Does Myocardial Steatosis Cause Left Ventricular Dysfunction

Altered substrate metabolism is thought to contribute to dysfunction of obese and diabetic hearts; however, the exact mechanism leading to dysfunction remains incompletely understood. One increasingly popular theory involves lipid overstorage (termed steatosis ) and lipotoxic injury to cardiomyocytes; however, these data have been derived almost entirely from pre‐clinical rodent models, with translational human research being far less developed; and often confounded by competing cardiovascular risk factors. Accordingly, we sought to study the acute influence of cardiac steatosis on cardiac function in otherwise healthy participants, using a unique 48‐hour fasting model. 7 young healthy men (24 ± 4 years)— free of cardiovascular, metabolic or neurological disease— volunteered for this study. Myocardial triglyceride content (mTG) was measured using 1 H magnetic resonance spectroscopy, and left ventricular function was measured using magnetic resonance imaging. Fasting was performed under the direct supervision of research nurses in the Clinical Research Unit (CRU) at the University of Texas Southwestern Medical Center. As expected, fasting for 48 hours caused mTG to increase in all participants (pre: 0.30 ± 0.14 % vs. post: 1.31 ± 0.93 %, p = 0.040). Despite multiple efforts to maintain cardiac preload during the fasting intervention, left ventricular end‐diastolic volume was significantly reduced (pre: 172.5 ± 22.7 mL vs. post: 155.7 ± 27.9 mL, p = 0.032) following the 48‐hour fast. Despite this marked reduction in cardiac preload, left ventricular peak strain and diastolic strain rate were preserved, while circumferential systolic strain rate (pre: −99 ± 11 %/s vs. post: −114 ± 5 %/s, p = 0.003), peak left ventricular twisting rate (pre: 47.8 ± 10.7 °/s vs. 71.0 ± 12.3 °/s, p = 0.012), and peak torsion (pre: 2.73 ± 0.58 °/cm vs. post: 3.36 ± 0.43 °/cm, p = 0.002) were all significantly elevated following the 48‐hour fast. We interpret these data to reflect heightened cardiac contractility, secondary to fasting induced activation of the sympathetic nervous system. Future studies are needed to test this hypothesis and control for this potential confounding variable, which may be otherwise masking steatosis induced cardiac dysfunction.