Prognostic Implications of Elevated Left Ventricular Ejection Fraction in Patients with Sepsis

Summary

This study evaluates sepsis patients at Beth Israel Deaconess Medical Center to determine whether elevated left ventricular ejection fraction predicts 28-day mortality.

Abstract

The role of left ventricular systolic function as a prognostic marker for sepsis patients remains an area of ongoing research and debate. The present investigation exhibited the comprehensive evaluation of the relationship between different levels of left ventricular ejection fraction (LVEF) and mortality outcomes in sepsis-diagnosed patients. A retrospective, single-center longitudinal cohort investigation was conducted involving the intensive care unit (ICU) admitted adults' patients at Beth Israel Deaconess Medical Center who underwent transthoracic echocardiography (TTE) during their hospitalization. Individuals diagnosed with sepsis and who received Doppler echocardiography were included in the analysis if transthoracic echocardiography was performed within seven days of ICU admission. All patients of age below 18 or above 90 years, a prior history of cardiac disease or cardiac surgery, and those for whom echocardiography was performed more than seven days after ICU admission were excluded. Patients were stratified into three distinct groups with relation to their LVEF levels: hyperdynamic (LVEF ≥70%), normal (LVEF 55%-70%), and depressed (LVEF ≤55%). The association between different categories of sepsis affected patients mortality outcome and left ventricular ejection fraction (LVEF) was assessed. Among the 3,363 patients analyzed, comprising 1,175 with decreased LVEF, 2,119 with normal LVEF, and 68 with hyperdynamic LVEF, multivariate Cox regression identified hyperdynamic function as the strongest predictor of 28-day mortality. Specifically, hyperdynamic LVEF was independently linked to a 3.643-fold higher hazard of death relative to the normal LVEF group. A significant link has been identified between hyperdynamic left ventricular function and elevated 28-day mortality rates in the ICU-admitted septic patients. This physiological condition underscores the need for enhanced clinical awareness due to its prognostic significance.

Introduction

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection¹. Among the organs affected, the heart is particularly susceptible. The reversible myocardial dysfunction that arises during sepsis, in the absence of underlying ischemic heart disease or pre-existing cardiac conditions, is referred to clinically as septic cardiomyopathy (SCM). The reported incidence of septic cardiomyopathy varies widely, ranging from 10% to 70%^2,3.

An important clinical inquiry persists: to what extent does septic cardiomyopathy impact the prognosis of individuals diagnosed with sepsis? Several studies have attempted to address this issue; however, the underlying pathophysiological mechanisms of SCM remain incompletely understood, and a universally accepted definition is still lacking^4,5,6,7. This lack of standardization contributes to inconsistencies in related research findings⁸. Recent molecular analyses also highlight the involvement of regulated cell death pathways and immune infiltration in cardiac dysfunction, suggesting that inflammatory signaling may play a broader role in myocardial impairment under critical illness conditions⁹.

In routine clinical settings, echocardiography serves as the principal method for evaluating septic cardiomyopathy because it is widely available, non-invasive, and allows for repeated assessments. Cardiac function is typically evaluated using various parameters, including stroke volume, cardiac output, and particularly left ventricular ejection fraction (LVEF), which is widely recognized as the standard measure of left ventricular systolic performance¹⁰. Although advanced imaging modalities such as speckle-tracking strain echocardiography and tissue Doppler imaging provide additional insight into myocardial mechanics, LVEF remains the most widely used and clinically accessible measure of systolic function in the ICU setting. Biomarkers such as BNP or troponin may support assessment but lack the immediate hemodynamic relevance that echocardiography offers^9,11.

A considerable number of septic patients exhibit abnormalities in LVEF on color Doppler echocardiography, encompassing both decreased and excessively elevated values. Some prior studies have suggested a link between abnormal LVEF especially hyperdynamic LVEF (greater than 70%) and increased mortality among sepsis patients¹². Recent advances in molecular cardiology have emphasized the need for improved diagnostic markers and mechanistic insights to better stratify cardiovascular risk across diverse pathological states¹³. However, these findings remain inconclusive, with other investigations reporting contradictory results^{6,13,14,15,16,17,18}. Given these unresolved questions, A retrospective investigation was undertaken to investigate the correlation between left ventricular ejection fraction and clinical outcomes of the septic patients.

Protocol

The study was conducted using de-identified patient data from the MIMIC-IV database (version 2.2). Approval for use of this dataset was granted by the Institutional Review Board of the Beth Israel Deaconess Medical Center, with a waiver of informed consent due to the anonymized nature of the data. Access to the database was authorized under certification number 60177335. The equipment used is listed in the Table of Materials.

1. Data source

The MIMIC-IV (version 2.2) database was accessed through the PhysioNet platform after completion of the required training. Clinical, laboratory, ICU, and echocardiographic data were retrieved for patients admitted to Beth Israel Deaconess Medical Center from 2008-2019. All downloaded datasets were stored in a secure research environment in accordance with PhysioNet and institutional policies.

2. Patient selection

All ICU-admitted adult patients aged 18-90 years within the dataset were identified. Sepsis was defined according to Sepsis-3 criteria, requiring suspected infection and an acute increase in SOFA score ≥2. Patients who underwent transthoracic echocardiography (TTE) within 7 days of ICU admission were included. Exclusion criteria were applied for patients younger than 18 or older than 90 years, those with a documented history of cardiovascular disease or previous cardiac surgery, and those whose TTE was performed more than 7 days after ICU admission. Demographic and clinical characteristics, including age, sex, height, weight, vital signs, comorbidities, laboratory findings, and the use of vasoactive medications, were extracted. Severity scores, including SOFA and APACHE, were also obtained, along with ICU length of stay and total hospital stay. Only the first ICU admission for each patient was included in the analysis.

3. LVEF measurement and classification

Left ventricular ejection fraction (LVEF) values were obtained from TTE reports. The biplane method of disks (modified Simpson's method) was used to determine end-diastolic volume (EDV) and end-systolic volume (ESV). LVEF was calculated using the formula: LVEF = [(EDV − ESV) / EDV] × 100%. Based on ACC guidelines, LVEF was categorized as reduced (<55%), normal (55%-70%), or hyperdynamic (>70%). Each patient was then assigned to one of the three LVEF groups for comparative analysis.

4. Statistical methods

All analyses were performed using R software (version 4.4.3). Categorical variables were presented as frequencies and percentages, and group comparisons were conducted using the chi-square test. Continuous variables were evaluated for normality using distribution plots. Non-normal continuous variables were reported as medians with interquartile ranges (IQRs), and differences between groups were assessed using the Kruskal-Wallis test. Univariate Cox proportional hazards regression was conducted to identify mortality-associated variables, and statistically significant predictors from the univariate analysis were included in multivariate Cox regression models to determine independent associations. The primary outcome was defined as 28-day mortality, and the secondary outcome as 1-year mortality. Survival analysis was performed using Kaplan-Meier curves stratified by LVEF group, and survival distributions were compared using the log-rank test. A two-sided p-value <0.05 was considered statistically significant.

Results

Baseline characteristics
As shown in Figure 1, the final analysis included 3,362 patients. Of these, 1,175 were categorized into the reduced LVEF group (≤55%), 2,119 had normal LVEF (55%-70%), and 68 patients demonstrated hyperdynamic LVEF (>70%). Table 1 presents the baseline demographic and clinical characteristics of the study population. The cohort had a median age of 69 years (IQR 60-77), and males represented 66% (n = 2,218) of the sample. When ...

Discussion

This study demonstrates a significant association between hyperdynamic left ventricular ejection fraction (LVEF) and increased 28-day mortality among septic patients admitted to the intensive care unit. This association remained consistent even after adjusting for confounding variables, underscoring the robustness of the findings. These results align with previously published work that has reported similar physiological patterns among patients with hyperdynamic ventricular function, including elevated cardiac output, inc...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Color Doppler Echocardiography unit	Siemens	Siemens Acuson X300 / X700 Series	Used to evaluate blood flow, cardiac hemodynamics, and support LVEF measurement
Transthoracic Echocardiography (TTE) System	Siemens	Siemens Acuson SC2000 PRIME	Used for cardiac ultrasound imaging; LVEF