator of LA contractility during atrial contraction. It was previously reported that LAWV correlates with the LA appendage flow velocity and fractional shortening; this suggests that LAWV is a marker of LA contractile function. The role of LAWV in LA emptying has been studied using tissue Doppler echocardiography in patients with hypertrophic cardiomyopathy.[4]

The purpose of this study was to assess LAWV measured by tissue Doppler imaging and its role of as a marker of LA active emptying in patients with ischemic heart disease and impaired LV systolic function.

MATERIALS AND METHODS

A total of 100 subjects presenting to the echocardiography unit at Ain Shams University were studied in the period from January 2014 to November 2104. These were 50consecutive patients (study group) and 50 healthy subjects (control group). Selected patients had stable ischemic heart disease with LV ejection fraction (LVEF) <45% (as assessed by Simpson's method of discs) who were in New York Heart Association (NYHA) class II or III on optimal recommended pharmacological therapy.

Ischemic heart disease was defined as a history of myocardial infarction or acute coronary syndrome more than 30 days prior to enrollment or history of percutaneous coronary intervention or coronary artery bypass grafting.

Patients were excluded from the study if they were found to have a rhythm other than sinus; left bundle branch block morphology or intraventricular conduction delay on electrocardiogram (ECG); mitral stenosis of any grade or mitral regurgitation more than grade I/IV; overlapped transmitral Doppler E and A waves; history of mitral valve repair or replacement; preexisting pulmonary disease and pulmonary hypertension of any etiology.

The control group consisted of 50 healthy age- and gender-matched volunteers who had no history of hypertension, diabetes mellitus, or heart disease. The study was approved by the medical research ethical committee of Ain Shams University; all subjects gave informed consent to participate in the study.

Standard transthoracic echocardiography

Standard transthoracic echocardiography using machine-integrated ECG recording was performed using a Vivid S5 machine with an M3S matrix sector array probe with a frequency range from 1.7 to 3.2 MHz (GE Vingmed, Horten, Norway). A comprehensive echocardiographic study following standardized protocols was performed for all subjects by an echocardiographer accredited by the European Association of Echocardiography. The following measurements were obtained: Biplane LV volumes and LVEF using the modified Simpson's method of discs according to recommendations of the American Society of Echocardiography,[5] transmitral Doppler E and A wave velocities and the E/A ratio.

Echocardiographic assessment of the left atrium

LA dimension was measured using two-dimensional (2D) guided m-mode echocardiography in the parasternal long axis view, biplane LA volumes pre- and post-atrial contraction (LAV-pre and LAV-post) were measured by the modified Simpson's method of discs according to recommendations of the American Society of Echocardiography[5] as follows:

LA endocardial border was traced in apical 4- and 2-chamber views with a straight line traced between the attachment points of the mitral annulus with the valve leaflets. The LA appendage and the pulmonary veins confluence were excluded from the LA tracings.

Biplane LAV-pre contraction was measured at the beginning of the P-wave while biplane LAV-post contraction was measured at the beginning of the QRS complex with the closure of the mitral valve.

The acquired volumes were then indexed to body surface area to calculate the biplane active LA active stroke volume index (LAASVI) calculated as LAV-pre-LAV-post and LA active emptying fraction calculated as (LAASVI/LAV-pre) ×100.[6]

Left atrial wall contraction velocity by tissue Doppler imaging

LAWV was measured in the apical long axis view using pulsed-wave tissue Doppler imaging with the region of interest placed near the basal posterior wall of the LA. The peak positive wave obtained during atrial contraction (Sm) was measured.

Statistical analysis

Data were statistically analyzed using SPSS statistical package version 17 (SPSS Inc., Chicago, IL, USA). Categorical variables were expressed as number and percentage and analyzed using Chi-square test. Continuous variables were expressed as mean ± standard deviation; Student's t-test and Pearson's correlation coefficient were used as appropriate. Multivariate analysis was done by multivariate linear regression analysis test. P < 0.05 was considered statistically significant and P < 0.0001 was considered highly significant.

RESULTS

The examined population (n = 100) was divided into a study group (n = 50) and an age- and gender-matched control group (n = 50). There was no statistically significant difference between both groups regarding baseline characteristics of age, gender, distribution, and smoking status [Table 1]. However, as expected a significant difference was present regarding the presence of type II diabetes mellitus and hypertension (P < 0.0001 for both) as we chose the control group subjects to be nondiabetic and nonhypertensive.

Table 1

Baseline characteristics

Clinical characteristic	Study group (n = 50)	Control group (n = 50)	P
Age (years)	57.5±5.1	58.3±4.6	0.438
Male gender, n (%)	34 (68)	36 (72)	0.663
Weight (kg)	82.9±9.8	83.7±9	0.689
Height (m)	1.67±0.1	1.69±0.05	0.128
BSA (m2/kg)	1.92±0.14	1.94±0.11	0.272
Smoking, n (%)	20 (40)	14 (28)	0.205
Hypertension, n (%)	45 (90)	0 (0)	<0.0001
Diabetes mellitus (type II), n (%)	33 (66)	0 (0)	<0.0001

Continuous variables are expressed as mean and standard deviation; whereas categorical variables are expressed n (%). BSA = Body surface area

Echocardiographic measurements

LVEF was significantly lower in the study group 39.08% ± 5.58% versus 62.26% ± 5.42% in the control group (P < 0.0001). However, there was no significant difference between the study and control groups regarding LA dimension 35.2 ± 13.5 mm versus 34.1 ± 2.6 mm, respectively (P = 0.58).

The transmitral Doppler A velocity was significantly lower in the study group 60.64 ± 20.6 cm/s versus 72.46 ± 17.13 cm/s in the control group (P = 0.002). However, there was no significant difference between the study and control groups regarding the transmitral Doppler E velocity 67.84 ± 21.03 versus 64.06 ± 18.43 cm/s, respectively (P = 0.342). Accordingly, transmitral Doppler E/A ratio was significantly higher in the study group 1.32 ± 0.78 versus 0.92 ± 0.3 in the control group (P < 0.0001) [Table 2].

Table 2

Echocardiographic measurements

Echocardiographic measurement	Study group (n = 50)	Control group (n = 50)	P
LVEF (%)	39.08±5.58	62.26±5.42	<0.0001
Left atrium (mm)*	35.18±13.49	34.10±2.62	0.580
Transmitral Doppler E-velocity (cm/s)	67.84±21.03	64.06±18.43	0.342
Transmitral Doppler A-velocity (cm/s)	60.64±20.60	72.46±17.13	0.002
Indexed biplane LAV-pre (mL/m2)	23.61±3.8	17.16±3.57	<0.0001
Indexed biplane LAV-post (mL/m2)	16.22±4.14	13.19±3.56	0.0002
Biplane active stroke volume index (mL/m2)	7.38±1.26	3.96±0.63	<0.0001
Left atrial active emptying fraction (%)	32.37±8.89	24.31±7.12	<0.0001

Continuous variables are expressed as mean and standard deviation. *Left atrium dimension in millimeters measured from the parasternal long axis view by m-mode. LAV-pre = Pre-atrial contraction volume of the left atrium, LAV-post = Post-atrial contraction volume of the left atrium, LVEF = Left ventricular ejection fraction

Echocardiographic assessment of the left atrial volumes and function

Indexed left atrial volumes

Indexed biplane LAV-pre was significantly larger in the study group 23.61 ± 3.8 mL/m2 versus 17.16 ± 3.57 mL/m2 in the control group (P < 0.0001). Furthermore, indexed biplane LAV-post was significantly larger in the study group 16.22 ± 4.14 mL/m2 versus 13.19 ± 3.56 mL/m2 in the control group (P = 0.0002).

Left atrial active stroke volume index

Accordingly, biplane LAASVI was significantly higher in the study group 7.39 ± 1.26 mL/m2 versus 3.96 ± 0.63 mL/m2 in the control group (P < 0.0001).

Left atrial active emptying fraction

LA active emptying fraction was significantly larger in the study group 32.37% ± 8.89% versus 24.31% ± 7.12% in the control group (P < 0.0001) [Table 2].

Left atrial wall contraction velocity

LA wall systolic wall motion velocity (LAWV) was significantly lower in the study group 6.78 ± 0.51 cm/s versus 10.58 ± 0.67 cm/s in the control group (P < 0.0001).

Correlating preload and left atrial contractility (active emptying)

Biplane indexed LAV-pre (representing preload) had a significantly weak association with biplane LAASVI (representing LA contractility) for both the study group (P < 0.0001, r = 0.72) and control group (P < 0.0001, r = 0.74).

Predictors of biplane left atrial active stroke volume index

Multivariate analysis was done to detect the strongest predictor for biplane LAASVI. Biplane LAV-pre was found to the strongest predictor rather than LAWV (P < 0.0001).

DISCUSSION

The importance of the LA lies in that it serves multiple functions; acting as a reservoir during LV systole; a conduit for blood flowing from the pulmonary veins to the LV during early diastole; a suction source that refills itself in early systole, and as an active contractile chamber that augments LV ventricular filling in late diastole that contributes up to 30% of total LV stroke volume in normal individuals. This atrial contribution is of particular importance in the setting of LV systolic dysfunction to maintain adequate LV stroke volume. There is growing evidence demonstrating that an enlarged LA is indicative of significant ventricular, atrial, or valvular disease, and acts as a marker of cardiovascular outcomes.[78]

This study was done to investigate the role of LAWV (represented by tissue Doppler imaging S-wave of the posterior wall of the LA) in active LA emptying (represented by LAASVI) in patients with ischemic heart disease and impaired LV systolic function.

Left atrial measurements

LA volume measurements are based on geometric assumptions (such as Simpson's method of discs and area/length methods), which although might not have not been thoroughly validated for the LA, several reports have shown them to correlate closely with the volumes measured using cine computed tomography or three-dimensional echocardiography. Thus, 2D echocardiography is used as a routine noninvasive method for measuring the LA volume.[910]

In this study, a statistically significant difference was found between study and control groups regarding LA volumes at the beginning of atrial systole (representing preload) (P < 0.0001). It was also demonstrated that a strong positive correlation exists between indexed biplane LA volume preatrial contraction and LAASVI that indicates that LAASVI is strongly influenced by preload.

This is in agreement with the results of the study done by Triposkiadis et al. who aimed to determine the LA ejection force and kinetic energy in patients with HF. They studied 58 HF patients (63.8% in NYHA II) and 48 controls; LA volumes were determined using the biplane area-length method while LA systolic function was assessed with the active emptying volume (ACTEV). It was shown that biplane LA volume at atrial systole was greater in the systolic HF group (P < 0.0001) indicating a greater preload in such patients.[11] Another study in 89 normal subjects, 38asymptomatic hypertensive patients, and 183 HF patients with preserved EF (HFPEF) defines as LVEF >45% found that those with HFPEF had larger LA dimensions compared with both (P < 0.0001). They concluded that the left atrium is frequently dilated in patients with HFPEF compared with controls despite similar EF and that LA dimensions showed powerful prognostic value independent of clinical variables. They concluded that despite decreased LA systolic shortening, overall LA systolic performance is augmented in chronic HF due to LA dilatation.[12] This is supported by the consensus that the relationship between LA size and cardiovascular disease burden and the outcome is stronger for indexed LAV than for LA dimension, area or diameter.[713]

In this study, we found that there was a statistically significant difference between both study and controls regarding LAASVI (P < 0.0001) confirming similar findings described by a study on 26 patients with ischemic dilated cardiomyopathy, 28 with idiopathic cardiomyopathy and 25 normal controls; where LA systolic function was assessed with the LA ACTEV. ACTEV was similar in both groups of cardiomyopathy patients, and both were greater than in the controls (P < 0.0001).[14]

We were also able to demonstrate that a negative correlation was present between LAWV and biplane LA volume preatrial contraction (P < 0.0001, r = −0.501) implying that increased preload in patients with impaired LV systolic function is associated with a reduction in active LA wall contractility.

In this study, multivariate analysis done for the factors affecting LAASVI showed that preload (represented by LA volume preatrial contraction) was the strongest predictor rather than LAWV.

The study by Yoshida et al. on 56 healthy controls and 30 patients with HF (14 with ischemia and 16 without ischemia) showed that LAWV was significantly lower in those with HF than in the controls in agreement with this study; however, on the contrary, their multivariate analysis performed revealed that LAWV is a more important factor than LA volume preatrial contraction in determining the LAASVI. They suggested that LA contractility is important for active LA emptying even when the LA and LV diastolic pressure is high.[15] The inclusion of nonischemic patients, their smaller sample size and also that their study was performed on Japanese individuals might explain the difference in findings compared to this study.

Study limitations

Limitations of the current study are that patients were from a single medical center with a relatively small number of subjects. Patients with nonischemic LV systolic dysfunction were not included. Patients with NYHA class IV symptoms were not included so the role of LA contractility in such patients and those with acute HF could not be demonstrated.

CONCLUSIONS

In ischemic heart disease patients with impaired LV systolic function, LA wall contractility (measured by LAWV) is reduced. However, LAASVI is increased as it is more affected by the LA dilatation caused by increased preload rather than LAWV.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.