Correlation of Left Atrial Strain with Invasively Measured Left Ventricular End-Diastolic Pressure; determining LA strain cut-off value

doi:10.21203/rs.3.rs-2194466/v1

Purpose Left atrium (LA) longitudinal strain with speckle tracking has been proposed as a non-invasive method for the assessment of left ventricular filling pressure and diastolic dysfunction. This study aimed to investigate left atrial strain (LAS) compared to invasively measured left ventricular filling pressure. Methods All Patients candidates for coronary angiography were consecutively recruited. Longitudinal LA strain measured by Transthoracic echocardiography. Left ventricular end-diastolic pressure (LVEDP) pressure was invasively measured. Current echocardiographic modalities for diastolic function evaluated. Results A total of 125 people were included. 45 patients had preserved ejection fraction (EF ≥ 50%) and 85 patients had reduced EF (EF < 50%) and compared two groups. LVEDP was significantly higher in reduced EF compared to preserved EF (P-value<0.001). LA-reservoir and LA-booster strains were significantly lower in patients with reduced EF compared to preserved EF (P-value=0.008, mean Reservoir=16.4%±6.4, mean Reservoir=19.5%±5.6, respectively) and (P-value=0.009, mean Booster =9.09%±4.0, mean Booster =11. 9%±4.3, respectively). LA 4ch-reservoir<14.4%, and LA 2ch-reservoir<14.1% was related to LVEDP≥20 mmHg (sensitivity 63.5% and specificity 75%) (sensitivity 77.9% and specificity of 60%) respectively. conclusion LAS is significantly lower in patients with elevated LVEDP (≥ 20mmHg). LAS is significantly lower in patients with reduced EF (< 50%). Both LA-reservoir and LA-booster had a significant relation to predicting LVFP but LA-reservoir is more accurate at both 4-chamber and 2-chamber views. The amount of mean LA-reservoir LAS less than 12.4% and the 4 Ch-reservoir LAS less than 14.4% are associated with LVEDP≥20mmHg. Keywords: left atrium, strain imaging echocardiography, ventricular end-diastolic pressure

Non-invasive assessment of left ventricular (LV) filling pressure by echocardiography is done currently with different modalities including tissue doppler imaging (TDI) of the mitral annulus, mitral inflow velocities, left atrial volume index (LAVI), and right ventricle systolic pressure (RVSP) which are components of left ventricular diastolic function evaluation.

Previous studies comparing the results of these non-invasive echocardiographic methods versus invasively assessed LV Filling pressure (LVFP) have shown that echocardiographic methods have acceptable accuracy [1, 2, 3]. However, with current echocardiographic methods, accurate grading of left ventricular diastolic dysfunction and subsequent evaluation of LV filling pressure (LVFP) are not possible in some patients. According to the latest guideline, these cases, which cannot be placed in a specific group are defined as indeterminate cases [1,4].

A recently proposed non-invasive method for assessment of left ventricular diastolic dysfunction and LV filling pressure is LA longitudinal strain with speckle tracking, which includes the measurement of the reservoir and booster phases of left atrial diastole. A number of studies have shown that measuring LAS provides additional information for the conventional methods of assessing diastolic dysfunction and LVFP [5, 6, 7, 8,9].

In heart failure with preserved EF (HFPEF), new studies have shown that the results of the non-invasive assessment of LVFP by the strain (LAS) during echocardiography are consistent with the results of the invasive assessment. It seems that LAS measurement reduces the need for invasive LVFP assessment [10, 11,12].

In addition, some studies have shown that LAS values are related to the level of fibrosis of the left atrial wall and endocardial thickness, and are helpful [13]. In some other studies, it has been shown that LAS plays a role in determining LVEDP in patients with heart failure with reduced EF (HFREF) [14, 15].

This study aimed to compare LAS in patients with preserved and reduced left ventricular ejection fraction (LVEF)with invasively measured LVFP and determine the LAS cut-off value for high left ventricular end-diastolic pressure (LVEDP). In addition, the role of LAS compared to current echocardiographic modalities in determining the severity of diastolic dysfunction and LVFP was investigated.

Patients who were candidates for coronary angiography in Shahid Madani Hospital from 2020 to 2021, were consecutively recruited in this study. In all patients, medications were prescribed based on existing guidelines and hemodynamics were corrected. Patients were divided into two groups based on left ventricle ejection fraction (EF)equal to or greater than50% and less than 50%. Exclusion criteria included moderate to severe mitral regurgitation (MR), moderate to severe aortic regurgitation (AR), aortic stenosis (AS), mitral stenosis (MS), Mitral supravalvular ring, Cor Triatriatum, and atrial fibrillation (AF) rhythm. Also, patients whose image quality for left atrial (LA) strain lacked appropriate quality were excluded from the study. All patients underwent echocardiography less than 24 hours after coronary angiography and left ventricular catheterization. Data obtained from LA strains were compared to left ventricular end-diastolic pressure (LVEDP) values, which were measured invasively using a Pigtail catheter at the end of diastole, and LA strain values were compared to the results of assessing the severity of left ventricular diastolic dysfunction according to the AHA 2017 guidelines.

All patients underwent two-dimensional echocardiography by Philips epic machine with Matrix array probe.2D grayscale images of the left atrium and left ventricle were taken during the systole and diastole phases and were analyzed offline. Left ventricle end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were measured by the biplane Simpson method. The biplane method of summation disk was used to evaluate the volume of the left atrium. Myocardial deformation was evaluated by speckle tracking method and LA global longitudinal strain was investigated in apical 4-chamber (4ch) and 2-chamber (2ch) LA-focused views at a frame rate between50-70 Hz in conditions where LA can be seen sharply. The LA myocardium was drawn automatically by the software, which was finally traced manually for accurate drawing. All LA myocardium surfaces were manually traced and the left atrial appendage (LAA) and pulmonary veins were removed. By means of Philip’s aCMQ software, the myocardium was divided into 6 parts and the longitudinal strain was measured. Zero point in ECG was defined from the beginning of QRS. LA-reservoir longitudinal strain was measured during peak LV systole and LA-booster was measured during late atrial diastole. LA global strain was calculated from the average of all strains measured from all segments of the left ventricle. Images were deleted during PAC and PVC. Early(E) mitral in-flow was measured by pulse Doppler with a sample volume of 5 mm. Maximum velocity and gradient of tricuspid valve regurgitation flow were measured by CW doppler to determine right ventricle systolic pressure. Tissue velocity was measured in the septal and lateral regions of the mitral valve annulus by tissue doppler imaging (TDI). The average E/e' ratio was measured from the septal and lateral annulus. Following coronary angiography, LVEDP pressure was measured by a pigtail catheter from the left ventricle after zero-level calibration. The pressure tracing information was recorded. Statistical analysis of Quantitative data is expressed as averages and that of qualitative data as percentages.

A total of 125 people were recruited for the study. The number of patients in the preserved EF group (EF≥50%) was 45 and in the reduced EF group (EF<50%) was 80 patients. In the analysis of the above two groups, in terms of the average age and gender of the patients, no significant difference was observed between the two groups (p-value=0.90 and-value=0.89, respectively). A comparison of LVEDP invasively measured by the catheter during angiography showed a significant difference between the two groups (P-value<0.001). It was demonstrated, by a comparison of the two groups, that there were significant differences in terms of diastolic dysfunction indices, including septal and lateral e', left atrial volume index (LAVI), and right ventricular systolic pressure (RVSP) (Table 1). However, evaluation of E/é, LVEDV, E/A, and DT showed no significant difference between the above two groups (Table 1). Comparison LA-reservoir and LA-booster strain of the two groups with preserved EF and with reduced EF, a significant difference was observed (P-value=0.008, mean Reservoir=19.5%±5.6, mean Reservoir=16.4%±6.4, respectively) and (P-value=0.009, mean Booster =11. 9%±4.3, mean Booster =9.09%±4.0, respectively).

The average LVEF in the group with preserved EF (i.e., LVEF≥50%) was 55% and in the group with reduced EF (i.e., LVEF<50%) was 20%.

In the assessment of LV diastolic dysfunction severity based on common criteria, no significant difference was observed between the above two groups (P-value=0.168). In terms of the history of myocardial infarction (MI) and the number of significant coronary artery stenosis, there was a significant difference between the two groups(P-value<0.001 and P-value<0.001, respectively). No significant difference was observed between the two groups in terms of MR severity (P-value=0.58).

Sub-group analysis

In the sub-group analysis based on the level of LVEDP equal to or greater than 20 mmHg and less than 20 mmHg, the number of patients in the LVEDP≥ 20mmHg group was 17 and in the LVEDP<20mmHg group was 118.ComparingLAS between these two groups (with LVEDP≥20mmHg and with LVEDP<20mmHg), showed a significant difference in LA-reservoir values (P-value=0.007, mean LA-reservoir=14.0%±5.5, mean LA-reservoir=18.1%±6.2, respectively). LA-booster strain evaluation between the two groups showed that the value of the mean 4ch-booster also had a significant difference. But no significant difference was observed between the two groups in the evaluation of the mean 2ch-booster (P-value=0.01, P-value=0.10, respectively). A number of other echocardiographic modalities related to diastolic dysfunction showed a significant difference between the two mentioned groups including E/A ratio and DT (P-value=0.025 and P-value<0.001, respectively), but evaluation of é values in the septum and lateral region, the E/é ratio, LVEDV, and LAVI, didn’t show a significant difference. (P-value=0.01, P-value=0.10, respectively) (Table 2). Also, in the evaluation of the two groups, no significant difference was observed in terms of the history of myocardial infarction and the number of significant coronary artery stenosis (P-value=0.645 and P-value=0.319 respectively). In the patients with LVEDP≥ 20mmHg, the average EF was equal to 37.5%±9.0% and in the LVEDP<20 mmHg group, the average EF was equal to 43.3%±8.4% which showed a significant difference (P-value=0.003). There was no significant difference between the two groups in terms of gender.

The cut-off value of LA-reservoir strain to estimate LVEDP above≥20mmHg was analyzed with a receiver-operating curve (ROC). Mean LA-reservoir cut-off <12.4% can determine LVEDP≥ 20mmHg with a sensitivity of 83.7% and specificity of 65%. Also, LA 4ch-reservoir<14.4%, and LA 2ch-reservoir<14.1% can determine LVEDP≥20mmHg (sensitivity 63.5% and specificity 75%) (sensitivity 77.9% and specificity of 60%) respectively (Figures 1 a, b, and c).

This study showed that echocardiographic measurement of LAS could predict elevated LV filling pressure, especially to predictLVEDP≥20mmHg. Both LA-reservoir and LA-booster in the two study groups with preserved and reduced EF (i.e. EF≥50% and EF<50%) were significantly different and were reduced in patients with reduced EF (P-value=0.008 and P-value=0.009, respectively). Moreover, LAS in 4-chamber and 2-chamber views in both LA-reservoir and LA-booster phases show a significant reduction in patients with LVEDP≥20mmHg.Consequently, both echocardiographic views are valuable for the assessment of LAS and can be put into practice. Their values are consistent with the mean LAS.

Our findings showed that current echocardiographic criteria for the evaluation of diastolic dysfunction severity couldn’t predict elevated LV filling pressure compared to invasive measurement(P-value=0.168).

In sub-group analysis, LAS between patients with LVEDP≥20mmHg and LVEDP<20mmHgwere significantly different and was lower in patients with LVEDP≥20mmHg in both LA-reservoir and LA-booster (P-value =0.007 and P-value =0.028, respectively). This analysis also showed a significant relationship between LVEDP≥20mmHg and E/A ratio and DT, but other common echocardiographic criteria for diastolic dysfunction and especially E/é did not show significant relation (Table 2). This indicates LAS can have a complementary role in an investigation for elevated LVFP.

In this study, the average E/é ratio in patients with LVEDP ≥ 20 mmHg was 9.7 ± 2.80 and in the patients with LVEDP< 20 mmHg, was 8.8 ± 2.80 and did not show a significant difference. This indicates that despite the usefulness of the E/é ratio in predicting elevated LV filling pressure and a higher degree of LV diastolic dysfunction, it couldn’t precisely predict LV filling pressure compared to invasive measurement. Our findings showed that LAS is more sensitive than E/é ratio in the assessment of elevated LV filling pressure. Alongside LAS, other more sensitive echocardiographic modalities for determining elevated LV filling pressure were DT and E/A ratios.

The results of our study are almost in line with the results of the Lundberg et al. study [8]. In this study, it was shown that pulmonary capillary wedge pressure (PCWP) values had a significant inverse relation to LAS (P-value<0.001 and r=- 0.54), while PCWP-values had a weak relationship with E/é and LAVI values (P-value<0.001 and r=0.41). The difference between the results of our study and this study is probably related to the method of measuring LV filling pressure. In the aforementioned study, PCWP was used, but in our study, directly measured LVEDP was investigated.

In our study, LAS cut-off value to estimate high LV filling pressure was slightly lower than values that were previously published in the literature. The LA-reservoir strain of less than 20% in a 4-chamber view is related to high LV filling pressure in a study by Amita Singhet et al. [16]. However, in our study, the mean LA-reservoir cut-off value was 12.4% and the 4 Ch-reservoir cut-off value was 14.4% to determine LVEDP≥20mmHg. It seems that studies with lower volume, selecting only a 4-chamber view in previous studies, and choosing a higher LV filling pressure cut-off value (i.e. ≥20mmHg) in our study is related to lower LAS cut-off value in our study.

LAS has relatively high sensitivity with lower specificity for predicting LVEDP ≥20 at mean LA-reservoir<12.45% (Sensitivity=83.7%, Specificity=63.2%). The high sensitivity of this method convinces us to use it in patients whose assessment of high left ventricular pressure cannot be achieved with other non-invasive methods.

The main limitation of our study was the relatively small sample investigated population. The other limitation was related to the sub-group analysis. For the sub-group analysis, we selected a higher LVEDP threshold (i.e., LVEDP≥ 20mmHg) to compare with LAS which results in a lower cut-off value of LAS to predict high LVFP.

This study showed that LAS has a significant relationship with LVEDP≥ 20mmHg and can be a suitable alternative to invasive methods in evaluating LV filling pressure. Furthermore, comparing LAS with other current echocardiographic modalities is more related to severe diastolic dysfunction and elevated LVFP. LAS can be used where the results of other modalities to evaluate high LVFP are borderline and indeterminant. LAS in the 4-chamber and 2-chamber views yields significant results in both methods and both of the above views can be used. The amount of mean LA-reservoir LAS less than 12.4% and the 4 Ch-reservoir LAS less than 14.4% are associated with LVEDP≥20mmHg. The results of the LA-booster, similar to the LA-reservoir, are helpful in measuring LAS.

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

The authors have no relevant financial or non-financial interests to disclose.

Author contributions

All authors contributed to the study conception and design. Mehrnoush Toufan designed, supervised, and, revised the paper. Naser Khezerlouy aghdam; wrote the draft of the manuscript and gave the final approval to submit. Sanaz Pakdel and Hanieh Sakha; did a critical revision of the paper. Morad Shahverdi, Mohamadreza Taban Sadeghi Naser aslanabadi, Ahmad Separham, Sina Mashayekhi and Sanaz Mousavi collected data. And analysis. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tabriz University of medical sciences (Date.../No....)

Consent to participate

Written informed consent was obtained from the parents.

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Table1: Baseline Echocardiographic and Angiographic findings in two groups
	EF		p-value
	<50% (n=80)	³50% (n=45)	p-value
Age	62.01±6.75	58.81±6.36	0.019
Gender(female)	17(21.3%)	10(22.2%)	0.899
4ch reservoir (%)	14.80±6.59	19.45±6.77	<0.001
2ch reservoir (%)	17.68±6.59	20.45±7.26	0.031
Mean reservoir (%)	16.45±6.49	19.58±5.66	0.008
4ch booster (%)	8.65±4.94	10.64±4.79	0.031
2ch booster (%)	10.83±5.15	13.61±6.08	0.008
Mean booster (%)	9.09±4.09	11.98±4.38	0.009
LVEDV (mL)	92.37±16.63	84.28±19.37	0.050
LVEDP (mmHg)	16.96±4.18	14.07±3.88	<0.001
E/A	0.88±0.42	0.95±0.33	0.330
DT (msec)	179.09±55.86	188.50±39.38	0.324
e΄septal (cm/s)	5.73±1.61	7.36±1.96	<0.001
e΄lateral (cm/s)	7.67±2.12	8.92±2.56	0.004
S΄ septal (cm/s)	5.95±1.05	6.78±1.12	<0.001
S΄ lateral (cm/s)	6.66±1.29	7.37±1.98	0.033
E/e΄	9.14±2.88	8.65±2.75	0.361
LAVI (mL/m²⁾	29.62±7.25	26.80±5.71	0.028
RVSP (mmHg)	26.16±6.30	23.66±4.96	0.025
History of myocardial infarction	44(55.0%)	0(0.0%)	<0.001
Diastolic dysfunction grade
I	68(85.0%)	43(95.6%)	0.168
II	9(11.3%)	2(4.4%)
III	3(3.8%)	0(0.0%)
MR severity
Mild	61(76.3%)	37(82.2%)	0.585
Mild to moderate	9(11.3%)	5(11.1%)
Moderate	10(12.5%)	3(6.7%)
CAD severity
1VD	5(6.3%)	9(20.0%)	0.001
2VD	39(48.8%)	6(13.3%)
3VD	22(27.5%)	3(6.7%)
Normal	14(17.5%)	27(60.0%)
Abbreviation: EF; ejection fraction, 4ch; 4 chamber, 2ch; 2 chamber, LVEDV; left ventricle end-diastolic volume, LVEDP; left ventricle end-diastolic pressure, E/A; ratio between the early diastolic inflow velocity (E) to the inflow velocity due to atrial contraction(A), DT; deceleration time, e’; early diastolic myocardial velocity in left ventricle basal septum and basal lateral wall, E/e ratio between the E and eI s’; systolic myocardial velocity in left ventricle basal septum and basal lateral wall, LAVI; left atrial volume index, RVSP; right ventricle systolic pressure,

Table2: Subgroup analysis based on LVEDP (measured invasively)
	LVEDP (mmHg)		p-value
	<20 (n=105)	³20 (n=20)	p-value
Age	60.40±6.65	60.69±6.71	0.901
Gender (female)	24(22.9%)	2(10.0%)	0.242
4ch reservoir (%)	17.07±6.93	13.31±6.80	0.028
2ch reservoir (%)	19.29±6.79	14.77±5.85	0.006
Mean reservoir (%)	18.18±6.29	14.00±5.53	0.007
4ch booster (%)	9.80±5.03	6.97±3.94	0.019
2ch booster (%)	12.19±5.83	9.92±4.29	0.102
Mean booster (%)	11.01±4.33	8.70±3.68	0.028
LVEDV (mL)	88.51±19.15	88.18±14.26	0.956
E/A	0.86±0.33	1.15±0.53	0.025
DT (msec)	187.73±52.47	155.55±30.31	<0.001
e΄septal (cm/s)	6.34±1.94	6.05±1.56	0.527
e΄lateral (cm/s)	8.11±2.41	8.08±2.13	0.952
S΄ septal (cm/s)	6.31±1.19	5.88±0.75	0.125
S΄ lateral (cm/s)	6.92±1.71	6.87±1.00	0.900
E/e΄	8.84±2.80	9.71±2.97	0.211
LAVI (mL/m²⁾	28.50±6.67	29.15±7.99	0.701
EF (%)	43.33±8.40	37.00±9.00	0.003
History of myocardial infarction	36(34.3%)	8(40.0%)	0.645
Diastolic dysfunction grade
I	95(90.5%)	16(80.0%)	0.052
II	9(8.5%)	2(10.0%)
III	1(1.0%)	2(10.0%)
MR severity
Mild	85(81.0%)	13(65.0%)	0.273
Mild to moderate	10(9.5%)	4(20.0%)
Moderate	10(9.5%)	3(15.0%)
CAD severity
1VD	11(10.5%)	2(10.0%)	0.319
2VD	40(38.1%)	5(25.0%)
3VD	18(17.1%)	7(35.0%)
Normal	36(34.3%)	6(30.0%)
Abbreviation: LVEDP; left ventricle end-diastolic pressure ,4ch; 4 chamber, 2ch; 2 chamber, LVEDV; left ventricle end-diastolic volume, E/A; ratio between the early diastolic inflow velocity (E) to the inflow velocity due to atrial contraction(A), DT; deceleration time, e’; early diastolic myocardial velocity in left ventricle basal septum and basal lateral wall, E/e ratio between the E and s’; systolic myocardial velocity in left ventricle basal septum and basal lateral wall, LAVI; left atrial volume index, EF; ejection fraction, MR; mitral regurgitation, CAD; coronary artery disease

No competing interests reported.

Correlation of Left Atrial Strain with Invasively Measured Left Ventricular End-Diastolic Pressure; determining LA strain cut-off value

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Abstract

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