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. Methods and 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.

Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices

“…Baseline MSNA in their subjects was comparable to our cohort; however, their healthy control subjects had MSNA levels that were much higher than healthy control subjects that we have evaluated previously and were similar to MSNA levels in their LVAD patients. 4 Although they suggested that baroreceptor sensitivity remains intact with normal MSNA despite nonsignificant reductions in pulsatility, we were able to induce much larger changes in pulsatility by making upward and downward adjustments in pump speed and found that sympathetic tone is reduced through facilitation of the arterial baroreflex after the reintroduction of pulsatile flow.…”

“…5 Our group found previously that patients with CF-LVADs have marked increases in MSNA compared with healthy control subjects and patients with previous-generation pulsatile devices. 4 The current study extends these findings and ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ASA, aspirin; BMI, body mass index; bpm, beats per minute; CF, continuous-flow; DBP, diastolic blood pressure; ETCO 2 , end-tidal carbon dioxide; HR, heart rate; LVAD, left ventricular assist device; MAP, mean arterial pressure; MRA, mineralocorticoid receptor antagonist; MSNA, muscle sympathetic nerve activity; PI, pulsatility index; PP, pulse pressure; RPM, revolutions per minute; and SBP, systolic blood pressure.…”

“…[1][2][3] Although these devices have the advantage of small size and improved durability compared with previous-generation devices that were pulsatile, there are a number of risks associated with continuous-flow (CF) circulatory support, including dramatic increases in muscle sympathetic nerve activity (MSNA), 4 likely through a baroreceptor reflex pathway.…”

To Pulse or Not to Pulse, Is That the Question?

“…In their prior report, 5 MSNA in subjects with nonpulsatile LVADs was increased almost 2-fold compared with that of patients with pulsatile LVADs, yet average total peripheral resistance was similar in these 2 groups. No data were provided in that report or in the present publication concerning calf vascular resistance, cardiac output or its distribution to the kidney or other vascular beds, renal sodium retention, or exercise capacity.…”

“…In those with nonpulsatile compared with pulsatile LVADs, MSNA was 80% higher at rest and 70% higher during tilt, a difference these investigators attributed to diminished arterial mechanoreceptor stretch. 5 Cornwell et al 4 now report the findings of a protocol involving 13 patients with implanted Heartmate II continuous axial-flow devices designed to test the hypothesis that immediate changes in LVAD pump speed would elicit reflex muscle sympathetic firing responses by altering arterial pulse pressure and hence mechanoreceptor input to baroreceptor afferent nerves. 4 With participants supine, MSNA and a photoplethysmographic digital arterial waveform were recorded continuously while the prevailing LVAD pump speed was increased (to unload the left ventricle, reduce aortic valve opening, and diminish pulse pressure) or decreased (to achieve the converse) in 200-to 400-rpm steady-state increments and maintained at each velocity for up to 10 minutes.…”