Clinical value of ultrasound combined with diaphragmatic excursion assessment in evaluating right ventricular dysfunction in sepsis patients

Abstract

Background

Sepsis-induced myocardial injury often leads to right ventricular dysfunction (RVD), which worsens outcomes. Current RVD assessment methods are limited, and the role of diaphragmatic excursion (DE) remains understudied.

Objective

To evaluate the clinical utility of ultrasound combined with DE in assessing RVD in sepsis patients and validate its feasibility in primary care.

Methods

This retrospective study included 80 sepsis patients (40 RVD, 40 non-RVD) admitted from January 2022 to January 2025. Right ventricular dysfunction (RVD) was defined as meeting at least two of the following criteria: tricuspid annular plane systolic excursion (TAPSE) < 17 mm, right ventricular fractional area change (RVFAC) < 35%, or peak S’ wave velocity < 9.5 cm/s. Right ventricular function [DE, tricuspid annular plane systolic excursion (TAPSE), and right ventricular fractional area change (RVFAC)], inflammatory markers [procalcitonin (PCT), interleukin-6 (IL-6), lactate], and clinical outcomes were analyzed using correlation, regression, and receiver operating characteristic (ROC) curve analyses.

Results

The RVD group showed significantly lower DE, TAPSE, and RVFAC but higher IL-6, lactate, and PCT (P < 0.05). These patients required more mechanical ventilation and vasopressors, had longer ICU stays, and higher 28-day mortality (P < 0.05). DE correlated strongly with TAPSE (r = 0.655) and RVFAC (r = 0.612) (P < 0.001). Multivariate analysis identified DE (OR = 0.258) as independent RVD risk factors (P < 0.05). DE alone predicted RVD with an AUC of 0.885, while the combined model (DE+TAPSE+RVFAC) achieved an AUC of 0.990. Low DE was associated with poorer 28-day survival (P < 0.05).

Conclusion

Ultrasound combined with DE effectively assesses RVD in sepsis, with the combined model outperforming single parameters. This approach shows potential feasibility for primary care implementation with standardized protocols and targeted training.

Clinical trial registration

Not applicable.

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1, 2]. Myocardial injury is a severe complication, with right ventricular dysfunction (RVD) being particularly common and associated with poor outcomes. Lanspa et al. [3] reported that nearly half of sepsis patients exhibit RVD within 24 h of ICU admission, which is linked to a more than three-fold increase in 28-day mortality. Thus, early and accurate assessment of RVD in sepsis is clinically critical.

Echocardiography is the preferred method for evaluating right ventricular (RV) function due to its non-invasive nature, repeatability, and ease of use [4]. Guidelines from the American Society of Echocardiography recommend parameters such as tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) for routine assessment of RV systolic function [5]. These measures are valued for their simplicity and reproducibility in conditions like pulmonary hypertension and heart failure [6].

Meanwhile, clinical observations have found that the incidence of diaphragmatic dysfunction in sepsis patients in the intensive care unit exceeds 60% [7], became a significant cause of difficult weaning from mechanical ventilation, prolonged hospital stays, and increased mortality rates [8]. In recent years, with the deepening of molecular biology research, scholars have gradually uncovered the molecular mechanisms linking sepsis-induced diaphragmatic dysfunction to the suppression of myocardial contractile pathways [9]. Notably, the emergence of such energy metabolism disorders in the diaphragm often precedes clinical manifestations, suggesting that diaphragmatic function parameters may serve as early and sensitive biomarkers reflecting changes in right ventricular afterload. In clinical practice, ultrasound technology precisely enables the non-invasive and real-time synchronous acquisition of diaphragmatic mobility and right ventricular functional parameters [10]. This technological advantage not only provides a reliable tool for the joint assessment of right heart-diaphragm interactions in sepsis patients but also lays a solid theoretical foundation and technical feasibility for establishing an early warning system based on multi-parameter integration.

However, while ultrasound is established in cardiac assessment, the combined evaluation of DE and RV function in septic RVD remains underexplored, particularly regarding its feasibility in primary care settings. This study aims to investigate the clinical value of combining ultrasound parameters with DE for assessing RVD in sepsis patients and to validate its applicability in primary care.

Research methods

Subjects

This study is a retrospective clinical investigation. A total of 80 sepsis patients admitted to our hospital from January 2022 to January 2025 were included. Inclusion criteria were as follows: (1) meeting the diagnostic criteria for sepsis [11]; (2) aged between 18 and 65 years; (3) undergoing baseline ultrasound examination within 24 h after admission to the ICU. Exclusion criteria included: (1) a history of pre-existing cardiopulmonary diseases; (2) mechanical ventilation duration exceeding 48 h prior to the baseline ultrasound examination, in order to minimize the confounding effects of prolonged positive pressure ventilation on diaphragmatic function and right ventricular loading conditions; (3) severe hepatic or renal dysfunction; (4) inadequate quality of ultrasound images.

This clinical study adhered to relevant ethical guidelines, including the Declaration of Helsinki, and received approval from the hospital’s ethics committee prior to commencement. All participants involved in the study signed a comprehensive informed consent form. Throughout the research process, the privacy rights, right to information, and autonomy of the participants were fully safeguarded to ensure that the study protocol complied with medical ethical principles.

Grouping method

The patients were divided into the RVD group (n = 40) and the non-RVD group (n = 40) based on the occurrence of RVD. Grouping criteria: RVD group: Patients met at least two of the following criteria [12]: TAPSE < 17 mm; RVFAC < 35%; peak S’ wave velocity < 9.5 cm/s. Non-RVD group: All right ventricular parameters were normal.

Observation indicators

1. Diaphragmatic excursion (DE) [13]: A GE Vivid E9 color Doppler ultrasound diagnostic instrument with an ultrasound probe frequency of 3.5 MHz was used. During measurement, patients were required to be in a quiet state, avoiding interfering factors such as forceful breathing or coughing. The head of the patient’s bed was adjusted to an angle of 30° to 45°, and the patient was placed in a supine position. The probe was positioned between the mid-clavicular line and the anterior axillary line in B-mode, and observation was conducted through the hepatic and splenic acoustic windows to obtain the best imaging of diaphragmatic mobility. In B-mode, the diaphragm appeared as a bright line covering the liver or spleen, moving towards the probe during inspiration. Then, switching to M-mode ultrasound allowed for the detection of the diaphragm’s range of motion. The difference between the maximum and minimum distances of diaphragmatic movement during the same respiratory cycle was calculated as DE, and the mean value was taken after three repetitions. All ultrasound measurements, including DE, TAPSE, and RVFAC, were performed by two experienced attending physicians using a standardized measurement protocol, and both operators were blinded to the patients’ clinical data. To assess inter-observer variability, 20 randomly selected patients were re-evaluated by both physicians, and the intraclass correlation coefficient (ICC) was calculated. The ICC for all parameters was > 0.85, indicating excellent reproducibility.

Diaphragmatic dysfunction (DD) was defined as a DE of less than 1.00 cm [14].

• (2)Right ventricular (RV) function parameters: ① Measurement of TAPSE [15]: A GE Vivid E9 color Doppler ultrasound diagnostic instrument was used. Using M-mode transthoracic echocardiography in the four-chamber view, the M-mode cursor was directed to the junction of the RV lateral wall and the tricuspid valve (TV) plane. The maximum TAPSE was determined by the total displacement from the highest position of the tricuspid annulus after its atrial ascent to the peak descent during ventricular systole. ② RVFAC [16]: The apical four-chamber view was selected to measure the right ventricular end-diastolic area (RVEDA) and the right ventricular end-systolic area (RVESA). RVFAC=(RVEDA-RVESA) / RVEDA × 100%. The normal range for RVFAC is ≥ 35%.

• (3)Inflammatory markers: Peripheral venous blood samples were collected from patients after fasting. The levels of procalcitonin (PCT) and interleukin-6 (IL-6) were measured using a Roche cobas e602 fully automated electrochemiluminescence immunoassay analyzer. Lactate levels were measured using an LBGS-A10 arterial blood gas analyzer (Labtron Company).

• (4)Recording of clinical intervention measures: It was recorded whether patients received mechanical ventilation therapy and the duration of mechanical ventilation. Mechanical ventilation parameters were adjusted according to the patient’s specific condition, including tidal volume, respiratory rate, and fraction of inspired oxygen. It was also recorded whether patients received vasoactive drugs such as dopamine and norepinephrine. The doses of vasoactive drugs were adjusted based on the patient’s hemodynamic status and clinical manifestations to maintain effective circulatory perfusion and blood pressure.

• (5)Observation of prognostic indicators: Patients were followed up to observe and record prognostic indicators such as the length of ICU stay and 28-day all-cause mortality.

Statistical analysis

Data analysis was performed using SPSS 26.0 and R software. The normality of continuous variables was first assessed using the Shapiro-Wilk test. As all continuous variables were found to be normally distributed (P > 0.05), they were expressed as mean ± standard deviation, and comparisons between groups were conducted using independent-sample t-tests. Categorical variables, such as gender and mortality rate, were expressed as rates (%), and comparisons between groups were performed using the χ² test. Pearson correlation analysis was employed to explore the associations between DE and right ventricular function parameters as well as inflammatory markers.

A multivariate logistic regression analysis was used to identify factors associated with RVD. Before model construction, multicollinearity among independent variables was assessed using the Variance Inflation Factor (VIF), with a VIF < 5 considered acceptable. The linearity of continuous variables with the logit of the outcome was assessed using the Box-Tidwell test. The goodness-of-fit of the final logistic regression model was evaluated using the Hosmer-Lemeshow test. Initially, variables with P < 0.05 in the univariate analysis were candidates for the regression model. However, due to incorporation bias, TAPSE and RVFAC, which were part of the RVD definition, were excluded from the multivariate model.

The predictive performance of DE and the combined model of DE + TAPSE + RVFAC was compared using receiver operating characteristic (ROC) curves, with the area under the curve (AUC), sensitivity, and specificity calculated. The difference between the AUCs was formally compared using the DeLong test.

Patients were divided into low and high DE groups based on an optimal cutoff value derived from ROC analysis (9 mm) for survival analysis. Kaplan-Meier survival curves were plotted, and the log-rank test was used to compare 28-day survival between groups.

Results

Comparison of baseline data between RVD group and non-RVD group

Table 1 presents the baseline data of the two groups of patients. There were no significant differences between the RVD group and the non-RVD group in terms of gender, age, BMI, APACHE II score, SOFA score, underlying diseases, infection sites, and pathogen distribution (P > 0.05).

Table 1.

Baseline characteristics

Variables	RVD group (n = 40)	Non-RVD group (n = 40)	Effect size	P-value
Gender
Male	31 (77.50)	29 (72.50)	0.267	0.606
Female	9 (22.50)	11 (27.50)
Age (years)	49.23 ± 6.63	50.88 ± 5.29	1.230	0.222
BMI (kg/m2)	24.22 ± 1.38	24.67 ± 1.55	1.367	0.176
APACHE II (score)	22.43 ± 3.21	21.75 ± 3.09	0.958	0.341
SOFA (score)	9.35 ± 2.24	8.78 ± 2.42	1.103	0.274
Smoking history	24 (60.00)	25 (62.50)	0.053	0.818
Drinking history	26 (65.00)	23 (57.50)	0.474	0.491
Underlying diseases
Hypertension	15 (37.50)	13 (32.50)	0.220	0.639
Hyperlipidemia	9 (22.50)	10 (25.00)	0.069	0.793
Coronary heart disease	6 (15.00)	5 (12.50)	0.105	0.745
Diabetes	8 (20.00)	7 (17.50)	0.082	0.775
Temperature (℃)	37.22 ± 1.42	37.49 ± 1.35	0.861	0.392
Infection site
lung infection	21 (52.50)	17 (42.50)	0.802	0.371
Abdominal infection	31 (77.50)	29 (72.50)	0.267	0.606
Blood flow infection	6 (15.00)	8 (20.00)	0.346	0.556
Skin and soft tissue infections	3 (7.50)	4 (10.00)	0.000	> 0.99
Central nervous system infection	4 (10.00)	2 (5.00)	0.180	0.671
Infection site ≥ 2	22 (55.00)	18 (45.00)	0.800	0.371
Pathogen type
Klebsiella pneumoniae	15 (37.50)	14 (35.00)	0.054	0.816
Escherichia coli	13 (32.50)	12 (30.00)	0.058	0.809
Staphylococcus aureus	15 (37.50)	11 (27.50)	0.912	0.340
Acinetobacter baumannii	7 (17.50)	6 (15.00)	0.092	0.762
Pseudomonas aeruginosa	7 (17.50)	6 (15.00)	0.092	0.762
Pathogen types ≥ 2	13 (32.50)	9 (22.50)	1.003	0.317

Note: Data are presented as mean ± standard deviation or number (%). RVD: right ventricular dysfunction; BMI: body mass index; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment

Comparison of ultrasound parameters and inflammatory indexes between RVD group and non-RVD group

The comparison of ultrasound parameters in Table 2 shows that patients in the RVD group had significantly lower DE (8.55 ± 1.65 mm vs. 12.08 ± 2.38 mm), TAPSE (15.00 ± 4.01 mm vs. 21.18 ± 1.55 mm), RVFAC (35.90 ± 4.38% vs. 42.88 ± 4.77%), and Peak S’ wave velocity (8.12 ± 1.15 cm/s vs. 11.02 ± 1.45 cm/s) compared to the non-RVD group (all P-values < 0.001).

Table 2.

Comparison of ultrasonic parameters and inflammatory indexes

Variables	RVD group (n = 40)	Non-RVD group (n = 40)	Effect size	P-value
DE (mm)	8.55 ± 1.65	12.08 ± 2.38	7.703	< 0.001
TAPSE (mm)	15.00 ± 4.01	21.18 ± 1.55	9.078	< 0.001
RVFAC (%)	35.90 ± 4.38	42.88 ± 4.77	6.811	< 0.001
Peak S’ wave velocity (cm/s)	8.12 ± 1.15	11.02 ± 1.45	9.961	< 0.001
IL-6 (pg/ml)	2111.15 ± 566.42	1562.43 ± 328.65	5.300	< 0.001
Lactate (mmol/L)	3.85 ± 1.02	2.96 ± 0.88	4.155	< 0.001
PCT (ng/ml)	14.45 ± 2.13	11.15 ± 1.68	7.712	< 0.001

Note: DE: diaphragmatic excursion; TAPSE: tricuspid annular plane systolic excursion; RVFAC: right ventricular fractional area change; IL-6: interleukin-6; PCT: procalcitonin

The comparison of inflammatory markers in Table 2 reveals that patients in the RVD group had significantly higher levels of IL-6 (2111.15 ± 566.42 pg/ml vs. 1562.43 ± 328.65 pg/ml), lactate (3.85 ± 1.02 mmol/L vs. 2.96 ± 0.88 mmol/L), and PCT (14.45 ± 2.13 ng/ml vs. 11.15 ± 1.68 ng/ml) compared to the non-RVD group (all P-values < 0.001).

Comparison of clinical intervention and prognostic indicators between the RVD group and the non-RVD group

The comparison of clinical interventions and prognoses in Table 3 shows that patients in the RVD group had significantly higher rates of mechanical ventilation usage (95.00% vs. 75.00%), vasoactive drug usage (92.50% vs. 72.50%), longer ICU stays (9.65 ± 1.53 days vs. 7.33 ± 1.25 days), and higher 28-day all-cause mortality (47.50% vs. 22.50%) compared to the non-RVD group (all P-values < 0.05).

Table 3.

Comparison of clinical intervention and prognostic indicators

Variables	RVD group (n = 40)	Non-RVD group (n = 40)	Effect size	P-value
Mechanical ventilation	38 (95.00)	30 (75.00)	6.275	0.012
Vasoactive drugs	37 (92.50)	29 (72.50)	5.541	0.019
Length of stay in ICU (d)	9.65 ± 1.53	7.33 ± 1.25	7.451	< 0.001
28-day all-cause mortality (%)	19 (47.50)	9 (22.50)	5.495	0.019

Note: Data are presented as mean ± standard deviation or number (%). ICU: intensive care unit

Pearson correlation analysis

The results of the Pearson correlation analysis in Table 4 show that RVD exhibits a significant negative correlation with DE (r=-0.657), TAPSE (r=-0.717), and RVFAC (r=-0.611) (all P-values < 0.001). Meanwhile, DE demonstrates a significant positive correlation with TAPSE (r = 0.655) and RVFAC (r = 0.612) (both P-values < 0.001).

Table 4.

Pearson correlation analysis

	RVD*DE	RVD*TAPSE	RVD*RVFAC	DE*TAPSE	DE*RVFAC
Pearson r	-0.657	-0.717	-0.611	0.655	0.612
P	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

Note: RVD: right ventricular dysfunction; DE: diaphragmatic excursion; TAPSE: tricuspid annular plane systolic excursion; RVFAC: right ventricular fractional area change

Multivariate logistic regression analysis

A multivariate logistic regression analysis was conducted to identify factors independently associated with RVD. After testing for multicollinearity, all included variables showed a VIF of less than 2, indicating no significant multicollinearity. The Box-Tidwell test confirmed the linearity of the continuous variables with the logit (P > 0.05). To avoid incorporation bias, TAPSE and RVFAC, which were components of the RVD definition, were excluded from the multivariate model. The final model, presented in Table 5, identified DE as an independent factor associated with RVD after adjustment for candidate variables entered the multivariate analysis. Results revealed that DE (OR = 0.258, 95% CI: 0.100-0.667, P = 0.005) remained an independent factor associated with the diagnosis of RVD in patients with sepsis. The Hosmer-Lemeshow test indicated a good fit for the model (χ²=2.894, P = 0.941).

Table 5.

Multivariate logistic regression analysis

	B	Standard error	Z	OR	P-value	95% CI
DE	-1.355	0.485	-2.796	0.258	0.005	0.100-0.667

Note: DE: diaphragmatic excursion; OR: odds ratio; CI: confidence interval

Predictive effectiveness comparison and Kaplan-Meier survival analysis

Figure 1-A show the results of the ROC curve analysis: DE (AUC = 0.885, 95% CI = 0.794–0.945; optimal cut-off value of 9 mm), TAPSE (AUC = 0.895, 95% CI = 0.807–0.953; optimal cut-off value of 16 mm), and RVFAC (AUC = 0.851, 95% CI = 0.753–0.920; optimal cut-off value of 35%) all exhibit good predictive value for RVD in patients with sepsis. Notably, the combined application of these three indicators demonstrates the best predictive performance (AUC = 0.990, sensitivity of 95.00%, specificity of 100.00%). A formal comparison of the ROC curves using the DeLong test confirmed that the combined model performed significantly better than DE alone (Z = 3.034, P = 0.002).

Fig. 1.

(A) ROC curve of DE+TAPSE+RVFAC for predicting RVD in septic patients; (B) Comparison of survival rate between High DE group and Low DE group

Based on the ROC-derived optimal cutoff value of 9 mm, patients were divided into low DE (< 9 mm) and high DE (≥ 9 mm) groups. Kaplan-Meier survival analysis revealed that the 28-day survival rate was significantly lower in the low DE group (Log Rank χ²=6.542, P = 0.011). See Fig. 1B.

Discussion

RV dysfunction is common in septic patients and can worsen outcomes by impairing hemodynamics, triggering pulmonary circulation disorders, and exacerbating hypoxemia. Early identification of RV dysfunction is therefore crucial for improving prognosis. This retrospective study analyzes clinical data from 80 septic patients to evaluate the utility of combined ultrasound and DE assessment for RV dysfunction.

The diaphragm, as the primary respiratory muscle, has a functional state closely related to respiratory function and also exhibits complex interactions with the cardiovascular system [17]. This study found that in patients with sepsis-induced RVD, DE was significantly reduced, and DE showed a significant positive correlation with TAPSE and RVFAC, suggesting a close association between DE and right ventricular function. This result provides a new perspective for understanding the mutual influence between respiratory and circulatory functions in patients with sepsis. This close association can be explained by several interconnected pathophysiological mechanisms that link diaphragmatic function to right ventricular performance. First, a mechanical and hemodynamic coupling exists. The diaphragm is the primary engine of respiration, and its contraction during inspiration creates negative intrathoracic pressure, which is the principal driver of venous return to the right heart [18]. When DE is reduced, this pressure gradient is diminished, leading to decreased systemic venous return and reduced preload for the right ventricle (RV). Over time, this chronic underfilling can contribute to RV systolic dysfunction [19]. Furthermore, the diaphragm’s influence on intrathoracic pressure also affects RV afterload; impaired diaphragmatic function can lead to inefficient breathing patterns and increased work of breathing, which may elevate intrathoracic pressure during expiration and impede RV outflow. Second, a systemic inflammatory crosstalk is critical in sepsis. The profound inflammatory response, characterized by elevated cytokines like IL-6 and PCT, does not target organs in isolation. These inflammatory mediators have been shown to directly depress myocardial contractility, including that of the RV [20]. Simultaneously, they induce diaphragmatic myofiber atrophy and contractile dysfunction through pathways involving oxidative stress and mitochondrial dysfunction, directly leading to reduced DE [21]. Thus, the inflammatory storm acts as a common upstream event, simultaneously impairing both the heart and the diaphragm. Third, diaphragmatic dysfunction can exacerbate RVD through hypoxia-induced pulmonary vasoconstriction. Ineffective diaphragmatic contraction can lead to regional alveolar hypoventilation and atelectasis, contributing to hypoxemia [22, 23]. Pulmonary vessels constrict in response to alveolar hypoxia (the Euler-Liljestrand mechanism) to match perfusion to ventilation. This vasoconstriction increases pulmonary vascular resistance, placing a significant afterload burden on the already vulnerable RV. In the septic patient, this increased afterload can rapidly precipitate or worsen RV failure. Therefore, reduced DE is not merely a parallel phenomenon but can actively contribute to RVD through mechanical, inflammatory, and hypoxic pathways, creating a vicious cycle that worsens patient outcomes. In addition, the observed association between reduced DE and RVD may also be influenced by mechanical ventilation, which can modify intrathoracic pressure, diaphragmatic motion, and RV loading conditions. Ventricular interdependence may further contribute to this relationship, as changes in RV pressure and geometry can affect biventricular filling and overall cardiopulmonary performance in septic patients.

In this study, patients with RVD showed significant reductions in ultrasound-measured parameters, including TAPSE, RVFAC, and S’ wave peak velocity, consistent with prior research [24]. TAPSE is measured using M-mode ultrasound to assess the displacement of the tricuspid annulus towards the apex during systole, primarily reflecting the longitudinal systolic function of the right ventricle. It is characterized by its simplicity of measurement and good reproducibility [25]. Under normal circumstances, a TAPSE value greater than 16 mm is considered normal, and a value less than 16 mm suggests RVD [26]. RVFAC is calculated by measuring the end-diastolic and end-systolic areas of the right ventricle using two-dimensional ultrasound and then determining the fractional area change, reflecting the overall systolic function of the right ventricle. Normally, an RVFAC value greater than 35% is considered normal [27]. However, the use of a single ultrasound parameter may have certain limitations in evaluating right ventricular function. For example, TAPSE primarily reflects the longitudinal systolic function of the right ventricle and may yield false-negative results when there is abnormal motion of the right ventricular free wall. The measurement of RVFAC is significantly influenced by the quality of the ultrasound section, and its accuracy may decrease when the right ventricle has an irregular shape. Therefore, combining multiple ultrasound parameters for assessment can improve the diagnostic accuracy of RVD.

One of the significant findings of this study is that DE is closely correlated with right ventricular function parameters and serves as an independent risk factor for the development of RVD in patients with sepsis, while also holding substantial predictive value for patient prognosis. As an important indicator reflecting diaphragmatic function, a decrease in DE not only suggests diaphragmatic dysfunction but may also indirectly indicate impaired right ventricular function. In this study, DE demonstrated a significant positive correlation with TAPSE and RVFAC, indicating that a reduction in DE occurs concurrently with a decline in right ventricular systolic function. Multivariate logistic regression analysis revealed an OR of 0.258 for DE, suggesting that decreased DE is an independent risk factor for the development of RVD in patients with sepsis. This finding provides a novel indicator for clinical assessment of right ventricular function. Additionally, ROC curve analysis showed that the AUC for DE alone in predicting RVD in patients with sepsis was 0.885, with a sensitivity of 75.00% and a specificity of 90.00%, indicating that DE has high predictive value. In terms of prognostic prediction, Kaplan-Meier survival analysis revealed that the 28-day survival rate was significantly lower in patients with low DE compared to those with high DE, suggesting that DE can serve as an important indicator for assessing the prognosis of patients with sepsis. Lecronier et al. [28] conducted a secondary analysis of two prospective observational studies, enrolling 92 mechanically ventilated patients grouped by the presence or absence of sepsis. The results showed that among the subgroup of patients who underwent ultrasound measurements, both septic and non-septic patients exhibited a decrease in end-expiratory diaphragmatic thickness. Patients with decreased or unchanged diaphragmatic function had a higher 28-day mortality rate. This finding underscores the critical role of diaphragmatic function in patient prognosis and supports the conclusions of this study. This may be because reduced DE reflects dual impairment in both respiratory and circulatory functions, which are the primary causes of death in patients with sepsis. Furthermore, decreased DE can lead to prolonged mechanical ventilation duration and extended ICU stays, thereby increasing the risk of infection and the incidence of complications, ultimately affecting prognosis. In this study, patients in the RVD group had a higher proportion of mechanical ventilation and vasoactive drug use, longer ICU stays, and a significantly higher 28-day all-cause mortality rate, further supporting this viewpoint.

This close association between DE and RV systolic parameters (TAPSE and RVFAC) raises an important physiological question: does reduced DE reflect a global impairment of the cardiorespiratory unit, potentially affecting the critical balance between RV contractility and afterload, known as RV-pulmonary artery (PA) coupling? The TAPSE/pulmonary artery systolic pressure (PASP) ratio has emerged as a valuable non-invasive surrogate for RV-PA coupling, offering prognostic insights beyond individual parameters in conditions characterized by increased afterload, such as septic shock [29, 30]. A declining TAPSE/PASP ratio indicates a mismatch where the RV is failing to adapt to the load imposed by the pulmonary circulation. Given the significant correlation between DE and TAPSE observed in our study, it is plausible that diaphragmatic dysfunction could influence RV-PA coupling. Ineffective diaphragmatic contraction can lead to hypoventilation and atelectasis, contributing to hypoxemia and subsequent pulmonary vasoconstriction (Euler-Liljestrand mechanism), thereby increasing right ventricular afterload. Simultaneously, the systemic inflammatory milieu in sepsis directly depresses myocardial contractility, including that of the RV. Therefore, a reduced DE might be a composite marker, signaling both an increased afterload (via hypoxic pulmonary vasoconstriction from poor ventilation) and a diminished contractile reserve. Future prospective studies should incorporate the measurement of PASP to calculate the TAPSE/PASP ratio, which would allow for a direct investigation of whether DE is an independent determinant of RV-PA uncoupling in septic patients.

This study demonstrates that a combined model incorporating DE, TAPSE, and RVFAC predicts RVD in septic patients with exceptional accuracy (AUC 0.990, sensitivity 95.00%, specificity 100.00%), significantly outperforming DE alone. This integrated ultrasound and DE approach enhances diagnostic precision by combining complementary assessments: TAPSE and RVFAC evaluate right ventricular systolic function, while DE reveals the relationship between respiratory and ventricular function, offering comprehensive clinical insights. Both methods are non-invasive, bedside-capable, and well-suited for dynamic monitoring in critically ill patients. Given the widespread availability of ultrasound, this approach may have potential applicability in primary care settings. In our study, reproducibility was excellent (ICC > 0.85), and all parameters were obtained using standardized protocols by experienced attending physicians, suggesting that reliable implementation may be achievable with targeted training. However, the feasibility of this approach in the hands of general practitioners was not directly evaluated in the current study.

Research limitations

This study has certain limitations. Firstly, as a retrospective study, it is subject to selection bias, which may affect the accuracy of the research findings. Future research could be conducted as prospective, multicenter studies to validate the reliability of the results obtained in this study. Secondly, the sample size was relatively small, with only 80 patients included, which may limit the generalizability of the conclusions. Subsequent studies should expand the sample size to enhance the persuasiveness of the research findings. Additionally, this study solely focused on the relationship between DE and RVD, without delving into the underlying pathophysiological mechanisms. Although we hypothesize that diaphragmatic dysfunction may influence right ventricular function by affecting intrathoracic pressure changes, direct evidence to support this assumption is lacking. Future research could incorporate animal experiments or more in-depth physiological studies to further elucidate the intrinsic connection between DE and RVD. Thirdly, and importantly, our study is subject to incorporation bias. The outcome variable, RVD, was defined using TAPSE and RVFAC. While we deliberately excluded these variables from the multivariate regression analysis to obtain unbiased estimates of association for DE, they were included alongside DE in the combined ROC model. This combined model (DE+TAPSE+RVFAC) should therefore be interpreted as a “composite diagnostic panel” reflecting routine clinical practice, rather than a true predictive model. The high diagnostic accuracy (AUC = 0.990) is likely influenced by this incorporation bias and requires external validation in an independent cohort where the outcome is defined by alternative methods or gold standards. In addition, RV-PA coupling could not be assessed in this study because PASP was not systematically collected and could not be reliably estimated in all patients from the archived echocardiographic data. Since calculation of the TAPSE/PASP ratio requires an adequately measurable tricuspid regurgitant jet, the absence of this information prevented us from evaluating afterload-adjusted RV function in the current cohort. Fourthly, the potential confounding effect of mechanical ventilation on our primary measurements must be considered. Patients in the RVD group had a significantly higher rate of mechanical ventilation. Positive pressure ventilation, especially with positive end-expiratory pressure (PEEP), can independently influence both RV function and DE. PEEP can decrease RV preload by reducing venous return and may increase RV afterload by compressing pulmonary vessels. Simultaneously, positive pressure can alter diaphragmatic position and its pattern of excursion, potentially biasing DE measurements. While our study excluded patients ventilated for > 48 h to mitigate prolonged effects, we did not collect or control for specific ventilator settings (e.g., PEEP level, tidal volume, mode of ventilation) at the time of the ultrasound examination. Therefore, we cannot statistically exclude the possibility that the observed differences in DE and RV parameters between the RVD and non-RVD groups were partially influenced by the ventilatory support itself, rather than solely by the underlying pathophysiological process. Future prospective studies should incorporate detailed ventilator parameters as covariates in multivariable models to more precisely delineate the independent relationship between diaphragmatic dysfunction and RVD in sepsis.

Conclusion

This study evaluated RVD in patients with sepsis by combining ultrasound assessment with DE measurement. It was found that DE, TAPSE, and RVFAC were independent risk factors for RVD, and the predictive performance of the combined model significantly outperformed that of the single parameter DE. This assessment method shows potential feasibility for primary healthcare settings and can provide novel insights and approaches for clinical practice. Larger-scale studies are needed in the future to validate these findings and explore their underlying pathophysiological mechanisms, providing more robust support for the early diagnosis and treatment of patients with sepsis.

Author contributions

Yu Sun: Collected and analyzed the data, wrote the drafting manuscript; Xuejing Liu and Yuting Bi: Investigation, wrote the drafting manuscript; Guokun Zhang: Designed the study, revised the manuscript. All authors have seen and approved the final, submitted version of this manuscript.

Funding

None.

Data availability

All data generated or analyzed in this study are included in the present manuscript.

Declarations

Ethics and informed consent

The study protocol was approved by the Ethics Committee of Hongqi Hospital Affiliated to Mudanjiang Medical University (Ethics Approval Number: 2025038). In accordance with the Declaration of Helsinki and the requirements of the Ethics Committee, all participants involved in the study signed a comprehensive informed consent form.

Competing interests

The authors declare no competing interests.