SPS9-04 End-Diastolic Volume in Septic Cardiomyopathy Is an Early Marker of Injury Severity and Survival

Background

Septic cardiomyopathy, a common sequalae of septic shock, is characterized by a reversible reduction in left ventricular ejection fraction (LVEF), yet this parameter has not correlated with the severity of cardiac injury, or risk of death.

Purpose

To determine pathophysiologic septic cardiomyopathy features that are indicators of injury severity and associated with outcome.

Data Sources

Three complementary septic shock sources were integrated 1) a cohort study of patients; 2) a canine model; and 3) a meta-analysis of clinical septic cardiomyopathy studies. One-hundred seventeen echocardiograms were analyzed from 103 subjects with septic shock admitted to the NIH ICU from 2000-2024. Purpose-bred beagles (n = 55) were studied with cardiac magnetic resonance imaging, arterial and pulmonary artery catheters, and electron microscopy (EM). Databases were searched from 1980-2025 to find septic cardiomyopathy studies characterizing function in survivors verses non-survivors.

Results

Unlike LVEF, the LV end-diastolic volume (LVEDV) was lower in septic patients surviving < 14-days, canines surviving < 5-days, and in non-survivors across 7 clinical septic cardiomyopathy studies (all p< 0.005). In septic patients, unlike LVEF, as LVEDV decreased the time to death decreased and the odds of dying increased, (both, P < 0.05). The LVEDV significantly decreased from baseline to 6h in non-surviving septic animals only. From 6-42h LVEDV increased in surviving septic animals to > 20% above baseline, while in non-survivors LVEDV increases only approached baseline (difference, p = 0.005). LVEDV decreases in septic animals at 6h were independent of cardiac loading conditions, reflecting more diastolic dysfunction, and associated with increased odds of dying (P < 0.05). Concurrently, in septic animals, LV wall percent water content increased, in non-survivors and survivors (both, p<0.004), which correlated with the LVEDV increases (combined, p = 0.0001). In survivors and non-survivors LV wall mass decreased (both P<0.006) but more so in non-survivors (p = 0.004). Degraded subcellular components were more prominent on EM in early deaths, than late deaths or survivors (both p < 0.05). Additionally, on EM, myocyte myofilament loss, edema and mitochondrial abnormalities —without inflammatory infiltrates — were greater in non-survivors versus survivors (all p < 0.05).

Conclusions

LVEDV is an easily assessable early metric associated with septic cardiomyopathy injury severity and outcome. We theorize the extracellular extrusion of degraded subcellular components mediates LV mass loss. The augmented LVEDV is due to the replacement of LV mass by water, increasing LV compliance. The lower LVEDV found in non-survivors is due to longitudinally injured cardiomyocytes, reducing diastolic function.

This abstract is funded by: US Government