The Role of the Left Atrial Strain Parameters on Grading of Aortic Regurgitation.

BACKGROUND: Grading the severity of aortic regurgitation (AR) is very important for clinical follow-up. In AR, left atrial (LA) mechanics can be affected in time and LA strain variations can be illuminating for the grading of AR. The purpose of this study is to determine whether the LA strain parameters are associated with the severity of AR or not.
METHODOLOGY: Sixty-four consecutive patients with AR were included in this study. Patients divided into three groups as mild (n: 22), moderate (n: 15), or severe (n: 27). All patients' LA strain measurements were performed and results were compared between groups.
RESULTS: Between the groups, LA reservoir (LA-Res) in the mild, moderate, and severe AR groups was 42.0 ± 18.0, 41.4 ± 14.8, and 29.2 ± 6.0, respectively (P: 0.002) and LA pump in the mild, moderate, and severe AR groups was 21.2 ± 8.7, 19.3 ± 7.4, and 13.1 ± 4.4, respectively (P < 0.001), different, while no difference was noticed on LA SRs, LA SRe, and LA SRa.
CONCLUSION: This study showed that LA-Res and LA pump parameters of the patients with severe AR significantly decreased compared to those of the mild and moderate AR group. The grading of the LA mechanics in patients with chronic AR might provide a supplementary contribution to the present parameters in the grading of AR. Copyright:

INTRODUCTION

Aortic regurgitation (AR) is a clinical status characterized by diastolic blood backflow from the aorta to the left ventricle (LV) due to the anomalies of valve cusps and aortic root and/or aortic annulus.[1] Severe chronic AR, by causing volume and pressure overload on LV, is likely to lead to left ventricular enlargement, a decrease in ejection fraction (EF), and processes resulting in death in the long term.

Echocardiography is the most significant diagnostic test in the assessment of valvular function.[2] Echocardiography allows for the examination of the anatomy of valve cusps and aortic root, the establishment of the diagnosis and severity of AR, and the assessment of the LV diameters and functions.[1]

Grading the severity of AR is very important for clinical follow-up and determining an optimal surgical date. Clinical and echocardiographic parameters are used for the grading of AR. In spite of numerous parameters, the severity of AR still remains unclear in some patients. New parameters that will be proposed with current improvements and tools in echocardiographic assessment might provide a supplementary contribution to the grading of AR.

The significance of the left atirum in cardiovascular performance has been recognized for a long time. In recent years, new visualization techniques that present a supplementary view for the assessment of the left atrium have been introduced. Atrial strain and strain rate analysis which are obtained by tissue Doppler imaging or two-dimensional speckle-tracking echocardiography (2D-STE) have been proved to be practical and repeatable for assessing the LA mechanics.[3] In AR, LA mechanics can be affected in time in parallel with the elevated LV end-diastolic pressure (LVEDP), and LA strain variations can be illuminating for the grading of AR.

The purpose of this study is to determine whether the LA strain parameters are associated with the severity of AR or not.

METHODOLOGY

Patient population

Our study was designed as a single-center, cross-sectional study, and consecutive AR patients who applied to the echocardiography laboratory of our hospital within 4 months were examined. Following the ethics approval of the local ethics committee, the consent of the patients who were included in the study was obtained. Ninety-one patients were examined in our study.

Sixty-four patients were included in our study after using exclusion criteria [Figure 1]. Patients divided according to the AR degree into three groups as mild (n: 22)-moderate (n: 15), or severe (n: 27). All of the patients who met both exclusion and inclusion criteria were consecutively included in the study.

Figure 1

Flow diagram of study patients

Exclusion criteria

Patients with acute AR or decompensated valvular failure

Other concomitant valvular diseases of more than mild in severity

Known ischemic heart disease

Previous cardiac or valve surgery

Reduced LVEF (≤50%), and diastolic dysfunction (E/e' >10)

Inadequate echocardiographic image quality for 2D-STE analysis was excluded.

Clinical characteristics

All patients included in the study were subjected to a complete physical examination. Following the measurement of height and weight anthropometrically, body surface area (m2) and body mass index (kg/m2) were calculated for each patient. After resting in a quiet room for 10 min, the blood pressures of the patients were measured.

The most common cardiovascular risk factors seen in our study population were hypertension and smoking in parallel with population-based studies.[4] In the advanced AR group, five of our patients were classified as New York Heart Association (NYHA) Class 1, and three of our patients were classified as NYHA Class 2 Other patients were asymptomatic.

Echocardiography

Transthoracic echocardiographic images were obtained using an ultrasound system, Vivid-7 (General Electric Vingmed), from the patients in the left lateral decubitus position, and these images were digitally kept for offline examination (EchoPAC version 110.0.0, GE-Vingmed). Echocardiographic acquisitions (colored, standard 2D, pulsed, and continuous-wave Doppler) were done. Standard M-mode images at a parasternal long-axis view were used to obtain the LV dimensions. Then, LV end-diastolic and end-systolic volumes were calculated using biplane Simpson's method from the apical views (two and four chamber). Following the aforementioned measurements, LVEF was calculated and the results were expressed with percentage. The biplane area–length method was used for the measurement of the LA volume.[5]

All measurements and evaluations performed in the study were carried out considering the guidelines of the European Society of Echocardiography. Detailed examination of the aortic root, AV, and proximal ascending aorta was performed taking into account the standard guidelines. To evaluate the AR severity, comprehensive, color, continuous, and pulsed-wave Doppler recordings were carried out considering the recommendations that included the measurement of regurgitant jet width, vena contracta (VC) width, pressure half-time, and diastolic flow reversal in the descending aorta.[678]

AR severity was identified by integrating information from semi-quantitative parameters based on published guidelines, (AR jet density, AR jet area in the LV outflow tract, the AR jet width of the LV outflow tract, diastolic flow reversal in the descending aorta, and AR PHT).[67]

AR severity was fixed on by two expert cardiologists who were working in the echocardiography laboratory with more than 5 years of experience. They used semi-quantitative echocardiographic methods for deciding severity degree if both of them were in the same decision on the severity degree of the patients in the study.

Left atrial strain parameters

2D grayscale images of three cardiac cycles from apical four-chamber views were obtained with the help of conventional ultrasound, with a frame rate of 60–90 frames/s. The lateral and septal walls of the LA were continuously imaged without important dropouts. Two experienced cardiologists who were blinded to the study groups carried out the examinations. To calculate the strain rate and the LA strain, the off-line EchoPAc workstation was used by the researchers. As a reference point, the LA 2D-STE curves were acquired using the R-wave onset of the electrocardiogram. Following the manual definition of the endocardial border, the software automatically developed the tracing for each view. When the automatically acquired tracking segments were sufficient for the analysis, the researchers allowed the software to read the data. For insufficient tracking segments, manual adjusting or software parameters changing were performed.

Global LA strain and strain rate parameters were evaluated. QRS-onset speckle-tracking echocardiography analysis for LA: LA peak strain prior to mitral valve opening was taken as LA reservoir (LA-Res), and LA strain prior to atrial contraction (onset of the P-wave on electrocardiography) was taken as LA pump [Figure 2]. LA strain rate throughout ventricular systole (LA-SRs), LA-SRe throughout ventricular passive filling, and LA-SRa throughout active atrial contraction were measured as LA function parameters.

Figure 2

Left atrial strain parameters. QRS-onset speckle-tracking echocardiography analysis for LA, LA reservoir: LA peak strain during just before mitral valve opening, LA pump: Just before atrial contraction during left atrial late diastole (onset of the P-wave on electrocardiography)

Statistical analysis

All statistical analyses were carried out using SPSS 22.0 for Windows (IBM, New York, USA). Descriptive statistics for numerical variables were expressed as mean ± standard deviation, while categorical data were reported as numerical values and percentages. The Chi-square test and Fisher's exact Chi-square test were used to compare categorical variables between the groups. One-way anova test was used to compare means between groups. The statistical significance was set at P < 0.05, and the confidence interval at 95%.

RESULTS

In our study, we researched the role of the LA strain parameters on the grading of AR. According to the grading, the patients were divided into three groups: mild, moderate, and severe AR. The basal variables among these groups are presented in Table 1. Except for gender and age, no statistically significant difference was noticed on other parameters among the groups.

Table 1

Demographic features of mild/moderate and severe aortic regurgitation patients

	Mild (n=22), n (%)	Moderate (n=15), n (%)	Severe (n=27), n (%)	P
Age (years)	53.6±15.7	48.5±19.6	42.1±19.3	0.105
Gender male	10 (45.5)	8 (53.3)	20 (74.1)	0.04
DM	4 (18)	2 (13)	5 (18)	>0.05
HT	6 (27)	4 (26)	8 (29.6)	>0.05
Smoking	8 (36)	6 (40)	10 (37)	>0.05
DL	4 (18)	3 (20)	5 (18)	>0.05

DM=Diabetes mellitus, HT=Hypertension, DL=Dyslipidemia

Echocardiographic parameters are defined in Table 2. According to these parameters, end-diastolic volume (EDV) was detected to be 103.7 ± 35.7 mL in the mild AR group, 119.0 ± 40.2 mL in the moderate AR group, and 167.0 ± 59.7 mL in the severe AR group (P < 0.001). End-systolic volume (ESV) was detected to be 39.1 ± 16.6 in the mild AR group, 46 ± 20.4 mL in the moderate AR group, and 65.9 ± 27.4 mL in the severe AR group (P < 0.001). AR VC was detected to be 0.3 ± 0.1 cm in the mild AR group, 0.4 ± 0.1 cm in the moderate AR group, and 0.7 ± 0.1 cm (P < 0.001) in the severe AR group. Left atrium volume (LAV) was detected to be 46.7 ± 9.1 mL in the mild AR group, 46.5 ± 10.1 mL in the moderate AR group, and 59.5 ± 10.7 mL in the severe AR group with a P = 0.005.

Table 2

Echocardiographic features of mild/moderate and severe aortic regurgitation patients

Echocardiographic findings	Mild (n=22)	Moderate (n=15)	Severe (n=27)	P
Aortic diameter (cm)	3.4±0.6	3.5±0.5	3.6±0.6	0.47
EDV (mL)	103.7±35.7	119.0±40.2	167.0±59.7	<0.001
ESV (mL)	39.1±16.6	46±20.4	65.9±27.4	<0.001
LVEF (%)	62.5±6.3	61.3±8.6	60.8±9.6	0.77
E (cm/s)	0.5±0.1	0.6±0.2	0.5±0.1	0.89
A (cm/s)	0.6±0.1	0.6±0.1	0.6±0.1	0.51
MAPSE (cm/s)	1.5±0.3	1.5±0.3	1.5±0.3	0.88
AR VC (cm)	0.3±0.1	0.4±0.1	0.7±0.1	<0.001
LAV (mL)	46.7±9.1	46.5±10.1	59.5±10.7	0.005
AR PHT (ms)	480.0±102.3	444.8±105.78	243.2±70.0	<0.001

EDV=End diastolic volume, ESV=End systolic volume, LAV=Left atrial volume, AR=Aortic regurgitation, PHT=Pressure half time, VC=Vena contracta, LVEF=Left ventricular ejection fraction, MAPSE=Mitral annular plane systolic excursion

In Table 3, left atrial mechanics are listed, and between the groups; reservoir (42.0 ± 18.0 in the mild AR group, 41.4 ± 14.8 in the moderate AR group, and 29.2 ± 6.0 in the severe AR group with a P value of 0.002) and pump (21.2 ± 8.7 in the mild AR group, 19.3 ± 7.4 in the moderate AR group, and 13.1 ± 4.4 in the severe AR group (P < 0.001)), statistically significant difference was noticed, while no statistically significant difference was noticed on LA SRs, LASRe, and LA SRa.

Table 3

Left atrial strain and strain rate features of mild/moderate and severe aortic regurgitation patients

	Mild (n=22)	Moderate (n=15)	Severe (n=27)	P
LA reservoir	42.0±18.0	41.4±14.8	29.2±6.0	0.002
LA pump	21.2±8.7	19.3±7.4	13.1±4.4	<0.001
LA SRs	2.0±0.8	2.0±0.6	2.0±0.6	0.97
LA SRe	−1.7±0.8	−1.5±0.8	−1.7±0.8	0.74
LA SRa	−2.5±1.2	−2.4±0.9	−1.9±1.3	0.24

LA=Left atrial, LA-reservoir=Peak left atrial strain during ventricular systole, LA-pump=Peak left atrial strain during late diastole, LA-SRs=Peak left atrial strain rate during ventricular systole, LA-Sre=Peak left atrial strain rate during early diastole, LA-Sra=Peak left atrial strain rate during atrial systole

With the post hoc Tukey analysis on the grading of AR, the P value of mild and moderate AR for the LA-Res was determined to be 0.98, while the P value of mild and severe AR was determined to be 0.004, and the P value of moderate and severe AR was determined to be 0.02. The P value of mild and moderate AR for LA pump was determined to be 0.69, while mild-to-severe AR was determined to be P < 0.001, and the P value of moderate-to-severe AR was determined to be 0.02.

For EDV, the P value of mild-to-moderate AR was determined to be 0.62, whereas mild-to-severe AR was determined to be P < 0.001, and the P value of moderate-to-severe AR was determined to be 0.01. For ESV, the P value of mild-to-moderate AR was determined to be 0.58, whereas mild-to-severe AR was determined to be P < 0.001, and the P value of moderate-to-severe AR was determined to be 0.03. For AR VC, the P value of mild to moderate AR was determined to be 0,01, while mild-to-severe AR was determined to be P < 0.001 and moderate-to-severe AR was determined to be P < 0.001. For LAV, the P value of mild-to-moderate AR was determined to be 0.99, while the P value of mild-to-severe AR was determined to be 0.01 and moderate-to-severe AR was determined to be 0.02.

DISCUSSION

In our study, basically, the facts that

LA mechanics were disrupted in AR patients

LA-Res and LA pump decreased as the severity of AR increased

LA-Res and LA pump significantly decreased in severe AR compared to mild and moderate AR were determined.

In our study, we show that LA-Res and LA pump significantly decreased in severe AR compared to mild and moderate AR and LA-Res and LA pump decreased as the severity of AR increased.

The grading of AR for the patient's follow-up and planning the treatment after the diagnosis of AR is critical. Patients with normal levels of LV diameters and functions and who are asymptomatic with mild and moderate AR do not need to be treated, and a 12-to-24-month echocardiographic follow-up period is suggested for them. On the other hand, patients with normal LV functions and who are asymptomatic with severe AR are supposed to be examined at a 6-month period.[9]

The grading of AR needs to be done with many clinical and echocardiographic parameters, without separating them. Some of the echocardiographic parameters are EROA, regurgitant volume, Jet/left ventricular outflow tract ratio, VC, holodiastolic flow reversal, LV dilatation, and AR PHT. Despite all of these parameters that are in use for the grading of AR, an ultimate decision cannot be taken in some cases and the severity of AR cannot be clarified. Each decrease in one unit of LA strain of reservoir phase was demonstrated to increase the likelihood of the progress of pulmonary HT in AR patients by 6%.[10] These data show the importance of the LA mechanics in chronic AR. In our study, it was noticed that LA-Res and LA pump significantly decreased in severe AR patients compared to the patients with mild and moderate AR, and that LA strain parameters might contribute to the grading of AR.

Some of the parameters used for the grading of AR, and especially AR PHT value, were associated with elevated LVEDP, and they were inversely correlated. In other words, as LVEDP increases, AR PHT value decreases, and the values below 200 ms are interpreted to be related to severe AR. Elevated LVEDP present in AR is closely related to the LA mechanics, and decreased LA strain is an independent predictor of elevated LVEDP.[11] LA dimension might be considered to be an approximate indicator of LV diastolic filling pressures.[12]

In healthy individuals, the left atrium is quite flexible in exposure to rather low pressures; however, it becomes tense and stiff in case of acute and chronic damage.[131415] The left atrium is directly exposed to LV vacuum pressure during diastole; therefore, in the absence of LA volume overload, an enlarged left atrium is a strong indicator of elevated LV filling pressure, which also explains the causality between LA dilatation and negative outcome in patient with acute myocardial infarction.[12]

LA-Res is significantly associated with systolic performance measurements such as EF and LV systolic volume index. In other words, both diastolic (LVEDP) and systolic (LV systolic volume index) LV variables are independent predictors of the LA-Res.[16] Besides, the LA-Res presents more precise information than the LA volume index and other Doppler dependent variables for the assessment of LVEDP.

Severe chronic AR causes pressure and volume overload on the left ventricle. According to LaPlace's law, wall stress is about the division of wall thickness by intraventricular pressure and the radius. LV dilatation increases LV systolic wall stress, which is required for obtaining the systolic pressure level similar to the one obtained at normal ventricular diameter. Therefore, in chronic AR, both preload and afterload increase simultaneously. LV systolic function is preserved with LV dilatation and hypertrophy. The amount of regurgitant volume is directly associated with volume overload, and it is directly proportional with the severity of the leak. While mild AR causes volume overload minimally, severe AR might result in progressive circles dilatation due to massive volume overload.[1]

Extreme volume overload in AR causes the dysfunction of the myocardial mechanics insidiously.[17] In compensated severe AR, extreme volume overload is adjusted by eccentric hypertrophy, which includes lengthened myofibrils.[1819] In spite of elevated regurgitant volume, diastolic adaptation is preserved by keeping the LV filling pressures at normal or mildly elevated levels with eccentric hypertrophy. Meanwhile, EF is maintained at normal levels by balancing increased volume overload with increased LV bulk.[20] Even though it was compensated, in mild and moderate AR, it was demonstrated that global LV performance significantly decreased despite normal EF values.[21] Thus, in order an optimal surgical date to be determined, new indicators that would show subclinical dysfunction are required.[17]

In decompensated AR, decompensation progresses due to increased interstitial fibrosis and decreased compliance and pressure and volume increase after LV systole. LV diastolic compliance decreases due to hypertrophy and fibrosis, and it coexists with systolic function. This condition causes high filling pressures and symptoms of heart failure.

'At the stages of decompensation, LA and pulmonary capillary wedge pressure increase,' and cardiac output begins to decrease firstly during exercise, then during rest. Increased LA pressure is directly associated with regurgitant volume, and it can be stated that this association is continuous. Hence, in parallel with the facts we obtained with the LA mechanics, it can be suggested that LA strain parameters might contribute to the grading of AR.

When the pathophysiology of chronic AR is considered, it is not surprising that LVEDP and LA strain parameters, which increase with the severity of AR, are affected. In our study, it was demonstrated that among the patients whose diseases were classified as mild, moderate, and severe AR, LA-Res and LA pump P valuesof the severe AR group significantly decreased compared to those of the mild and moderate group. The decrease was not significant for the difference between mild and moderate. It is possible that LV compensatory capacity is not sufficient due to severe LV overload, and as LVEDP increases, it causes the LA mechanics and strain parameters to be affected in time. When considered from this point of view, LA strain parameters can provide a supplementary contribution to and be illuminating for echo parameters, which have been clinical and in use for the grading of AR for a long time.

The fact that our study was monocentric, observational and the number of the patients was not sufficient. LVEDP could not be calculated with invasive methods and AR degree was calculated by semi quantitative methods are some of the limitations of our study. However,a group of patients whom could only be rarely encountered in clinical practice like isolated AR were chosen. The likelihood that a routinely-performed invasive procedure would increase the complication risk in the present group of patients and some ethical issues led to these limitations.Polycentric studies that can be carried out with a larger group of patients can help us to obtain more precise facts on this issue.

CONCLUSION

In our study, it was detected that the LA-Res and LA pump parameters of the patients with severe AR significantly decreased compared to those of the mild and moderate AR group. The grading of the LA mechanics in patients with chronic AR might provide a supplementary contribution to the present parameters with a holistic approach in the grading of AR.

Ethical clearance

22.09.2020/3.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.