title: Sympathetic neural and hemodynamic responses to upright tilt in patients with pulsatile and nonpulsatile left ventricular assist devices.
abstract: BACKGROUND
  Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First-generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are nonpulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans.
  
  
  RESULTS
  We evaluated patients with pulsatile (n=6) and nonpulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt while measuring hemodynamics and muscle sympathetic nerve activity. Patients with nonpulsatile devices had markedly elevated supine and upright muscle sympathetic nerve activity (mean±SD, 43±15 supine and 60±21 bursts/min at 60° head-up tilt) compared with patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, muscle sympathetic nerve activity was not different between patients with pulsatile flow and controls (P=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, whereas cardiac output was smaller, in LVAD patients compared with controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and nonpulsatile flow.
  
  
  CONCLUSIONS
  Heart failure patients with continuous, nonpulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Markham
authors.forename: Qi
authors.initials: Q
authors.lastname: Fu
authors.forename: M Dean
authors.initials: MD
authors.lastname: Palmer
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
authors.forename: Dan M
authors.initials: DM
authors.lastname: Meyer
authors.forename: Brian T
authors.initials: BT
authors.lastname: Bethea
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Hastings
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibata
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Levine
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D062186:Arterial Pressure; D017704:Baroreflex; D015415:Biomarkers / Q000097:blood; D002302:Cardiac Output; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D006353:Heart-Assist Devices; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation*; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D011474:Prosthesis Design; D011673:Pulsatile Flow; D016683:Supine Position; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D013781:Texas; D018667:Tilt-Table Test; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine