Elevated filling pressure (FP) contributes to dyspnoea and is central to heart failure (HF) pathogenesis (1). Accurate FP approximation is crucial for therapy optimisation and prognosis determination (2, 3). Cardiac catheterisation, the gold standard, is invasive and impractical for serial monitoring in all patients (4). Over the past three decades, extensive research has focused on a non-invasive, rapid, or bedside screening tool for FP assessment. The evaluation of left atrial (LA) pressure or pulmonary capillary wedge pressure, as opposed to left ventricular (LV) end-diastolic pressure, provides a more accurate reflection of the elevated FP (5, 6). This differentiation is essential as it ensures a more precise understanding of FP, as LV end-diastolic pressure primarily conveys information regarding LV compliance and preload. The current guidelines from the American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) advocate for the evaluation of mean left atrial (LA) pressure. This assessment involves a composite score derived from selected indices acquired through Doppler blood flow, tissue Doppler imaging, and LA volume measurements (7, 8). Recent data underscore that in patients falling into the indeterminate category, the inclusion of LA strain measurements can further enhance diagnostic accuracy (9, 10). Patients presenting suboptimal diagnostic image quality, atrial fibrillation, conduction abnormalities, and mitral annulus calcification pose challenges within the non-invasive assessment paradigm (11). Thus, the overall efficacy of the non-invasive approach in routine clinical settings remains challenging (12, 13). In our recent work, we used computed tomography images to demonstrate that patients with abnormal diastolic function, as determined by ASE/EACVI criteria and/or documented elevated LV end-diastolic pressure, exhibit a decrease in the ratio of LV-to-LA volume measured during diastasis, specifically below 1.40 (14). Therefore, we sought to test whether, in patients with dyspnoea and preserved LV ejection fraction (EF), transthoracic echocardiogram (TTE)-derived measurements of LV/LA volume ratio taken at predefined phases of the cardiac cycle, including the period of diastasis, could effectively estimate FP. To validate our findings, the TTE results were compared with measurements obtained from right and left heart catheterisation, including direct retrograde LA pressure.

Continuous variables are expressed as mean ± standard deviation, and categorical variables are expressed as numbers and percentages. The sample power for testing the hypothesis that there will be a difference in the LV/LA volume ratio between the two groups (with a significance level of ∝ < 0.05) was calculated to be 0.934 for the potential 50 patients based on data from the first 12 patients. An unpaired t-test, chi-square, or Fisher exact test was used, when appropriate, for comparison in clinical, echocardiographic, and haemodynamic data. Linear regression and Pearson correlation were used to assess the relationship between echocardiographic variables and FP. For the assessment of predictive accuracy in predicting elevated FP, logistic regression analysis with power analysis was used to determine the area under the curve. Univariate linear regression with Pearson correlation coefficients was used to evaluate the relationship between FP and various TTE variables, including LV/LA ratios. A multivariate analysis of covariance (MANOVA) with the D'Agostino–Pearson test for normal distribution was employed to conduct a comprehensive linear regression comparison between LV_dias/LA_dias and clinical variables, including FP. In addition, multivariate analysis of covariance was applied to examine the interdependence of TTE indices in assessing elevated FP. Receiver operating curve comparisons were performed by the DeLong et al. method (1988). Sensitivity and specificity were calculated in a standard manner. Intraobserver and interobserver variability in LV_dias, LA_dias, and the ratio of LV_dias/LA_dias were assessed using the Bland and Altman method [mean difference ±2 standard deviation, 95% confidence interval (CI)]. All tests were two-sided, with a value of P < 0.05 considered significant. All analyses were performed by JMP 15 (SAS Institute, Cary, NC, USA) and MedCalc version 22.009 (Ostend, Belgium).

The patients were divided into two groups: Group 1 consisted of 29 (55%) patients with elevated FP (with a mean LA pressure or pulmonary capillary wedge pressure of >12 mmHg), and Group 2 comprised 24 (45%) patients with normal FP (with a mean LA pressure or pulmonary capillary wedge pressure of ≤12 mmHg). Out of the entire cohort, direct LA pressure was measured in 44 (83%) patients, and in the remaining nine (17%) patients, the mean pulmonary capillary wedge pressure was analysed.

Table 1 presents the clinical characteristics of the study patients. No significant differences were observed in basic clinical characteristics, including age (Group 1 73 ± 9 years vs. Group 2 70 ± 11 years, P = 0.2666), gender, history of underlying hypertension, and/or type II diabetes. However, the body mass index was higher in Group 1 (30 ± 5 kg/m²) compared with that of Group 2 (26 ± 4 kg/m², P = 0.0057). The patients in Group 1 had a higher prevalence of stage 3 chronic kidney disease (52% vs. 17%, P = 0.006), elevated levels of N-terminal-prohormone of brain natriuretic peptide (902 ± 1,226 pg/ml vs. 294 ± 346 pg/ml; P = 0.0216), and a greater frequency of using loop and/or thiazides diuretics (41% vs. 17%; P = 0.0467). There were no significant differences observed in the use of other medications, but there was a tendency for a more frequent use of aldosterone antagonists and sodium-glucose transport protein 2-receptor inhibitors in Group 1 compared with Group 2. Furthermore, the patients in Group 1 exhibited lower levels of high-density lipids and tended to be more treated for obstructive sleep apnoea. The documented history of paroxysmal atrial fibrillation was similar in both groups (Group 1, 31% vs. Group 2, 25%; P = 0.2493), but all patients with chronic/persistent atrial fibrillation (7/53) were in Group 1 (P = 0.0058).

The average mean LA pressure and mean pulmonary capillary pressure were higher in Group 1 (19 ± 5 mmHg and 17 ± 5 mmHg, respectively) compared with Group 2 (9 ± 2 mmHg and 11 ± 3 mmHg, respectively), P < 0.0001 for all. Also, the peak of C-, V-, and A-waves of LA pressure, LV end-diastolic pressure, and mean pulmonary artery pressure were higher in Group 1 compared with Group 2. Between Group 1 and Group 2, there were no differences in pulmonary vascular resistance or transpulmonary pressure gradient (Table 2).

The agreement between LV_dias and LA_dias measurements was evaluated in a subgroup of 15 randomly chosen patients. This assessment aimed to determine the consistency or similarity between these two measurements. The mean difference between two independent observers (interobserver variability) was 0 ± 10 ml for LV_dias, −1 ± 10 ml for LA_dias, and 0.03 ± 0.32 for LV_dias/LA_dias. The mean difference between two measurements performed by the same operator (intraobserver variability) was 0 ± 13 ml for LV_dias, −1 ± 10 ml for LA_dias, and 0.04 ± 0.32 for LV_dias/LA_dias.

This prospective study involved a consecutive group of patients with persistent symptoms despite optimal medical therapy who subsequently underwent cardiac catheterisation. Our findings suggest that in individuals experiencing shortness of breath, lacking significant valve disease, and maintaining preserved LVEF, a non-invasive estimation of FP is possible using the LV/LA volume ratio obtained from standard two-dimensional TTE images.

Patients with elevated FP, defined by a mean LA pressure and/or pulmonary capillary wedge pressure higher than 12 mmHg, also displayed elevated LV end-diastolic pressure but not pulmonary vascular resistance or transpulmonary gradient (3–6). Consistent with existing literature, patients with elevated FP were characterised by a higher body mass index, elevated natriuretic peptide levels, a higher prevalence of chronic kidney disease, and a more frequent occurrence of persistent/chronic atrial fibrillation (18, 19).

Among all LV measurements, only the indexed LV stroke volume was shown to be reduced in patients with elevated FP, supporting the previously observed inverse relationship between LA pressure and LV stroke volume (20). The presence of increased LV wall thickness as well as concentric LV remodelling did not provide informative distinctions between patients with elevated and normal FP. These findings are also supported by previous studies, demonstrating that although LV hypertrophy is often present in patients with elevated FP, it is a non-specific finding (21).

Historically, LA_max measurement has been documented as a powerful predictor of survival following myocardial infarction (22). Recent research has linked an increase in LA_min to a poor prognosis in HF with preserved EF (23). We have observed that all measured LA volumes (LA_max, LA_dias, LA_min) were higher in patients with elevated FP. Differences were observed in LA reservoir function and LA pump function among the investigated LA function parameters, consistent with the findings reported by others (24). Notably, LA reservoir strain showed similar values in patients with normal and elevated FP, aligning with previous research indicating that LA reservoir strain is determined by LV strain (25) and has limited value in assessing FP in patients with preserved EF compared with those with reduced EF (10). The increase in LA volume throughout the cardiac cycle, measured at LA_max, LA_dias, and LA_min, and the observed impairment in LA reservoir function and strain observed in our study confirmed that the presence of atrial fibrillation contributes to LA remodelling.

Our data confirmed a well-documented inverse relationship between E/e' and FP (19, 26), but the combination of the scores recommended by ASE/EACVI provided limited assistance in distinguishing patients with elevated from normal FP (7). However, we did not evaluate the potential pathological increase in FP during exercise, which could reveal underlying diastolic dysfunction in some patients with normal resting FP (27).

The study showed a decrease in all three measured LV/LA volume ratios in patients with elevated FP. Among the TTE indices studied, the LV_dias/LA_dias ratio, with a cut-off value of ≤1.24 (for all patients, including those in atrial fibrillation) and ≤1.28 (for patients in sinus rhythm only) demonstrated the highest discriminatory ability for indicating elevated FP. This reduction in these LV/LA ratios correlated with the rate of increase in FP, as well as patients' age, as partially indicated in our previous work in patients with hypertension (28). A progressive reduction in the LV_dias/LA_dias ratio was observed in hypertensive heart disease and in patients with elevated resting FP, both in sinus rhythm and/or atrial fibrillation. This finding supports the potential clinical relevance of this ratio, with cut-off values of ≤1.62, ≤1.28, and ≤1.24, respectively, as illustrated in Figure 5.

The LV_dias/LA_dias ratio demonstrated superior performance compared with other TTE parameters, including LA_max index, LA reservoir function, LA reservoir strain, and LV stroke volume index. These findings underscore the potential utility of the LV_dias/LA_dias ratio in assessing elevated FP. The LV/LA volume ratios demonstrated ease of measurements and good reproducibility, offering an attractive alternative to the current complex assessment of FP, which often requires combined information from different imaging modalities. An additional benefit is its consistent accuracy, unaffected by the underlying rhythm, whether it in is sinus rhythm or atrial fibrillation.

The reduced LV/LA ratio can be explained by the impaired net atrio-ventricular compliance due to chronic LA myopathic remodelling, with the LA wall becoming thinner and more compliant compared with a thicker and less compliant LV wall resulting from chronically elevated preload (29). The concept of the LV-to-LA volume ratio has been explored previously. Spevack et al. (30) found that in patients with hypertension or diabetes, the ratio of LA to LV diameter can serve as a marker of the diastolic LV pressure–volume relationship. Their findings align with the findings of our present study exploring LV/LA volume ratios as potential indicators of elevated FP. Recent studies in cardiac magnetic resonance imaging, conducted by Pezel et al. (31), demonstrated that the LA to LV volume ratio (LA_min to LV_ED) could offer incremental prognostic value for predicting HF events beyond traditional risk factors. In addition, Garg et al. (32) suggested that elevated LV FP can be estimated from both LV mass and LA volume. Our study demonstrated a weak correlation between FP and either LV mass or LA_max acquired by TTE. It is important to note that we did not analyse any other cardiac imaging techniques, including cardiac magnetic imaging.

While our study involved a relatively small, consecutive group of patients, the inclusion of a small group of patients with chronic/persistent atrial fibrillation was intentional to address the diagnostic challenges posed by intrinsic atrial dysfunction, a key factor in HF (33, 34). We focused on patients with an LVEF cut-off value of ≥50%, and the potential role of LV/LA volume ratio indices in patients with reduced LVEF and/or valvular disease remains unknown. In addition, our cardiac catheterisation data were performed at rest, and potential exercise-related changes between FP and LV/LA volume ratio are unknown. The potential superiority of the proposed volumetric two-dimensional measurements, such as the LV_dias/LA_dias ratio, over other echocardiographic measurements, particularly LA strain, may be attributed to the inclusion of all examined patients without excluding them based on TTE image quality. Both LV and LA chamber volumes were manually traced by experienced sonographers, in contrast to the semiautomatic nature of obtaining LV or LA strain. This may explain the relatively lower accuracy of the LA strain, particularly in detecting elevated FP, as it was not limited to selected patients with good TTE image quality. Nevertheless, our study results indicate that the assessment of FP volume using the LV_dias/LA_dias ratio may be performed in essentially all patients, thereby providing a broader range of routine clinical applications.

Our study was performed on clinically stable patients. It is unknown whether our results could be incorporated in acute settings or in populations with significant valvular disease. Due to the fact that this was a single-centre study, further validation through a multicentre study should be considered.

This study suggests that in patients with dyspnoea and preserved LV ejection fraction, estimating FP is possible using the LV/LA volume ratio derived from routine TTE. The LV_dias/LA_dias ratio demonstrated the highest discriminatory ability to differentiate between patients with elevated FP and normal FP. The proposed measures of the LV/LA volume ratio, which can be easily obtained and replicated using routine TTE images, could provide an alternative approach to the current complex assessment of FP.