Abstract Body: Background: Left ventricular unloading with left ventricular assist devices (LVADs) induces reverse remodeling and myocardial recovery in a subset of patients with advanced heart failure (HF). Obesity is highly prevalent in HF and, despite its paradoxical association with improved survival in established HF, it remains unknown whether obesity modifies myocardial recovery following LVAD support and whether circulating sphingolipids (SLs), key regulators of cardiometabolic signaling, predict reverse remodeling.
Methods: HF patients (n=382) pre and post LVAD unloading were included to study the correlation of BMI and myocardial recovery. Patients were classified as responders (R, n=51) or non-responders (NR, n=331) based on functional and structural cardiac improvement after LVAD support. BMI (kg/m²) was recorded at implantation and phenotyping and divided into normal (18.5-24.9), overweight (25-29.9), class I obesity (30-34.9) and class II/III obesity (>35). Serum from a subset of patients collected at implantation underwent targeted liquid chromatography-based SL profiling and was correlated with BMI, and changes in EF and left ventricular end-diastolic diameter (LVEDD).
Results: At LVAD implantation, BMI distributions trended towards higher obesity prevalence among NR (35.7% vs 17.7%, p=0.08). Univariate analysis showed that every unit increase in baseline BMI was associated with a 9% lower likelihood of myocardial recovery (p= 0.005). After LVAD support, BMI distributions trended towards higher obesity prevalence in NR (p=0.09) but remained overall unchanged in R (p=0.29). Lipidomics showed that in HF patients with BMI>30, a higher circulating S1P-to-sphingosine ratio was associated with greater improvements in EF (β: 0.057, 95% CI: 0.013-0.100; p=0.012) and reductions in LVEDD (β: -0.002, 95% CI: -0.005 to -0.0002; p=0.036).
Conclusions: We found that obesity in advanced HF patients was associated with reduced probability of myocardial recovery following LVAD support. Serum levels of S1P/sphingosine ratio correlated with reverse remodeling post LVAD unloading in HF patients with BMI>30. The role of obesity and sphingolipid balance in recovery in advanced HF patients after LVAD support warrants further investigation in animal models.