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Myocardial Sympathetic Innervation and Long-Term Left Ventricular Mechanical Unloading

Stavros G. Drakos, MD^_*, Theodoros Athanasoulis, MD, Konstantinos G. Malliaras, MD^_*, John V. Terrovitis, MD^_*, Nikolaos Diakos, MD^_*, Dimitrios Koudoumas, MD^_*, Argirios S. Ntalianis, MD^_*, Stergios P. Theodoropoulos, MD, Magdi H. Yacoub, MD^,, John N. Nanas, MD, PhD^_*,_*

^_* 3rd Cardiology Department and Department of Clinical Therapeutics, University of Athens, Athens, Greece
Division of Nuclear Medicine, Alexandra Hospital, Athens, Greece
Division of Cardiothoracic Surgery, IASO General Hospital, Athens, Greece
Harefield Heart Science Center and the Magdi Yacoub Institute, Harefield, United Kingdom

^_* Reprint requests and correspondence: Dr. John N. Nanas, 3rd Cardiology Department, University of Athens School of Medicine, 24 Makedonias, 10433 Athens, Greece (Email: jnanas{at}ath.forthnet.gr).

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.

Key Words: heart failure • ¹²³I-metaiodobenzylguanidine • myocardial scintigraphy • myocardial sympathetic innervation • reverse cardiac remodeling

Abbreviations and Acronyms   HF = heart failure   H/M = heart-to-mediastinum   LV = left ventricular   LVAD = left ventricular assist device   mIBG = meta-iodobenzylguanidine

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