Left atrial mechanics in postmenopausal hypertensive women with leftventricle diastolic dysfunction

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Left atrial mechanics in postmenopausal hypertensive women with leftventricle diastolic dysfunction

Kolesnyk Mykhaylo

MD, PhD, DSci, Professor of Department of Family Medicine, Therapy, Cardiology and Neurology, Faculty of Postgraduate Education,

Zaporizhzhia State Medical University

Sokolova Maryna

MD, Post-Graduate Student of Department of Family Medicine, Therapy, Cardiology and Neurology, Faculty of Postgraduate Education, Zaporizhzhia State Medical University



Abstract

Background and Objectives: Evaluation of diastolic function (DF) of left ventricle (LV) provides an important prognostic information in many cardiovascular diseases. The existing algorithms for its diagnosis do not always permit to identify its deterioration. The aim of our study was to assess the longitudinal strain of the left atrium (LA) in postmenopausal women with arterial hypertension (AH) and different variants of DF; Materials and Methods: The study involved 100 postmenopausal hypertensive women (mean age - 57.8 ± 4.3 years). All patients underwent general clinical examination, standard transthoracic and speckle tracking echocardiography. Diagnostics of diastolic dysfunction (DD) of the LV was performed in accordance with the 2009 year recommendations of the American and European society of echocardiography. All patients were divided into three groups depending on the state of DF LV: the 1^st group included 31 women with normal DF LV, the 2^nd group consisted of 38 patients with indetermined result, and 31 individuals of the 3^rd group had LV DD. Results: Women with DD LV had higher values of LAVI and LV mass index. Abnormal values of e' sept, e' lat and E/e' were found in patients with indetermined DF and with DD. Impairment of the reservoir phase of LA function was associated with the presence of DD LV. Subjects with any LV DF except normal had lower values of LA deformation (p<0,05). Reduction of LA GLS in women with AH and abnormal DF LV was detected only with the use of R- synchronization of ECG. E/e'/GLS LA was increased as far as breaking DF LV with its maximum value in women with DD LV. Conclusion: Left atrial strain can be used to assess left ventricular diastolic function and differentiate its normal state and varying degrees of diastolic dysfunction in postmenopausal women with AH.

Keywords: diastolic dysfunction, arterial hypertension, postmenopausal women, speckle tracking echocardiography, left atrium strain



Introduction

Cardiovascular diseases are the leading cause of morbidity and mortality in industrialised societies [1]. So, there is an urgent need for early detection of structural and functional heart abnormalities before coronary events or heart failure (HF) developement. Arterial hypertension (AH) is the most common risk factor for HF in general population. HF is more prevalent in women than in men in all age groups [2]. diastolic dysfunction arterial hypertension

Diastolic dysfunction (DD) of the left ventricle (LV) is one of the cornerstone mechanisms of HF symptoms manifestation [3]. A large amount of postmenopausal women showed that AH causes primarily HF with preserved ejection fraction (HFpEF) [4]. Detection of LV DD is especially important in patients with preserved ejection fraction, as it allows to establish the mechanism of chronic heart failure. Echocardiography is the main non-invasive method for evaluating of LV diastolic function. Cooperative recommendations of the American and European Society of Echocardiography for the evaluation of LV diastolic function suggest an algorithm for both identifying and assessing the severity LV DD [5]. However, in many patients (according to some data up to 48%) it is not possible to diagnose and classify LV DD using this guidelines [6].

Considering that the principal role of the left atrium (LA) is to modulate left ventricular filling, it was proposed to determine the longitudinal deformation of the LA by speckle tracking echocardiography [7]. There is limited data describing the changes in LA strain in patient with different degrees of LV DD [8]. So, LA strain measurement may be reliable and simple noninvasive tool to provide additional information about DF state in patients with inconclusive results by standard algorithm.

The purpose of our study was to assess the longitudinal deformation (strain) of the left atrium in postmenopausal women with arterial hypertension and different variants of diastolic function.



1. Materials and methods

The study involved 100 post-menopausal hypertensive women (mean age - 57.8 ± 4.3 years), admitted to the cardiological department of University Clinic of Zaporizhzhia State Medical University. Diagnosis of AH was established in accordance with the recommendations of the Ukrainian Association of Cardiologists and the European Society of Cardiology for the management of arterial hypertension [9; 10]. All patients underwent ambulatory blood pressure monitoring using the ABPM-04 device (Meditech, Hungary). Postmenopausal period was defined as at least 12 months of amenorrhea and serum FSH above 30 mIU / ml [11]. The exclusion criteria were secondary hypertension, diabetes, history of coronary artery disease, manifestation of heart failure, moderate or severe valvular disease, atrial fibrillation, conduction disorders, oncological diseases, chronic diseases of the lungs, the use of hormone replacement therapy as well. All patients gave informed written consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, the design of the study was agreed with the local ethics committee.

After clinical examination all patients underwent a standard transthoracic and speckle tracking echocardiography using Vivid E9 XDClear (General Electric, USA) ultrasound system. Left ventricular end-diastolic (LV-EDD) and end-systolic diameters (LV-ESD), LA maximum anterior-posterior (A-P) diameter, thickness of the interventricular septum (IVS) and thickness of the LV posterior wall (LVPW) were measured from the internal dimensions obtained from parasternal long axis view in B-mode. LV mass was calculated by the American Society of Echocardiography formula and then indexed to body surface area (BSA). LV mass in grams was calculated from B-mode echocardiograms according to the formula [12]:

LV mass = 0.8 x (1.04 x [{LV-

EDD'+LVPW+IVS}³-{LV-EDD}³]>+0.6;

LV hypertrophy was defined as a LV mass index more than 95 g/m².

Relative wall thickness (RWT) was calculated according to the formula:

RWT = (2 * LVPW)/LV-EDD.

LV ejection fraction was measured using the modified biplane Simpson's rule. LA area and volume were measured using the biplane method of disks (modified Simpson's rule), in the apical 4- and 2-chamber view on the frame before mitral valves opening. LA volume was indexed to BSA. LAVI was used to estimate LA dilation with cut-off value 34 ml/m² [13].

Pulsed spectral Doppler echocardiography was performed using a 5-mm sample volume placed at the tips of the mitral leaflets as parallel as possible to inflow. Tissue Doppler measurements were sampled at the level of the mitral annulus over the septal (e' sept) and lateral (e' lat) wall. The ratio of the transmitral Doppler E wave velocity and the composite mean of e' were then used to calculate the E/e' ratio. All parameters were measured three times and then averaged.

Diagnostics of diastolic dysfunction of the LV and its gradation in all patients was performed in accordance with the 2009 year recommendations of the American and European society of echocardiography. [14]. The LV diastolic function was considered normal when e' sept > 8 cm/s, e' lat > 10 cm/s and LAVI < 34 ml/m². If two of these three parameters were violated, an inde- termined result of LV DF was diagnosed. LV DD was registered in those patients who had the following parameters: e' sept <8 cm/s, e' lat < 10 cm/s and LAVI > 34 ml/m².

Speckle tracking echocardiography. Apical four- and two-chamber views images were obtained during breath hold with ECG synchronization. One of three standard leads (I, II or III) was chosen to get stable ECG trace with clear P- and R-wave. Particular attention was given to obtain non-foreshortened LA view with clear delineation of myocardial tissue. The frame rate was set between 60 and 80 per second. The three cardiac cycles were recorded and averaged. All images and cineloops were stored for off-line analysis on Echopac (version 113) using software package 2D Strain. First, the atrial endocardial border was traced by a point-and-click method. Then, LA wall was divided into six segments in every view by automatic creation of a region of interest (ROI). After manual adjustment of ROI width and shape the tracking quality for each segment was automatically analysed. Segments with inadequately tracking were removed from further analysis. Finally, the software generates strain curves for each atrial segment. Strain was defined as the percentage change in object's dimension in comparison to its initial dimension.

The analysis was performed using two variants of ECG-triggering:

1) Onset of P wave as reference point (Fig. 1) The strain curve has biphasic view with first negative part reflecting LA contraction (LA LScont) and second positive part which mirrors conduit function (LA LScond). The sum of these peaks equals reservoir (total) strain (LA LStot). LA LScont, LA LScond and their summation LStot values were obtained by averaging individual values from 12 LA segments. Global longitudinal strain (GLS) LA was calculated by averaging values observed in all LA segments, and by separately averaging values measured in 4- and 2-chamber views (4- and 2-chamber average GLS)

Fig. 1. The normal graph of LA longitudinal deformation by P-wave triggering method of analysis. Scont - strain in the contractile phase; Sres - strain in the reservoir phase; Sgl - global strain.

Analysis of the reproducibility of myocardial strain was performed in our previous study [15].

To achieve the purpose of the study, all postmenopausal women with AH were divided into three groups depending on the state of LV diastolic function: the 1^st group included 31 women with normal LV DF, the 2nd group consist of 38 patients with indetermined result, and 31 individuals of the 3rd group had LV DD. Among patients of last group 2 women had LV DD of the 1st grade, 22 one's with 2nd grade LV DD and 7 patients had LV DD of 3rd grade.

2) R -wave as initial point of analysis (Fig. 1) All strain values are positive, and there are two peaks that correspond to reservoir function (first peak between R wave and T wave) and atrial contractile function (starting on the P wave). We measured the first peak only which equals GLS LA.

Fig. 2. The normal graph of LA longitudinal strain by R-wave triggering method of analysis.

Statistics. The distribution of variables was tested by Shapiro-Wilk test. Continuous variables were presented as “mean + standard deviation” or as “median and interquartile range” when data was non-parametric. Categorical variables were presented as absolute values and percentages. Differences between two independent groups were evaluated using Mann-Whitney test. Krus- kal-Wallis analysis was performed to compare three independent groups and differences between pairs of groups were assessed by post hoc Mann-Whitney criterion. A P value < 0.05 was considered statistically significant. All statistical analyses were performed using Statistica13.0(StatSoftInk., №JPZ8041382130ARCN10-J, USA).

Table 1.

Clinical characteristics and standard echocardiography data of the patients.

Parameter	Patients with AH and normal LV DF (N=31)	Patients with AH and indetermined LV DF (N=38)	Patients with AH and LV DD (N=31)	P
Age, years	56 (53;60)	56 (55;60)	60 (57;62)*%	p =,0034
AH duration, years	8 (4; 18)	7,5 (5;10)	11 (7;19)%	p =,05
Menopause duration, years	8 (5; 11)	7,5 (3;14)	9 (7;13)	p =,4923
24-hour SBP, mm Hg	127 (117; 138)	132 (121; 142)	130 (118;146)	p =,2177
24-hour DBP, mm Hg	73,5 (69;80)	76 (72;85)	76 (68;82)	p =,3175
LV-EDD, cm	4,23 (4,13;4,59)	4,3 (4,13;4,55)	4,52 (4,1;4,76)	p =,5805
LV-ESD, cm	2,7 (2,38;2,94)	2,69 (2,5;2,96)	2,77 (2,56;2,95)	p =,6116
IVS, cm	1,14 (0,94;1,2)	1,17 (1,01;1,26)*	1,21 (1,08;1,32)*	p =,0159
LVPW, cm	0,96 (0,85;1,07)	1,04 (0,94;1,07)*	1,08 (0,94;1,16)*	p =,0092
LV mass index, g/m2	81 (74;92)	89,5 (79;100)*	99 (87;113)*%	p =,0006
EF LV, %	66 (61;70)	66,5 (62;71)	66 (62;72)	p =,7869
LA volume index, ml/ m2	32,94 (28,8;38)	31,4 (26,4;33,3)	37,2 (35,1; 40,3)*%	р<0,0001
e' sept, m/s	8,6 (8;9,1)	6,3 (5,7;7,0)*	6,7 (5,88;7,43)*	P<0,0001
e' lat, m/s	11 ( 10,1 ;11,7)	7,75 (6,6;9,8)*	7,7 (6,6; 8,8)*	P<0,0001
E/e'	8,07 (7,36;9,6)	9,91 (8,44;11,6)*	11 (9,92; 13,03)*%	P<0,0001

* significant differences in comparison with patients with AH and normal LV DF № significant differences in comparison with patients with AH and indetermined LV DF



2. Results

The clinical characteristics and standard echocardiography data of the patients are presented in Table 1. Study participants were comparable for the duration of AH and menopause. Women with DD LV were older than the patients of the other two groups. No differences between groups in diastolic or systolic blood pressure were found. The 24 hour blood pressure monitoring was performed under the similar antihypertensive treatment.

In the present study, thickness of IVS and LVPW were significantly higher among the women of the 3^rd group than amongst patients with normal and even in- determined DF LV. Women with DD LV had also higher values of LAVI and LV mass index, but there were not any significant difference in either end-systolic nor end-diastolic LV diameters.

Table 2

LA strain in postmenopausal patients with arterial hypertension and different states of DF LV.

Parameter	Patients with AH and normal LV DF (N=31)	Patients with AH and indetermined LV DF (N=38)	Patients with AH and LV DD (N=31)	P
P- triggering
LS LA in reservoir phase (2- chamber view), %	16,43913,66; 20,26)	11,16(8,39; 15,54)*	12,38(8,98; 14,2)*	p =,0004
LS LA in reservoir phase (4- chamber view), %	16,01 (14,18; 20,08)	11,72 (8,68; 14,95)*	12,2 (10,44; 19,84)*	p =,0003
LS LA in reservoir phase (по 2м пози-ціям), %	16,08 (13,68; 18,8)	11,95 (8,68; 14,65)*	12,53 (10; 16,19)*	p =,0001
LS LA in contraction phase (2- chamber view), %	-14,06 (-19,2; -11,47)	-16,41 (-18,32; -14,24)	-14,84 (-17,55; - 12,49)	p =,1230
LS LA in contraction phase (4- chamber view), %	-15,14 (-17,23; -12,35)	-15,45 (-17,76;-13,34)	-14,14 (-16,15; - 11,9)	p =,3836

Our study showed worse values of e' sept, e' lat and E/e' in patients with indetermined DF and with DD LV compared to women without violation of DF LV. But only E/e' made it possible to identify the differences between participants of the 2nd and the 3rd groups.

Evaluation of LA strain in postmenopausal women with AH (Table 2) demonstrated impairment of the reservoir phases of LA function associated with the presence of LV DD. Subjects with any LV DF except normal had lower values of LA deformation, when compared with normal subjects (p<0,05). The values of longitudinal strain of LA in the reservoir phase were lower as for each position separately (2- and 4- chambers), and for two positions in general. Of interest, absolute LA strain meaning in patients with indetermined DF LV was more lower than in DD LV group, though not statistically significant (p>0,05). In the same time, there were not found any significant differences in the contraction phase LA function between groups. Preserving the contractile function of LA in patients with AH may indicate an increase in the involvement of LA in diastolic filling.

Reduction of LA GLS in women with AH and abnormal DF LV compared with patients of 1st group was detected only with the use of R-synchronization of ECG, that considered as more universal. Notably, absolute values of GLS LA gradually decrease from the highest values in patients with normal DF LV to lowest ones in DD LV patients. In this way, meanings of GLS LA in patients with indetermined result of DF LV represent an intermediate stage from normal DF to DD LV.

LS LA in contraction phase (average of both chambers), %	-14,91 (-17,64; -12,76)	-15,94 (-17,54; -14,46)	-14,85 (-16,86; - 12,11)	p =,1293
GLS LA (2- chamber view), %	28,22 (22,8; 33,89)	26,64 (24,58; 30,77)	26,19 (21,48; 28,38)	p =,2245
GLS LA (4- chamber view), %	30,28 (25,99; 33,26)	26,4 (23,22; 29,48)*	26,04 (21,74; 30,59)	p =,0642
GLS LA (average of both chambers), %	30,05 (25,26; 33,86	26,04 (24,29; 29,37)*	26,46 (23,15; 31,06)	p =,0778
R- triggering
GLS LA (2-chamber view), %	35,71 (29,93; 41,56)	29,55 (25,68; 36,38)*	30,15 (23,29; 35,17)*	p =,0089
GLS LA (4-chamber view), %	33,5 (26,13; 40,27)	31,06(26,92; 35,32)	28,99(24,49; 35,71)	p =,2768
GLS LA (average of both chambers), %	34,8(30,2; 39,9)	30,78(26,46; 34,88)*	28,91(24,22; 35,99)*	p =,0277
E/e' / GLS LA	0,24 (0,18; 0,31)	0,32 (0,27; 0,39)*	0,37 (0,31; 0,46)*	p<0,0001

* significant differences in comparison with patients with AH and normal LVDF № significant differences in comparison with patients with AH and indetermined LV DF

Diastolic dysfunction is unquestionably linked to increased myocardial stiffness. The ratio E/e' / GLS LA is used for indirectly evaluate of it. In our research indicator E/e'/ GLS LA was increased as far as breaking DF LV with its maximum value in women with DD LV.



Discussion

In our study, the relationship between the state of LV diastolic function and the left atrial strain indices in postmenopausal women with arterial hypertension was shown. Diastolic dysfunction of the left ventricle has important prognostic significance in cardiovascular diseases, even in the absence of expressed structural changes in the heart. It has been reported earlier that the frequency diastolic impairment due to changing arterial elastance increases with age and is higher in women than in men [16; 17]. It has previously been registered that LV diastolic dysfunction does not negatively affect clinical parameters when it is not associated with changes in the index of left cardiac structural remodelling, based on LV hypertrophy magnitude and atrial dilation [18]. Simultaneously, LV abnormalities, such as LV hypertrophy and LV walls contraction disturbance, make the substrate for LV diastolic dysfunction and are common in patients with diastolic HF [14]. Increased LA volume is an independent predictor of HF and worsened mortality in previously asymptomatic subjects with a preserved EF [19].

Systolic and diastolic function do not seem to improve the ability of LV mass in predicting cardiovascular risk, and they did not improve it significantly in hypertensives [20], nevertheless, doppler transmitral inflow pattern has been tested successfully in of prognosis in hypertensive patients in large epidemiologic studies [21; 22]. Tissue Doppler indices predicted risk of mortality independent of age and gender [23; 24]. However, increasing of only E/e' in patients with preserved EF can not be perfectly accurate [25]. That's why it becomes obvious that multiple echocar- diographic parameters are required for accurate assessment of DD LV.

According to literary data, GLS is a powerful predictor of cardiac events and a better prognostic parameter than EF in heart failure [26]. Also described alterations in LA strain with some cardiovascular diseases and conditions [27; 28]. But some researchers found out that LA strain in the contraction phase in hypertensive patients may even increase, especially in the presence of LV hypertrophy [29]. Other recent studies have drawn attention to the presence of a higher LV mass and LA volume as well as a lower LA contractile reserve in patients with diastolic HF [30; 31]. Besides, previously it was shown that decreased contribution of active LA emptying to ventricular filling during diastole was strongly predictive of adverse cardiac events and death [32].

Speckle-tracking echocardiography is a promising diagnostic tool for detailed LA function evaluation [33]. This technique was successfully tested in various pathological conditions [34; 35]. However, the methodology of LA strain analysis needs standardization. The choice of zero reference point (P- or R-wave on ECG) for building LA deformation curves is still under discussion. The use of R- variant LA deformation analysis is considered to be a priority in the consensus document of the European Association for Cardiovascular Imaging because of its versatility and possibility to use it in case of cardiac arrhythmias, in particular an atrial fibrillation [35].

An important point in the evaluation of LV DF is estimating of LA stiffness. The ratio of invasively measured pulmonary capillary wedge pressure to LA deformation was used for this [37]. The E/e' ratio was also proposed for using in conjunction with LA strain to derive a noninvasive dimensionless parameter [28; 38]. The use of three-dimensional йchocardiographie technologies as well as their combination with assessing LA deformation are a promising direction in the evaluation of diastolic function [39].

The main limitation of our study is the absence of a verifying method for assessing the state of DF LV, inasmuch as invasive procedures have not been conducted in the individuals we examined. In future studies it is necessary to search criteria for assessing left ventricular diastolic function, including the use of left atrial strain, to minimize the number of indetermined results.



Conclusions

Left atrial strain can be used to assess left ventricular diastolic function and differentiate its normal state and varying degrees of diastolic dysfunction in postmenopausal women with arterial hypertension.

Conflicts of Interest

The authors state no conflict of interest.



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