Two-dimensional echocardiography was performed in a certified echocardiography laboratory using a General Electric Vivid E95 ultrasound system (1.5–4.5 MHz transducer). Measurements were made offline from recorded digital loops of three non-foreshortened apical chamber views (4AC, 2AC, and 3AC), ensuring a frame rate of 60–80 frames per second. Analyses of all strain parameters were performed offline in all studies with adequate quality via GE EchoPAC BT 12 software, as recommended in the Expert Consensus Statement [12]. The longitudinal strain was performed for the LV (LV global longitudinal strain, LVGLS) and LAS. All LAS parameters: LAS during the reservoir phase (LASr), LAS during the conduit phase (LAScd), and LAS during the contraction phase (LASct) were measured according to the current recommendations [13, 14]. LASct and LAScd were calculated only in the group of patients with sinus rhythm (SR) during echocardiography. For all strain measurements, while some segments were excluded due to the inability to achieve adequate tracking, global strain values were calculated by averaging the values measured in the remaining segments. The contraction strain index (CSI) was calculated by the formula CSI = (LASr/LASct) × 100.

Reproducibility of the strain measurements was assessed in 20 randomly selected patients, as described previously [15].

All measured LAS values turned out to be significantly lower in the group of patients with AF during echocardiography. For this reason, a comparative analysis was performed for two subgroups — the patients with SR and the patients with AF during TTE.

Left atrial pressures measurements

The LA was accessed through a double transseptal puncture using an 8.5 transseptal sheath, a Swartz™ SL0, and a BRK™ needle (Abbott Medica, Plymouth, MN, USA). The LAP was measured directly, soon after the transseptal puncture, via a transseptal sheath with a special converter for invasive blood pressure measurement (B. Braun Melsungen AG, Melsungen, Germany) and linked with the Philips Azurion image-guided therapy platform (Philips Medical Systems DMC GmbH, Hannover, Germany). Three values were measured automatically in the LA: highest (LAP max), lowest (LAP min), and mean (LAP mean).

Statistical analysis

Statistical analyses were conducted with Statistica 13.0 (StatSoft Inc., Tulsa, OK, USA). The distribution and normality of data were assessed with the Shapiro-Wilk test. Continuous variables were presented as means (standard deviation [SD]) or medians (interquartile range [IQR]: 1st–3rd quartile), whereas categorical variables were presented as absolute and relative values (percentages). In a comparative analysis, the student’s t-test was used for normally distributed data, whereas the Mann-Whitney U-test was used for data with non-normal distribution. A chi-square test with the Yates correction was used for categorical variables. A two-tailed p-value of <0.05 was considered statistically significant. For comparison, the study population was divided into 3 terciles according to the distribution of LASr values and separately from the SR and AF groups, where the first tercile was for the subjects with the smallest values of LASr, and the third tercile was for the subjects with the highest values. The correlation of echocardiographic findings, including LAS parameters with LAP values, was analyzed separately for the SR and AF groups using Spearman’s correlation analysis (with the rs correlation coefficient as the main analysis). A Receiver Operating Characteristic (ROC) curves with Area Under Curve (AUC) were calculated to estimate the cut-off value for LASr as a predictor of elevated mean LAP (≥15 mm Hg) in the AF and SR group.

RESULTS

Baseline characteristics

A total of 172 ablated AF patients were enrolled in the study (Figure 1).

In total, 98 patients presented with SR during echocardiography, and 74 had AF. TTE and TEE were performed immediately prior to ablation, and the heart rhythm during both echocardiography examinations and ablation was the same in all enrolled patients. The baseline characteristics of the study population, including demographic, clinical, and echocardiographic data, are presented in Supplementary material, Table S1.

Patients in the AF group were compared to those in the SR group and did not differ in terms of clinical parameters. However, they were characterized by a significant enlargement of LA assessed by the LA volume index (LAVI), reduced LV systolic function assessed by LV ejection fraction (LVEF) and LVGLS and had a more frequent occurrence of LV hypertrophy and lower LASr values. Moreover, analysis of LAS revealed lower values than those previously reported as normal (values reported as normal: 39% for LASr, –17% for LASct, and –23% for LAScd) [16] in both groups. Detailed LAS values are given in Supplementary material, Table S1. Mean and peak LAP, when measured directly during ablation, were significantly higher in the AF group.

Characteristics of patients with lower LASr values

In both assessed groups (AF and SR), the patients with lower LASr values (first tercile) were significantly older (P = 0.046; P <0.0001, respectively) and more often female (P = 0.006; P = 0.01, respectively). Moreover, patients in the first tercile in both groups, compared to those in the third tercile, had a significantly larger LA (assessed by LAVI) and more impaired diastolic LV function parameters by the e’ average value and the E/e’ ratio.

The patients in the SR group also had more impaired systolic LV function (assessed by LVEF and LVGLS), more LV muscle mass (assessed by LV mass [LVM] and the LVM index [LVMI]), lower LAEF, longer duration of PA-TDI, and significantly lower LASct and LAScd values. In addition, these patients had a significantly higher frequency of concomitant diseases, such as heart failure, hypertension, and vascular disease.

The remaining differences obtained in the comparison between both groups with lower LASr values are presented in Table 1 (AF) and Table 2 (SR).

No differences were found between the patients with lower and higher LASr values and clinical manifestation of AF (EHRA class).

The analysis of our population showed a negative correlation between age and all LAS values in the entire study group and the group with SR (Supplementary material, Table S2).

Correlation of echocardiographic parameters with the LAP value

The most prominent correlations were found in the SR group of patients between LASr and LASct values, as well as the E/e’ ratio and LAP values. As for the results of the correlation analysis in the other groups (all groups and the AF group), the main differences were less noticeable, especially in the AF group. In the AF group, the most potent correlation was between the E/e’ ratio and the LAPmax and LAPmean values. Detailed data are summarized in Tables 3, 4, and 5. In the SR group the cut-off value of LASr estima­ting elevated mean LAP (≥15 mm Hg) was 21.88, with 71% sensitivity and 82% specificity (AUC, 0.81; 95% CI, 0.72–0.90; P <0.0001). In the AF group, the corresponding LASr cutoff value was 11.25, with 72% sensitivity but 65.5% specificity (AUC, 0.66; 95% CI, 0.53–0.80; P = 0.016).

DISCUSSION

In this prospective, observational study, we investigated the clinical and echocardiographic characteristics of AF patients undergoing ablation. Long-term AF can lead to structural, electrical, and functional LA remodeling. As a result, AF patients have an increased risk of mortality, thromboembolic events, stroke, and heart failure [16]. STE is well validated as a quantitative assessment tool for regional and global LA function [17, 18]. This method makes it possible to detect early subclinical LA dysfunction in many cardiac diseases. The impairment of LASr can be detected in AF patients even before atrial dilatation has occurred. In the recent study, it was found, that LASr >22% is a cut-off value for SR maintenance after catheter ablation [19]. In our study, all patients undergoing ablation had lower values of LAS than those previously reported as normal [16]. These results applied to patients with SR and those with AF during TTE. However, the LASr values were particularly lower in patients during AF. This occurrence prompted us to analyze both groups of patients separately. Kuppahally et al. [20] showed that LA wall fibrosis evaluated by delayed enhancement magnetic resonance imaging is inversely related to LAS values, and these are related to the AF burden. The reduced LAS value is considered an early non-invasive marker of the amount of LA wall fibrosis [21]. It is unclear, whether atrial fibrosis in AF patients is the result of AF itself or if it is related to other conditions, such as specific fibrotic atrial cardiomyopathy [22]. As experts point out, both mechanisms are possible and atrial arrhythmias can also induce atrial remodeling that contributes to the progression of AF [23]. Regardless of the mechanism, structural AF remodeling is more frequent in patients with persistent AF. This can partly explain lower LAS values found in our patients with AF during TTE.

The comparative analysis of the 2 groups of AF patients (SR vs. AF groups) undergoing ablation also revealed that the patients from the AF group were characterized by not only significant enlargement of the LA but also by reduced LV systolic function and more frequent occurrence of LVH. In a group of 1 483 AF patients, Kuo et al. [24] demonstrated that impaired LV systolic function assessed by myocardial deformation (LVGLS, the strain rate) was common in patients with AF. Moreover, LV deformations measurements in AF patients provided an independent prognostic value over conventional echocardiographic measures with an improved risk prediction. In the mentioned study, 67.8% of the entire study cohort had abnormal LVGLS (defining the value of LVGLS –14.7% as the abnormal GLS cut-off). Moreover, the patients with permanent AF had markedly lower GLS compared to those with paroxysmal AF (–11.5% vs. –14.4%). In our study, these values were better (–14.1% vs. 19.7%) for the AF and SR groups, respectively, but also more impaired in the AF group. Reduced LVGLS values in the group of patients with AF may worsen their prognosis. Dons et al. [25] reported that decreasing the GLS/√(RR) interval ratio was associated with an increased risk of an adverse outcome in a group of 204 AF patients during 2.4 years of follow-up.

Per reports to date, reduced LAS values are strongly correlated with a worse prognosis for patients with AF. Therefore, an important result of our study is characterizing the group with the lowest LASr values as the group with the worst prognosis.

Characteristics of patients with the lowest LASr values, both assessed groups demonstrated that the patients with the lowest LASr values (first tercile) were significantly older and more often female (P = 0.006; P = 0.01, respectively). Studies on the relationship of the LAS values with age did not provide unequivocal results. Previous studies have reported that the LASr value gradually decreases with age, regardless of the population studied, while the LASct values remain rather unchanged [26, 27]. Most of the data show no significant difference between healthy men and women with respect to LA strain parameters [14]. However, studies conducted on patients with AF showed lower LASr values among women with AF [28].

Regarding the remaining parameters studied, the differences in the characteristics of the group with the lowest LAS values were mainly observed in the SR group. These patients were characterized by disturbances in both the structure (a larger LA, higher LVMI) and function (lower LVEF, LVGLS, LASct, LAScd, LAEF, e’ average; higher E/e’; longer duration of PA-TDI) of the left heart chambers. In addition, these patients had a higher frequency of concomitant diseases, such as heart failure, hypertension, and vascular disease. Thus, this group is most likely to be at the highest risk of AF recurrence after ablation. However, confirmation requires follow-up studies.

Correlations between the LAS values and the LAP present another interesting issue. Individual LAS values reflect different phases of LA function and allow evaluation of phasic LA function throughout the cardiac cycle: LASr reflects LA compliance, LAcd as a conduit for LV filling, and LASct as a parameter of LA booster pump function. Likewise, LAP values are measured at different phases of LA function: LAPmax as the maximum height of the v wave and LAPmin as the minimum of the x trough during SR or the lowest value of the pressure curve during AF [29]. Although the greatest clinical utility concerns LASr in the case of echocardiography and LAPmean in the case of hemodynamic measurements, the importance of other LAS and LAP values is also increased. A study revealed that both LAPmax and LAPmean were significantly higher in patients with AF recurrence after catheter ablation [30]. In that study, in multivariate analysis, an LAPmax >18 mm Hg was significantly associated with an elevated risk for AF recurrence (hazard ratio [HR], 3.8). Moreover, the LAPmax showed a better correlation with AF recurrence than the LAPmean (AUC LAPmax = 0.75 vs. AUC LAPmean = 0.73). Park et al. [10] also confirmed that LAPpeak during sinus rhythm was an independent predictor of clinical recurrence of AF (hazard ratio, 1.887; 95% CI, 1.063–3.350; P = 0.028). Similar results were obtained in a study by Roh et al. [31], where LAPmax was compared with LA-late gadolinium enhancement extent on cardiac magnetic resonance imaging. Linhart et al. [32] revealed LAPmean was significantly higher in patients with recurrence of AF (13.4 ± 7.1 vs. 11.0 ± 5.2 mm Hg; P = 0.007). For all mentioned above reasons, we have decided to assess both echocardiographic parameters (LASvalues) and hemodynamic (LAPvalues) assessment of the LA function in its various phases.

In our study, the strongest correlations were found in the SR group, where LAP was correlated with LASr and LASct values as well as the E/e’ ratio. These high LAP values measured during ablation proved to be independent predictors of clinical recurrence of AF and were associated with advanced LA remodeling [10]. It is difficult to explain weaker correlations between LAS and LAP values in the AF compared to the SR group. It is worth mentioning that Hewing et al. [33] obtained similar results. In patients with SR, LA reservoir, conduit, and contractile function are inversely correlated with hemodynamic parameters. However, in AF patients, there were no significant correlations between LA reservoir function and invasively obtained hemodynamic parameters.

In summary, the highlighted AF patients with the lowest LASr are older, more often female, have a larger LA, and have more impaired LV diastolic parameters. The most prominent correlations were found in the SR group, where low LASr, low LASct, and high E/e’ ratio values were associated with higher LAP.

Clinical utility

Direct measurement of LA pressures during ablation is an accurate but invasive method for assessing LA function. Non-invasive echocardiographic assessments of LA anatomy and function include more than volumetric and Doppler analyses. The use of the new STE method may be helpful, and it appears to be superior to conventional echocardiographic parameters of LA analysis [14, 15]. Assessment of LA function and structure has been used to predict both risks for thromboembolic events and the success of restoring SR after AF ablation [34, 35]. Characterizing the group of patients with the lowest LAS values may help predict the likelihood of SR maintenance after catheter ablation using LAS analysis. It would be quite valuable in selecting candidates for catheter ablation. High correlation of echocardiographic LA strain measurements with LA pressures could represent an attractive alternative approach for estimating hemodynamics in a group of AF people with SR.

Limitations

In the presented study, we assessed state-of-the-art strain parameters, and the measurements were performed by an experienced echocardiographer in accordance with the current recommendations. The main limitations were the small sample size and the lack of follow-up; thus, we can only assess the basic characteristics of the presented groups of patients and cannot assess whether the prognosis of the group with the lowest LAS values regarding the recurrence of arrhythmia is worse compared to other groups of patients.

Supplementary material

Supplementary material is available at https://journals.viamedica.pl/kardiologia_polska.

Article information

Conflict of interest: KK is a shareholder of Abbott. Other authors declare no conflict of interest.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.

How to cite: Uziębło-Życzkowska B, Krzesiński P, Jurek A, et al. Correlations between left atrial strain and left atrial pressures values in patients undergoing atrial fibrillation ablation. Kardiol Pol. 2021; 79(11): 1223–1230, doi: 10.33963/KP.a2021.0113.

REFERENCES