CT fatty muscle fraction as a new parameter for muscle quality assessment predicts outcome in venovenous extracorporeal membrane oxygenation

Abstract

Impaired skeletal muscle quality is a major risk factor for adverse outcomes in acute respiratory failure. However, conventional methods for skeletal muscle assessment are inapplicable in the critical care setting. This study aimed to determine the prognostic value of computed tomography (CT) fatty muscle fraction (FMF) as a biomarker of muscle quality in patients undergoing extracorporeal membrane oxygenation (ECMO). To calculate FMF, paraspinal skeletal muscle area was obtained from clinical CT and separated into areas of fatty and lean muscle based on densitometric thresholds. The cohort was binarized according to median FMF. Patients with high FMF displayed significantly increased 1-year mortality (72.7% versus 55.8%, P = 0.036) on Kaplan-Meier analysis. A multivariable logistic regression model was built to test the impact of FMF on outcome. FMF was identified as a significant predictor of 1-year mortality (hazard ratio per percent FMF, 1.017 [95% confidence interval, 1.002-1.033]; P = 0.031), independent of anthropometric characteristics, Charlson Comorbidity Index, Simplified Acute Physiology Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score, and duration of ECMO support. To conclude, FMF predicted 1-year mortality independently of established clinical prognosticators in ECMO patients and may have the potential to become a new muscle quality imaging biomarker, which is available from clinical CT.

Figure 1

Study inclusion flowchart. Patients who received venovenous ECMO for severe acute respiratory failure between December 2014 and August 2018 at our center were screened for eligibility (n = 306). Patients were excluded if no CT scan within 4 days of ECMO initiation was available (n = 176), if they received previous ECMO support (n = 22), or if CT scans were not applicable (n = 21). CT Computed tomography, ECMO Extracorporeal Membrane Oxygenation.

Figure 2

The concept of FMF. (A) Skeletal muscle fat infiltration is considered an indicator of muscle quality. Based on densitometric thresholds and accepted cut-off values of lean and fatty skeletal muscle, muscle compartments may be separated into areas of fatty and lean muscle. The FMF is calculated as the area of fatty muscle tissue related to the total skeletal muscle area, resulting in a relative and comparable measure of muscle quality. This biomarker can be opportunistically obtained from clinical CT scans. (B) Skeletal muscle area was obtained as the bilateral compartment area of paraspinal skeletal muscles at the level of the superior mesenteric artery. Within the skeletal muscle area, muscle tissue is identified by an attenuation threshold range of 100 to − 29 HU. Mean Radiodensity was highlighted to visualize overall muscle fat infiltration (myosteatosis). Based on thresholds ranges of − 29 to 29 HU for fatty muscle and 30 to 100 HU for lean muscle, FMF was calculated. CT Computed tomography, FMF Fatty muscle fraction, HU Hounsfield units.

Figure 3

Survival curve. Kaplan–Meier curve illustrating 1-year mortality of patients with high FMF compared to patients with low FMF. The entire study population (n = 87) was binarized based on median FMF with a cutoff value of > 44% to define high FMF. Patients with high FMF displayed significantly increased 1-year mortality following ECMO-implantation for acute respiratory failure (72.7% versus 55.8%, P = 0.036). ECMO Extracorporeal Membrane Oxygenation, FMF Fatty muscle fraction.

Figure 4

Exemplary patients. The paraspinal skeletal muscle area at the level of the superior mesenteric artery was separated into areas of fatty and lean muscle based on attenuation threshold ranges from CT scans around 4 days of ECMO implantation for acute respiratory failure. FMF was calculated at the fatty muscle area related to the total skeletal muscle area. Based on median FMF of the entire study population (n = 87), patients were binarized with a cutoff value of > 44% to define high FMF. Panels show exemplary patients with high and low FMF with corresponding 1-year mortality rates. CT computed tomography, ECMO Extracorporeal membrane oxygenation, FMF Fatty muscle fraction.