Small Pre-Implant LV Size Mediates Worse Post-Implant Outcomes in Female CF-LVAD Recipients

Abstract

<h3>Purpose</h3> Females have an increased risk of post-operative right ventricular failure (RVF) and early 3-month mortality after LVAD implantation, however the underlying mechanisms are unclear. We hypothesize that LV size-LVAD pump speed mismatch driven by smaller LVEDDs in females results in shifting of the interventricular septum (IVS), which contributes to the sex-differences in outcomes post-LVAD. <h3>Methods</h3> In this translational study, we utilized clinical and bench-top approaches. Adult CF-LVAD recipients from the ISHLT Mechanically Assisted Circulatory Support (IMACS) registry (n=15,498, Implant years: 2013-17, age: 56 + 13 yrs, 21% female) were studied to determine association of female sex with outcomes of 3-month post-implant mortality and RVF (RVAD/ >14 days post-LVAD inotropes), with and without LVEDD in the models. On the benchtop, four bi-ventricular patient-specific silicone heart phantoms (LVEDD = 6.1, 6.3, 8.1, 8.3 cm) were subjected to variable bi-ventricular loading states (Δ volume = LV volume - RV volume), while observing IVS position. <h3>Results</h3> There were 1,466 deaths (9.5%) within 3 months of implant, and 2,550 patients (16.5%) with RVF. Female sex was associated with 42% increased odds of 3-month mortality (p<0.001), and 18% increased odds of RVF (p=0.005) post-LVAD. Females had a smaller pre-implant LVEDD than males (6.49 ± 1.08 vs 6.93 ± 1.32 cm, p<0.001). Smaller LVEDD was independently predictive of worse outcomes after LVAD (adjusted OR per cm decrease in LVEDD for mortality: 1.20, p<0.001; RVF: 1.09, p<0.001). Addition of LVEDD to the regression models attenuated the effect size of female sex on 3-month mortality post-LVAD by 14% and RVF by 13%. In the phantoms, the IVSs of the two smaller hearts (blue) were abnormally shifted to the left at smaller Δ volume compared to the IVSs of the two larger hearts (orange) (Figure 1). <h3>Conclusion</h3> Smaller LV size partially mediates worse post-LVAD outcomes for female patients, due to lower Δ volume thresholds for leftward shift of the IVS in smaller hearts.