European Journal of Cardiovascular Medicine

Diastolic dysfunction (DD) represents a pathophysiological state in which the left ventricle (LV) exhibits impaired relaxation and/or increased chamber stiffness, leading to abnormal ventricular filling, elevated left atrial (LA) pressures, and eventual progression to heart failure with preserved ejection fraction (HFpEF). HFpEF accounts for nearly 50% of heart failure cases worldwide and is associated with significant morbidity, mortality, and health care costs, despite preserved left ventricular systolic function. Detecting diastolic dysfunction at an early stage is critical for initiating timely therapeutic interventions and preventing adverse clinical outcomes.^[1]

Traditionally, the diagnosis of diastolic dysfunction relies on echocardiographic parameters, as recommended by the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI). Key indices include mitral inflow velocities (E/A ratio), tissue Doppler imaging (TDI) of mitral annulus velocities (e′), the E/e′ ratio, pulmonary vein flow, tricuspid regurgitation (TR) velocity, and left atrial volume index (LAVI). While these parameters remain the cornerstone of diastolic function assessment, each has inherent limitations related to preload dependence, heart rate variability, operator dependence, and inability to consistently detect subclinical disease.^[2][3]

In recent years, two-dimensional speckle-tracking echocardiography (2D-STE) has emerged as a novel, non-invasive imaging modality capable of assessing myocardial deformation by tracking natural acoustic markers (speckles) in the myocardium. Strain imaging quantifies myocardial deformation in percentage change of length, providing more sensitive detection of subtle myocardial dysfunction before changes in conventional echocardiographic parameters or ejection fraction occur. Initially used for left ventricular global longitudinal strain (LVGLS) assessment, speckle-tracking has now been extended to the evaluation of left atrial function.^[4][5]

The left atrium plays a vital role in modulating left ventricular filling through its reservoir, conduit, and booster pump functions. These phases are sequentially influenced by LV systolic function, ventricular compliance, and diastolic pressures. LA strain, derived from 2D-STE, is measured during the reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct). Among these, reservoir strain (LASr) has been identified as a particularly robust index for detecting elevated LV filling pressures and early diastolic dysfunction.^[6]

Aim

To evaluate left atrial strain as a predictor of diastolic dysfunction in patients undergoing echocardiographic assessment.

Objectives

1. To measure left atrial strain using two-dimensional speckle-tracking echocardiography in study participants.
2. To assess diastolic function using conventional echocardiographic parameters as per ASE/EACVI 2016 guidelines.
3. To correlate left atrial strain values with the severity of diastolic dysfunction.

Source of Data: The study population comprised patients referred for routine transthoracic echocardiographic evaluation at the Department of Cardiology, who fulfilled the eligibility criteria. Data were obtained from consecutive patients after obtaining informed written consent.

Study Design: Cross-sectional observational study.

Study Location: Department of Cardiology at tertiary care hospital.

Study Duration: January 2023 to March 2024.

Sample Size: 120 patients.

Inclusion Criteria

• Adult patients aged ≥18 years.
• Patients with sinus rhythm at the time of echocardiographic evaluation.
• Preserved left ventricular ejection fraction (≥50%).
• Patients providing informed consent.

Exclusion Criteria

• Poor echocardiographic window precluding adequate image acquisition.
• Significant valvular heart disease (moderate to severe stenosis or regurgitation).
• History of atrial fibrillation or other sustained arrhythmias.
• Presence of congenital heart disease.
• Prior cardiac surgery or intervention affecting LA or LV geometry.
• Acute coronary syndrome within the preceding 3 months.

Procedure and Methodology

All participants underwent standard transthoracic echocardiography (TTE) using commercially available echocardiography equipment with a phased-array transducer (2–4 MHz).

Standard Echocardiographic Assessment: Left ventricular ejection fraction (LVEF) was calculated using the modified Simpson’s biplane method. Diastolic function was assessed according to ASE/EACVI 2016 guidelines using:

Mitral inflow velocities (E wave, A wave, E/A ratio) from pulsed-wave Doppler at the mitral leaflet tips in the apical four-chamber view.

Tissue Doppler imaging (septal and lateral e′ velocities).

E/e′ ratio (average of septal and lateral values).

Tricuspid regurgitation velocity by continuous-wave Doppler.

Left atrial volume indexed to body surface area (LAVI), measured using the biplane area-length method.

Left Atrial Strain Measurement: Two-dimensional speckle-tracking echocardiography was performed using the apical four-chamber view optimized for the LA, with a frame rate between 50–70 frames per second. The LA endocardial border was manually traced at end-systole, excluding pulmonary veins and the LA appendage. The software automatically generated a region of interest (ROI) covering the LA myocardium, which was adjusted if necessary for optimal tracking. LA strain curves were derived, and the peak reservoir strain (LASr) during ventricular systole was recorded. Additional conduit (LAScd) and contraction (LASct) strain values were noted where applicable. Three consecutive cardiac cycles were averaged for analysis.

Sample Processing

All echocardiographic images were digitally stored and analyzed offline using vendor-specific software. Image analysis was performed by two independent echocardiographers blinded to the patients’ clinical details to minimize inter-observer variability.

Statistical Methods

Data were entered into Microsoft Excel and analyzed using SPSS software (version 27). Continuous variables were expressed as mean ± standard deviation (SD) and compared using Student’s t-test or ANOVA, as appropriate. Categorical variables were presented as frequencies and percentages, and compared using Chi-square test or Fisher’s exact test. Pearson’s or Spearman’s correlation coefficients were calculated to assess the relationship between LA strain and diastolic function parameters. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the optimal LA strain cut-off for predicting diastolic dysfunction. A p-value <0.05 was considered statistically significant.

Data Collection

Patient demographics, clinical history, cardiovascular risk factors, and echocardiographic parameters were recorded in a pre-designed case record form. All data were anonymized, coded, and stored securely with restricted access to maintain confidentiality.

Table 1: Evaluate left atrial strain (LASr) as a predictor of diastolic dysfunction (DD)

DD present: n=52 DD absent: n=68 Total: N=120

Notes: Mean difference reported as (Present − Absent). OR = odds ratio for DD (Present vs Absent).

Table 1 presents the comparison of baseline characteristics and left atrial strain values between patients with and without diastolic dysfunction (DD). Patients with DD (n=52) were significantly older, with a mean age of 58.9 ± 10.4 years, compared to 53.1 ± 11.2 years in those without DD (p=0.004, 95% CI: 1.88–9.72). The proportion of females was similar in both groups (40.4% vs 41.2%, p=0.930). Hypertension was significantly more common among DD patients (67.3%) compared to non-DD patients (42.6%), with an odds ratio (OR) of 2.77 (95% CI: 1.30–5.88, p=0.007). Diabetes mellitus prevalence was also higher in the DD group (46.2% vs 26.5%, OR=2.38, 95% CI: 1.11–5.12, p=0.025). BMI was slightly higher in the DD group (28.1 ± 4.1 vs 26.8 ± 3.7 kg/m²), but this difference did not reach statistical significance (p=0.076). Left atrial reservoir strain (LASr) was markedly reduced in DD patients (21.6 ± 5.4%) compared to those without DD (37.8 ± 6.2%), with a highly significant difference (p<0.001, 95% CI: −18.30 to −14.10). Additionally, a LASr value below 24% was observed in 73.1% of DD patients versus only 10.3% in non-DD patients (OR=23.65, 95% CI: 8.76–63.89, p<0.001), indicating strong predictive capability.

Table 2. Measurement of left atrial strain by 2D-speckle tracking (distribution and sex comparison)

Table 2 shows the distribution of left atrial strain parameters measured by 2D-speckle tracking and their comparison between males and females. The mean reservoir strain (LASr) in the overall population was 31.8 ± 9.9%, with no significant sex difference (31.2 ± 10.3% in males vs 32.6 ± 9.4% in females, p=0.561). Similarly, conduit strain (LAScd) and contraction strain (LASct) were comparable between groups, with mean values of 18.2 ± 6.1% and 11.6 ± 4.0%, respectively, and no statistically significant differences (p>0.4 for both). Adequate LA tracking quality was achieved in more than 92% of both sexes, again without significant variation (p=0.682).

Table 3: Conventional diastolic parameters (ASE/EACVI 2016) by diastolic dysfunction status

DD present: n=52 DD absent: n=68

Table 3 compares conventional echocardiographic diastolic function parameters between patients with and without DD, based on ASE/EACVI 2016 criteria. DD patients exhibited significantly lower mitral E/A ratio (0.85 ± 0.27 vs 1.12 ± 0.31, p<0.001), reduced septal e′ (6.1 ± 1.4 vs 8.2 ± 1.6 cm/s, p<0.001), and lateral e′ velocities (8.4 ± 1.8 vs 10.9 ± 2.0 cm/s, p<0.001). They also had higher average E/e′ ratio (15.7 ± 3.0 vs 9.8 ± 2.1, p<0.001), increased tricuspid regurgitation velocity (2.79 ± 0.41 vs 2.41 ± 0.31 m/s, p<0.001), and larger left atrial volume index (LAVI) (36.8 ± 7.2 vs 28.9 ± 5.8 mL/m², p<0.001). Left ventricular ejection fraction (LVEF) was similar between groups (p=0.260), consistent with preserved systolic function in diastolic dysfunction.

Table 4: Correlation of left atrial reservoir strain (LASr) with diastolic dysfunction severity

Severity categories: Normal (Grade 0), Grade I, Grade II, Grade III

Table 4 explores the correlation between LASr and the severity of diastolic dysfunction, classified into normal (Grade 0) and Grades I–III. Mean LASr declined progressively with increasing severity: 38.1 ± 6.0% in Grade 0, 26.7 ± 5.1% in Grade I, 19.8 ± 4.6% in Grade II, and 13.9 ± 3.8% in Grade III. The one-way ANOVA revealed a highly significant difference across all grades (p<0.001), with a strong negative correlation between LASr and DD severity (Spearman’s ρ=−0.82, 95% CI: −0.87 to −0.74). Pairwise comparisons confirmed that LASr was significantly lower in each increasing grade of dysfunction compared to normal subjects, highlighting its potential as a gradation marker for diastolic impairment.

Table 1 (LASr as a predictor of DD). Data show a large separation in LA reservoir strain (LASr) between DD and non-DD groups (21.6 ± 5.4% vs 37.8 ± 6.2%; p<0.001), while classic risk factors such as hypertension (67.3% vs 42.6%) and diabetes (46.2% vs 26.5%) were more prevalent in DD. This pattern mirrors guideline pathophysiology in which chronically elevated LV filling pressures drive LA remodeling and functional impairment; the 2016 ASE/EACVI document highlights higher E/e′ and increased LAVI as markers of DD and explains why LA function deteriorates as filling pressures rise. non-DD LASr mean (≈38%) aligns closely with Nishida G et al.(2023)^[7] meta-analytic “normal” for reservoir strain (~39%), supporting internal validity of cohort’s reference values. Finally, the older age in DD (mean difference +5.8 years) and clustering of hypertension/diabetes are consistent with the comorbidity profile seen in HFpEF populations where LA dysfunction is prominent and prognostically relevant. Brand A et al.(2023)^[8]

A particularly compelling finding is LASr <24% threshold (OR = 23.65) for DD. Literature suggests cut-offs vary by population, EF status, and vendor, typically spanning the high-teens to mid-20s. Thomas L et al.(2019)[9] demonstrated that LASr stratifies ASE/EACVI DD grades with strong diagnostic performance in preserved EF, while Nagueh (2023) and contemporary mechanistic work report high specificity around ≤18% for elevated LV filling pressures—especially when EF is reduced; in preserved EF cohorts, slightly higher thresholds (≈20–24%) improve sensitivity at the cost of specificity. 24% rule-in/rule-out behavior therefore sits within the published range (≈17–24%) and reflects a reasonable balance for a general echo population. Xu Y et al.(2024)^[10]

Table 2 (LA strain measurement and sex comparison): In the study cohort of 120 participants, mean left atrial reservoir strain (LASr) was 31.8 ± 9.9%, with no significant sex-related differences (males: 31.2 ± 10.3%, females: 32.6 ± 9.4%, p=0.561). Conduit strain (LAScd) and contraction strain (LASct) were also similar between sexes (18.2 ± 6.1% overall; 17.9 ± 6.3% in males vs 18.6 ± 5.8% in females, p=0.486; and 11.6 ± 4.0% overall; 11.3 ± 4.1% in males vs 12.0 ± 3.8% in females, p=0.441, respectively). Adequate LA tracking was feasible in >92% of cases for both sexes. These findings align with prior meta-analytic evidence showing minimal demographic impact on LA strain when imaging quality and rhythm are standardized, consistent with EACVI/ASE/Industry consensus recommendations (Hatipoglu S et al., 2014)^[11].

Table 3 (Conventional diastolic indices vs DD). The DD group demonstrates the canonical diastolic profile: lower E/A and e′ velocities, higher E/e′ and TR velocity, and larger LAVI—all with large, statistically robust differences—while LVEF remains preserved, as anticipated in many DD/HFpEF patients. This pattern tracks closely with ASE/EACVI criteria for grading diastolic function and estimating LA pressure. Importantly, studies have shown that adding LA strain to LAVI improves diagnostic yield and reclassification, especially when conventional parameters conflict or yield “indeterminate” grades. dataset reflects that paradigm: LASr powerfully discriminates DD beyond the volumetric marker (LAVI). Singh A et al.(2017)^[12]

Table 4 (LASr vs severity of DD). LASr falls stepwise from normal to Grade III (38.1% → 26.7% → 19.8% → 13.9%), with a strong inverse correlation to severity. This mirrors Kim M et al.(2023)^[13], who showed monotonic LASr decline across ASE/EACVI grades and supported LASr-based categorization. More recent work demonstrates that incorporating LASr reduces “indeterminate” classifications and tracks invasive filling pressures better than LAVI, bolstering the case for its integration as a tie-breaker when standard indices disagree-exactly the clinical niche results support. Esposito R et al.(2016)[14]

This cross-sectional echocardiographic study demonstrates that left atrial reservoir strain (LASr), measured by two-dimensional speckle-tracking, is a robust, non-invasive predictor of diastolic dysfunction in patients with preserved ejection fraction. LASr values were significantly reduced in subjects with diastolic dysfunction and showed a strong, graded inverse relationship with severity of dysfunction. A cut-off value of <24% was highly predictive of diastolic dysfunction, complementing and enhancing the diagnostic accuracy of conventional echocardiographic parameters recommended by ASE/EACVI guidelines. These findings support the integration of LASr into routine diastolic function assessment protocols to improve early detection and grading, especially in patients with risk factors such as hypertension and diabetes.

LIMITATIONS OF THE STUDY

1. Cross-sectional design: Causal relationships between LASr and clinical outcomes could not be established.
2. Single-center setting: Limits generalizability to other populations and practice environments.
3. Vendor-specific software: Strain values may vary with different echocardiographic platforms and algorithms.
4. Preserved EF cohort only: Findings may not directly apply to patients with reduced ejection fraction or atrial fibrillation.
5. Exclusion of poor imaging windows: May have introduced selection bias by excluding patients with suboptimal echocardiographic quality.
6. Lack of invasive hemodynamic validation: LASr was not correlated with direct measurements of left ventricular filling pressures.
7. Relatively small sample size for severe DD: Few Grade III cases may limit accuracy of cut-off determination in advanced disease stages.

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