Correlation of left atrial strain with left ventricular end-diastolic pressure in patients with normal left ventricular ejection fraction

Between June 2018 and November 2019, we prospectively studied 55 patients with LVEF ≥ 50% (mean age, 63 years old, 38 men [69.1%]) referred for left heart catherization, and echocardiography was completed within 12 h before or after catheterization. Patients with confirmed or suspected coronary artery disease underwent left heart catheterization. Those with Atrial fibrillation, ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), moderate or greater tricuspid regurgitation, moderate or greater mitral regurgitation, any mitral or aortic stenosis, prosthetic valves, hemodynamic instability or poor echocardiography imaging were excluded. The study was approved by the institutional enrolling board of the first affiliated hospital of Soochow university.

Echocardiographic measurements were performed by two board-certified echocardiographers blinded to the LVEDP who finalized each measurement by consensus. The two-dimensional echocardiographic imaging of all subjects was performed by GE Vivid E9 and GE Vivid E95 equipment (Norway) 2.5 MHz transducer. The LA dimension was measured in the parasternal long-axis view at the ventricular end-systole. Mitral diastolic inflow was interrogated using pulsed-wave Doppler from the apical four-chamber view at the level of the mitral leaflet tips. Mitral early diastolic peak (E-wave) and late peak (A-wave) velocities and E/A ratio were measured. In the apical two and four-chamber views including the entire left atrium, LAV was determined using biplane Simpson method at end-systolic frames just before mitral valve opening (maximal left atrial volume, LAVmax), at end-diastolic frames coincided with the R-wave on the electrocardiogram (minimal left atrial volume, LAVmin) and during mid-diastole phase which is before electrocardiographic P-wave (left atrial volume before A wave, LAVpre-A). Values were then indexed to the body surface area (LAVimax, LAVimin and LAVIpre-A). left atrial ejection fraction (LAEF) were calculated by LAVImax minus LAVImin. In addition, the septal mitral annulus early (E′) velocity was measured by tissue Doppler imaging, and the E/E′ ratio was calculated using a cutoff value > 15 to represent elevated LV filling pressure. LVEF was measured using Simpson’s method, which was used as a standard index of global LV systolic function. All echocardiographic measurements used in the analysis were averaged from 3 heart beats.

The two-dimension strain analysis package available on the Echo PAC work station (GE Healthcare) was used to measure the LA strain and strain rate. Similar to the left ventricle, the complete myocardial region of interest (ROI) of the LA is defined by the endocardial border. An adjustable ROI with a default width of 3 mm is recommended. The user can adjust the size and shape to include the thickness of LA wall and to avoid including the pericardium. The software divided the atrial endocardium into six segments, poorly displayed segments were automatically rejected by the software and excluded from the analysis. The global longitudinal strain and strain rate curves were generated by the software for each apical view. The operator could repeat the imaging or change software parameters such as the width of the region of interest and the smoothing functions to obtain satisfactory tracking. Apical four and two-chamber views were obtained in three consecutive heart beats, and electrocardiograph was recorded in the meantime. The LA strain is defined as the absolute strain value in LA three phases, which includes reservoir strain in systole (LASr), conduit strain in early diastole (LASct) and contraction strain in late diastole (LAScd). LV end-diastole was defined as initial zero reference point. The respective strains are LASr, calculated as difference between onset of filling and end-diastole; LAScd, calculated as difference between onset of atrial contraction (before start of Doppler A-wave) and onset of filling; LASct, calculated as difference between end-diastole and onset of atrial filling. The global strain was calculated as the average of both respective values form both views. (Fig. 1).

A 6F pigtail catheter was placed in the left ventricle to obtain the invasive LV pressure. Excluding the unstable baseline of LV filling pressure, LVEDP was measured by mean values of 3–5 cardiac cycles. Image J was used to measure LVEDP at the beginning of QRS on Electrocardiography. A LVEDP value > 16 mmHg was defined as elevated LV filling pressure [3, 11]. LVEDP values were measured by two investigators blinded to echocardiographic data.

Analyses were performed using the SPSS 25.0. Continuous variables which are normally distributed are presented as mean ± SD. Variables that are not normally distributed will be presented as median with inter-quartile ranges (IQR = 25th–75th percentile). T test and Mann–Whitney U test was used for comparison of groups. Categorical variables are expressed as absolute numbers and respective percentages, categorical variables were compared with chi squared tests. LA strain and LV diastolic dysfunction parameters such as septal e′ velocity, lateral e′ velocity, E/e′, E/A, LAEF, tricuspid regurgitation velocity, LAVI and LVEDP were evaluated using univariate logistic regression analysis. Differences with p values less than 0.05 were considered significant. The independent predictive value of echocardiographic variables was evaluated in three different multivariate model. Predictors of elevated LVEDP with p value ≤ 0.12 in the univariate analysis and age, were included in multivariate models. In our three models, LASr LASct and LAScd were analyzed separately due to their multicollinearity, with other control variables the same. The C-statistic was calculated in each model, in order to allow comparison between them. Receiver operating characteristics (ROC) curves were created to compare the performance of multiple variables in determining increased LVEDP.

Patients’ clinical characteristics and echocardiographic measurements are shown in Table 1. LVEDP was elevated in 35 patients (63.6%), and normal in 20 (36.4%) patients. The study population (n = 55) has a mean age of 63 ± 10.0 years, among which 17 (31%) were female. Most characteristics are similar in both groups, such as age, diabetes, CAD etc. Significant differences between the two groups were observed in LA strain (LASr, LASct, LAScd). Vital signs were not significantly different when echocardiography and catheterization were performed.

The LA strain and LVEDP are correlated negatively: LASr (p < 0.001, R = 0.662), LASct (p < 0.001, R = 0.575), LAScd (p < 0.001, R = 0.456). No significant correlation was found between the LVEDP and E/e′ (p = 0.493). Figure 2 is scatter diagram of LA strain and E/e′. LASr has a stronger correlation with LVEDP, compared to other variables observed in our study.

The predictive values of LASr, LASct and LAScd were evaluated in three different multivariate logistic regression analyses (Table 2), which contained the same variables (age, Mitral A, HR and hypertension), differing only by control variables. The LASr, LASct and LAScd were independent predictors for LVEDP > 16 mmHg in their respective models. The model shows that LASr has a higher C-statistic when compared to the model with LASct and LAScd.

Figure 3 shows that LA strain has good diagnostic accuracy for LVEDP > 16 mmHg. The area under the curve (AUC) for LASr is 0.914 (cutoff value is 26.7%, sensitivity is 90%, specificity is 82.9%). For LASct, the AUC is 0.769 (cutoff value is 12.0%, sensitivity is 85%, specificity is 57%). The AUC of LAScd is 0.844 (cutoff value is 11.0%, sensitivity is 90.0%, specificity is 68.6%), which shows that LASr can predict LVEDP better than LASct and LAScd.

The sample size in this study is limited, so selection bias still exists, however increasing the number of individuals will reduce the selection bias. The study was conducted on patients from only one medical center, which might impact the population selected and, consequently, the variables analyzed. Left atrium imaging is difficult to obtain and the image definition is poor in some cases, and some echocardiographic images have poor repeatability in left atrial strain.