European Journal of Cardiovascular Medicine

Atrial fibrillation (AF) is one of the most common arrhythmias, with an estimated prevalence between 2 and 4% worldwide. [1] The burden of the disease is rising due to aging of the population and increasing prevalence of cardiovascular disease.[2] It can occur at any age but is very rare in children and becomes extremely common in the elderly, with a prevalence approaching 20% in patients >85 years of age.[3]

It is characterized by irregular and rapid electrical impulses in the atria, leading to ineffective atrial contraction and increased risk of blood stasis and thromboembolic events. Additionally, AF has been recognized as a major contributor to the development and progression of heart failure.[4]

Heart failure is a complex clinical syndrome characterized by the heart's inability to adequately pump blood to meet the body's demands. It is associated with significant morbidity, mortality, and healthcare costs. The presence of AF in heart failure patients further exacerbates the clinical course, leading to worse outcomes and increased hospitalizations.[5]

 The pathophysiology underlying the relationship between AF and heart failure involves various structural and functional changes in the heart. Biatrial remodeling, which refers to alterations in the size, shape, and function of both the left and right atria, has been recognized as a key feature in this process. It is driven by a combination of electrical, mechanical, and neurohormonal factors associated with AF.[6] Understanding the extent and patterns of biatrial remodeling in AF is crucial for elucidating the mechanisms that contribute to heart failure development. Traditional echocardiographic parameters, such as atrial size and function, have provided valuable insights into atrial remodeling. However, they often lack sensitivity and specificity in capturing subtle changes in myocardial contractility and deformation.

In recent years, two-dimensional strain echocardiography has emerged as a powerful imaging modality for assessing myocardial deformation and contractility. By analyzing strain, strain rate, and other parameters, two-dimensional strain echocardiography provides a comprehensive evaluation of regional and global myocardial function. This advanced technique enables the quantification of atrial strain, which can detect early changes in atrial mechanics and identify specific remodeling patterns associated with adverse clinical outcomes.[7].

Type of Study: This was a prospective observational and corelational trial

Place of study and Duration: June 2021 to June 2022, first 12 months were utilized for data collection and remaining periods were used for analysis, report writing and finalization.

Sample Size: This was accomplished by 50 patients.

Inclusion:

• Documented paroxysmal, persistent or permanent AF on electrocardiography
• Age > 18 years;
• Provision of patient consent

Exclusion:

• Valvular AF (mitral stenosis, defined as an area < 2 cm2; mitral, aortic or tricuspid regurgitation greater than moderate to severe; moderate or severe aortic stenosis; mechanical or biological prosthesis)
• Contraindication to anticoagulant treatment
• Severe psychiatric history
• Unlikelihood to attend follow-up

Statistical Analysis: For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 5). Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests, which compare the means of independent or unpaired samples, were used to assess differences between groups. Paired t-tests, which account for the correlation between paired observations, offer greater power than unpaired tests. Chi-square tests (χ² tests) were employed to evaluate hypotheses where the sampling distribution of the test statistic follows a chi-squared distribution under the null hypothesis; Pearson's chi-squared test is often referred to simply as the chi-squared test. For comparisons of unpaired proportions, either the chi-square test or Fisher’s exact test was used, depending on the context. To perform t-tests, the relevant formulae for test statistics, which either exactly follow or closely approximate a t-distribution under the null hypothesis, were applied, with specific degrees of freedom indicated for each test. P-values were determined from Student's t-distribution tables. A p-value ≤ 0.05 was considered statistically significant, leading to the rejection of the null hypothesis in favour of the alternative hypothesis.

Table 1: Anthropometric Variables

Table 2: Incidence of CHA2DS2-VASC score ≥2

Table 3: Distribution depending on the Rhythm at Baseline and at after 6 month

Figure 1: Comparison of Atrial Volumes (Indexed) between 2 groups Baseline and after 6 month

AF-SR (n= 33)

AF-AF (n= 17)

Figure 2: Correlation of biatrial remodeling with heart failure

The anthropometric variables are summarized as follows: The mean height is 159.52 ± 5.92 cm, with a mean weight of 68.74 ± 6.82 kg. The average BMI is 27.07 ± 3.51 kg/m², and the mean body surface area (BSA) is 1.52 ± 0.16 m². These values represent the central tendency and variability for each measurement, offering insight into the general characteristics of the sample. CHA2DS2-VAScore (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes mellitus, stroke/transient ischaemic attack/ thromboembolism [doubled], vascular disease, age65-74 years, sex category [female]) risk score was ≥ 2 was present in 19 (38%) patients. The distribution according to the sinus rhythm at baseline at 6 month follow up. The participants was divided depending on the rhythm at M0 (baseline) and M6 (6 month follow up): AF at M0 and SR at M6 (AF-SR) in 33 (66%) patients and AF at M0 (baseline) and M6 (6 month follow up) (AF-AF) in 17 (34%) patients. In the study, the RA and LA volumes were measured for two groups: AF-SR (n=33) and AF-AF (n=17). For RA volume, the AF-SR group showed a significant decrease from baseline (33.06 ± 1.71 ml/m²) to 6 months (27.00 ± 1.52 ml/m²), with a p-value of <0.0001. In contrast, the AF-AF group exhibited no significant change in RA volume, with values of 40.55 ± 2.31 ml/m² at baseline and 46.64 ± 3.12 ml/m² at 6 months (p = 0.331). Between-group comparisons revealed a significant difference in RA volume at both baseline (p = 0.008) and 6 months (p <0.0001). Regarding LA volume, the AF-SR group experienced a significant reduction from baseline (44.51 ± 2.06 ml/m²) to 6 months (39.24 ± 1.34 ml/m²), with a p-value of <0.0001. However, the AF-AF group did not show a significant change in LA volume, with values of 50.56 ± 2.12 ml/m² at baseline and 50.82 ± 2.96 ml/m² at 6 months (p = 0.167). There was no significant difference between the groups at baseline (p = 0.820), but a significant difference was observed at 6 months (p < 0.0001). In summary, AF-SR demonstrated significant changes in both RA and LA volumes over 6 months, while AF-AF showed no significant changes. Additionally, there were significant differences between the two groups in both RA and LA volumes at the 6-month mark. The incidence of heart failure according to biartial remodelling. Incidence of heart failure was significantly higher among patients in AF-AF group (52.9% in AF-AF group vs. 9.1% in AF-SR group), (p value = 0.0005).

Atrial fibrillation (AF) is the most common persistent arrhythmia and one of the most significant cardiovascular risk factors. Moreover, AF is also associated with a 1.5-fold to twofold increased risk of all-cause mortality.

Identifying patients who would be benefited from rhythm rather than rate- control remains challenging. Even though refractory symptoms are the primary indication for rhythm-control; recent evidence suggests that it might also translate into better long-term outcomes.[8] Characterization of the anatomical and functional atrial substrate of AF may support the choice between rhythm and rate-control because left atrial (LA) dilation and fibrosis are associated with AF.[9]

Maintenance of sinus rhythm with the procedure has been shown to result in a reduction of the left atrial (LA) size assessed by two-dimensional (2D) echocardiography and magnetic resonance imaging.[10]

Conventionally, TTE has been used to observe anatomical changes of LA following remodeling in the AF patients; however, it has been increasingly replaced with two-dimensional (2D) speckle tracking echocardiography in order to evaluate LA function.[11] Most studies that report the association between LA and LAA function[16,28-30] were carried out on occidental populations.

The association between left atrial (LA) size and non- valvular atrial fibrillation (AF) has already been established. Observations from the Framingham study established LA size as an independent echocardiographic indicator of AF. Recently, in addition to LA size, LA function can also be evaluated using three- dimensional (3D) volumetric or two-dimensional (2D) strain atrial parameters.[12] Elevated atrial size and impaired atrial function are benchmarks of atrial remodelling, an important underlying substrate in AF. The atrial remodelling technique is not simple and poorly understood, and it includes atrial fibrosis, hypocontractility, fatty infiltration, inflammation, vascular remodelling, ischaemia, ion channel dysfunction and Ca2+ instability. The phrase ‘‘atrial cardiomyopathy’’ has been suggested to refer to ‘‘any complex of structural, architectural, contractile, or electrophysio- logical changes affecting the atria with the potential to produce clinically relevant manifestations’’.[13]

Earlier studies have established the important role of transthoracic echocardiography (TTE) in the evaluation of LA remodelling in AF in various clinical settings: to assess the effect on LA size, volume and function, before and after catheter ablation; to identify patients with a high risk of AF recurrence; and, more recently, to predict AF in cryptogenic cerebrovascular accidents. However, right atrial (RA) remodelling has been poorly investigated in AF, and few studies have focused on biatrial remodelling in AF.[14]

In this perspective the present study was carried out with the aim to evaluate LA and RA remodelling in AF using TTE-derived global Left Atrial reservoir strain according to rhythm outcome at mid-term follow up and to correlate with heart failure.

The present study was carried out in the Cardiology Department, IPGMER and SSKM Hospital during the period from June 2021 to June 2022. A total of 50 patients having non valvular AF attending Cardiology Emergency and OPD were included after meeting the inclusion and not having any of the exclusion criteria.

The observations of the present study are as follows: Majority of the study subjects were aged from 61-70years (42%) followed by 51-60 years (28%) and 71-80 years (20%) with a mean age of 62.80 ±10.50 years.

Out of 50 patients in the present study 33 (66%) were males and 17 (34%) were females with a male to female ratio of 1.94:1.

The mean height, weight, BMI and BSA was 159.52 ±5.92cm, 68.74 ±6.82kg, 27.07 ±3.51 kg/m2 and 1.52 ±0.16 m2 respectively.

Paroxysmal AF was present in 35 (75%) patients in the present study while 15 (30%) had persistent AF.

The participants was divided depending on the rhythm at M0 (baseline) and M6 (6 month follow up): AF at M0 and SR at M6 (AF-SR) in 33 (66%) patients and AF at M0 (baseline) and M6 (6 month follow up) (AF-AF) in 17 (34%) patients.

At M0 (baseline) and M6 (at 6 month follow up), LA 4C, 2C and global strain was assessed in all patients. Between M0 and M6, in the AF-SR group, we found there was significant increase in LA 4C, 2C and global reservoir strains (p value = 0.017, 0.024 and 0.041 respectively), while in AF-AF group we observed a significant decrease in LA 4C, 2C and global strains at 6 month follow up while comparing with baseline levels.

This particular observation indicates that negative remodeling of LA was seen in AF-AF group while in AF-SR group there was a reverse remodeling. H Muller et al in their study assess the effect of PVI on biatrial anatomical remodelling using real-time 3DE. Their study reported that Left atrial volume was significantly reduced at follow-up when compared with baseline (51+16 vs. 60+21 mL, (P value = 0.001). The same occurred with RA volume (43+17 vs. 50+20 mL, P ¼ 0.001). The reduction in the LA volume was more marked in patients with chronic than in those with paroxysmal AF (17+16 vs. 6+17 mL, P ¼ 0.017). Patients with AF recurrence (23%) showed similar atrial volume reduction compared with those who were seemingly cured. They concluded that three-dimensional echocardiography shows evidence of biatrial anatomical reverse remodeling after RFCA for AF. A reduction in the atrial volume occurs despite recurrence of AF.

Their data are in contrast to previous publications, which have shown the reduction in the LA size only in patients seemingly free of AF at follow-up.[15]

Ma et al, in a meta-analysis of eight studies, demonstrated that patients with recurrence of AF were characterized by lower LA strain compared with patients without AF recurrence.[16]

1. Soulat-Dufour et al evaluated right atrial (RA) and left atrial (LA) remodelling in AF using global atrial reservoir strain and three-dimensional (3D) atrial volumes, according to rhythm outcome at mid-term follow-up. Very likely to the present study they reported that between M0 and M6 in the AF-SR group, they found: significant decreases in Max 3D RA Volume (P = 0.020), Min 3D RA Volume (P = 0.0008), Max 3D LA Volume (P = 0.001) and Min 3D LA Volume (P = 0.0021). significant increases in global RA and LA reservoir strain (both P < 0.0001) was found in AF-SR group. There was no significant difference with regard to these variables in the AF-AF and SR-SR groups. At the end of the study they concluded volume and strain analyses were useful in the evaluation of RA and LA reverse remodelling in successfully cardioverted patients with AF.

AF results in biatrial enlargement [17], and restoration of SR after ablation or cardioversion causes to biatrial reverse remodelling, with a very few reported data on RA structural and functional remodelling. An electro-physiology researchwith detailed biatrial electroanatomic mapping has exhibited that AF is linked with remodelling technique affecting both the atria. This observation suggests that RA remodelling could establish an accurate correlation with LA remodeling. RA structural remodelling in AF has been assessed using TTE and magnetic resonance imaging (MRI). Previous studies exhibite the noteworthy decrease in 3D RA volume after restoration of SR. Study by Therkelsenet al [18], reported only the RA volume normalized 180 days after cardioversion in comparison with healthy controls. This may emphasize the greater and faster capacity of the RA to reverse structural remodelling. In the present study as well study, we observed RA structural reverse remodellingrestricted to the AF-SR group at six month follow up (M6), with significant decreases in RA volume, to the same magnitude as reported with LA reverse remodeling.

Our study also reported that at M0 (baseline) and M6 (at 6 month follow up), global LA strain was assessed in all patients. Between M0 and M6, in the AF- SR group, we found there was significant increase in global LA reservoir strains (p value = < 0.0001), but significant decrease was found in terms of LA reservoir strain in the AF-AF group. Similar to the present study L. Soulat- Dufour et al in their study also found that global RA strain was assessed in all patients, and mean global LA strain was assessed in 40 (83.3%)patients. Between M0 and M6, in the AF-SR group, we found significant increases in global RA and LA reservoir strains (both P < 0.0001), but no significant differences in the AF-AF and SR-SR groups.[19]

Incidence of heart failure was significantly higher among patients in AF-AF group (52.9% in AF-AF group vs. 9.1% in AF-SR group), (p value = 0.0005). This observation suggests that LA remodelling is early predictor for detection of patients with heart failure.

In conclusion, atrial fibrillation (AF) remains the most common arrhythmia, with increasing prevalence. Atrial arrhythmogenic remodeling, particularly in the left atrium (LA), plays a key role in AF development and persistence. While bi-atrial remodeling is often present, right atrial (RA) remodeling remains underexplored. This study evaluated LA and RA remodeling using transthoracic echocardiography (TTE)-derived global LA reservoir strain and RA volume. Findings suggest that structural and functional remodeling significantly decrease LA global reservoir strain, while reverse remodeling leads to its increase. Patients with persistent AF exhibited greater atrial remodeling and functional impairment compared to those with paroxysmal AF. Furthermore, LA remodeling emerged as an early predictor of heart failure.