Load Incorporating Cardiac Assessment by Echocardiography In Patients With SEpsis (LIAISE Study)

Background Sepsis is a global killer, whereby an infection spreads throughout the body via the bloodstream. It often leads to lethal heart damage, "septic cardiomyopathy", with mortality rates for those affected soaring above 40%. To facilitate early and appropriate intervention for damaged hearts and improve their outcomes, accurate assessment of heart function, and proper prediction of their adverse events are crucial. However, conventional cardiac assessments cannot capture heart dysfunction accurately since they have a significant limitation called "load-dependency", which means these parameters' values are affected by loading conditions on the heart, such as blood pressure and circulating blood volume. In sepsis, as these loads on the heart dramatically change minute by minute, the values of cardiac assessment also fluctuate and frequently underestimates heart damage, failing to properly predict their adverse events. To address this, novel load-incorporating echocardiographic parameters can capture heart function more accurately regardless of these hemodynamic conditions, and previous data has demonstrated its better predictive value in cardiogenic shock cases where loading conditions similarly fluctuate. As a next step, this study seeks to elucidate their utility in patients with sepsis.

Aims

1. To investigate if novel load-incorporating echocardiography can predict adverse events more accurately than conventional parameters in adult patients with sepsis presenting to intensive care units (ICUs). 2. To identify the most sensitive cardiac parameter to predict adverse events in sepsis, from comprehensively collected cardiac parameters along with novel-incorporating echocardiography.

Hypothesis Load-incorporating echocardiographic parameters will be more accurate in predicting the incidence of adverse events within 30 days after ICU admission than conventional echocardiographic parameters.

Outcomes Primary outcome The incidence of all-cause death for 30 days after ICU admission

Secondary outcomes

* Incidence of and time to all-cause death or cardiovascular readmission for 1 year after ICU admission * Incidence and duration of mechanical circulatory support, mechanical ventilation, renal replacement therapy, and vasoactive agent therapy during initial admission. * Reversibility of cardiac function (LVEF increases ≥ 5% in echo 3-5 days after ICU admission) * Sequential Organ Failure Assessment (SOFA) score at 3 days after ICU admission

• All cause death and adverse cardiac event readmission [Time frame: 1 year after ICU admission]
• Mechanical circulartory suport, mechanical ventilation, renal replacement therapy, and vasoactive/inotropic agent therapy [Time frame: during the initial index admission, between Day 0 and Day 30]
• Reversibility of cardiac function [Time frame: Day 3 to Day 5]
• Sequential Organ Failure Assessment score at 3 days after ICU admission [Time frame: at Day 3 of ICU admission]