Myocardial sympathetic innervation and long-term left ventricular mechanical unloading

Stavros G Drakos, Theodoros Athanasoulis, Konstantinos G Malliaras, John V Terrovitis, Nikolaos Diakos, Dimitrios Koudoumas, Argirios S Ntalianis, Stergios P Theodoropoulos, Magdi H Yacoub, John N Nanas
JACC. Cardiovascular Imaging 2010, 3 (1): 64-70

OBJECTIVES: The purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart.

BACKGROUND: Ventricular 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.

METHODS: We 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.

RESULTS: After 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.

CONCLUSIONS: Ventricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.

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