Abstract 12273: Circulating Monocyte Mitochondrial Function Reflects Myocardial Oxidative Metabolism in Humans With Heart Failure

Abstract

Introduction: We previously showed that mitochondrial function in circulating monocytes is abnormal in humans with heart failure (HF) compared to normal controls, and that it correlates to cardiomyocyte mitochondrial function in dogs with HF. But, there is no data in humans supporting a relationship between monocyte mitochondrial function and cardiac energy metabolism. Hypothesis: To test the association of circulating monocyte mitochondrial function metrics with myocardial energy metabolism in patients with HF and reduced left ventricular (LV) ejection fraction (HFrEF) quantified using C 11 acetate PET imaging. Methods: We studied 10 patients with stable HFrEF that underwent the PET imaging. Region of interest analysis was used to yield time-activity curves that represent multiple LV myocardial regions. The early phase of tracer washout curves were fitted mono-exponentially to obtain the constant Kmono (a measure of oxidative metabolism). Peripheral blood monocytes were isolated and mitochondrial function was quantified using SEAHORSE. We tested the correlation of mitochondrial metrics with Kmono, adjusted for mechanical energetic output of the heart (calculated as stroke volume index*mean BP*heartrate). Results: Among the 10 patients (aged 57-74), 3 were women, 4 self-identified as Black, and 4 had ischemic etiology. Mean EF was 35% (range 18-45%), mean systolic BP was 126 (range 100-147), and mean Kmono was 0.054 (range 0.038-0.102). Results are summarized in the table. After accounting for variation in mechanical cardiac work, we found significant positive correlations of each mitochondrial metric with Kmono. Conclusions: We find that mitochondrial function in circulating blood monocytes may be a biomarker of cardiac oxidative metabolism and cardiomyocyte mitochondrial function. If validated as a non-invasive measure of cardiac energetics, this could accelerate research in cardiac energy deprivation and its relationship to HF progression.