Patients With Continuous-Flow Left Ventricular Assist Devices Provide Insight in Human Baroreflex Physiology

Abstract

Abstract-The superior clinical outcome of new continuous-flow left ventricular assist devices (LVADs) challenges the physiological dogma that cardiovascular autonomic homeostasis requires pulsatile blood flow and pressure. We tested the hypothesis that continuous-flow LVADs impair baroreflex control of sympathetic nerve traffic, thus further exacerbating sympathetic excitation. We included 9 male heart failure patients (26 -61 years; 18.9 -28.3 kg/m 2 ) implanted with a continuous-flow LVAD. We recorded ECG, respiration, finger blood pressure, brachial blood pressure, and muscle sympathetic nerve activity. After baseline measurements had been taken, patients underwent autonomic function testing including deep breathing, a Valsalva maneuver, and 15°head-up tilt. Finally, we increased the LVAD speed in 7 patients. Spontaneous sympathetic baroreflex sensitivity was analyzed. Brachial blood pressure was 99Ϯ4 mm Hg with 14Ϯ2 mm Hg finger pulse pressure. Muscle sympathetic nerve activity bursts showed a normal morphology, were linked to the cardiac cycle, and were suppressed during blood pressure increases. Mean burst frequency was lower compared with age-and body mass index-matched controls in 2 patients, slightly increased in 4 patients, and increased in 2 patients (Pϭ0.11). Muscle sympathetic nerve activity burst latency and the median values of the burst amplitude distribution were similar between groups. Muscle sympathetic nerve activity increased 4Ϯ1 bursts per minute with head-up tilt (PϽ0.0003) and decreased 3Ϯ4 bursts per minute (PϽ0.031) when LVAD speed was raised. The mean sympathetic baroreflex slope was Ϫ3.75Ϯ0.79%/mm Hg in patients and Ϫ3.80Ϯ0.55%/mm Hg in controls. We conclude that low pulse pressure levels are sufficient to restrain sympathetic nervous system activity through baroreflex mechanisms. 2 Access to cardiac transplantation, which improves symptoms and survival, is limited by donor organ shortage.2,3 Initially, left ventricular assist devices (LVADs) served as a short-term bridge to transplantation. Technology refinement and device miniaturization allowed LVAD-treated patients to leave the hospital for months or even years. End-stage heart failure patients equipped with pulsatile LVADs showed 48% reductions in total mortality compared with patients on optimal medical treatment. 4 Earlier pulsatile flow LVADs were bulky and associated with a high risk for infection, thromboembolism, and device failure.2,3 Recently developed LVADs produce continuous flow-through axial or centrifugal rotary pumps. Compared with pulsatile devices, patients with continuous-flow LVADs fared better in terms of cardiovascular morbidity, reoperations for device repair or replacement, and total mortality.2,5-8 Thus, continuous-flow LVAD use as a bridge to transplantation or as destination therapy is likely to increase. 2,4,7 The good clinical outcome challenges the physiological dogma that cardiovascular homeostasis, particularly baroreflex regulation, requires pulsatile blood flow and pressure. Pulsatile pressure mini...

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

“…Notably, Tank et al 19 performed a similar analysis of patients with centrifugal-flow (Heartware) ventricular assist devices and found that pulsatility was not significantly changed by increasing pump speed and that there was a very slight reduction in MSNA (by 3 bursts per minute) as pump speed was raised from baseline to 3200 RPM. 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.…”

“…Indeed, it may be that centrifugal-flow devices are less able to introduce pulsatile flow through modulations in pump speed. 19 Second, all of the patients were on β-blockers, which were held on the morning of the study. This eliminated the acute effects of β-blockade on MSNA, but we cannot rule out the possibility that chronic effects of the drug were still present.…”

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

“…Those living with LVADs constitute a small population but one for whom there has been an enormous investment in resources and personnel to ensure a good and enduring outcome with a high quality of life. The value of MSNA, as revealed by the present literature, [4][5][6] is that it could well be applied in future investigations to define the optimal degree of pulse and diastolic pressure for such individuals. …”

“…Increasing pump speed lowered pulse pressure to 5 mm Hg, yet MSNA fell. 6 A clinical stimulus to the present study was the investigators' contention that nonpulsatile flow induces a "hyperadrenergic environment." However, the average MSNA burst…”

“…1,[6][7][8] In contrast, in patients with chronic heart failure with reduced ejection fraction who have impaired exercise capacity, MSNA burst incidence commonly falls between 80 and 100 bursts per cardiac cycles. [7][8][9][10] Prior Heartmate II literature indicates that the circulatory stability achieved after ≥3 months is sufficient to improve cardiac sympathetic innervation and to establish a lower noradrenergic central set point.…”