Myocardial Sympathetic Innervation and Long-Term Left Ventricular Mechanical Unloading

ObjectivesThe purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart.BackgroundVentricular unloading by LVADs seems to cause reverse remodeling of the failing heart, but little is known about the sympathetic nerve activity during long-term mechanical unloading.MethodsWe studied the effects of LVADs on myocardial sympathetic innervation, by iodine 123-meta-iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1) heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic measurements were made 3 months apart in 6 other heart failure patients not treated with an LVAD.ResultsAfter 3 months of LVAD support, the mean left ventricular ejection fraction had increased from 19 ± 6% to 29 ± 9% (p = 0.006), peak oxygen consumption increased from 9 ± 4 ml/kg/min to 13 ± 3 ml/kg/min (p = 0.058), serum sodium increased from 135 ± 4 mEq/l to 140 ± 2 mEq/l (p = 0.014), whereas the left ventricular end-diastolic diameter decreased from 72 ± 7 mm to 56 ± 3 mm (p = 0.002), pulmonary capillary wedge pressure decreased from 30 ± 6 mm Hg to 5 ± 3 mm Hg (p = 0.012), serum creatinine decreased from 1.5 ± 0.6 mg/dl to 1.0 ± 0.4 mg/dl (p = 0.011), and B-type natriuretic peptide decreased from 2,279 ± 1,900 pg/ml to 102 ± 5 pg/ml (p = 0.003). After 3 months of LVAD, the H/M ratio increased on delayed images from 1.25 ± 0.18 to 1.43 ± 0.13 (p = 0.01) and on early images from 1.35 ± 0.19 to 1.44 ± 0.11 (p = 0.028), and the washout rate decreased from 51.0 ± 23.2% to 30.6 ± 8.7%, (p = 0.015). There was a significant correlation between the late H/M mIBG ratio and B-type natriuretic peptide (R = 0.77, p = 0.01) and systolic pulmonary pressure (R = 0.7, p = 0.05). No significant scintigraphic, functional or hemodynamic change was observed between the 2 evaluations in the 6 patients not treated with an LVAD.ConclusionsVentricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.