Myocardial steatosis impairs left ventricular diastolic-systolic coupling in healthy humans.

Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48-hour food restriction model to acutely increase myocardial triglyceride (mTG) content - measured by 1 H magnetic resonance spectroscopy - in 27 young healthy volunteers (13 men/14 women). Forty-eight hours of fasting caused a more than 3-fold increase in mTG content (p < 0.001). Diastolic function - defined as early diastolic circumferential strain rate (CSRd) - was unchanged following the 48-hour fasting intervention, but systolic circumferential strain rate was elevated (p < 0.001), indicative of systolic-diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low-dose dobutamine (2 μg/kg/min) caused a similar change in CSRs as was found during 48-hour of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic-systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. KEY POINTS: Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48-hour food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target. Abstract figure legend Acute elevations in myocardial triglyceride content impairs left ventricular diastolic-systolic coupling. Fasting for 48 hours causes a robust increase in circulating free fatty acids (FFA), which leads to an acute increase in myocardial triglyceride content (termed 'cardiac steatosis'), along with diastolic-systolic uncoupling. This article is protected by copyright. All rights reserved.