Estimation of Left Ventricular Stroke Work for Rotary Left Ventricular Assist Devices.

Continuous monitoring of left ventricular stroke work (LVSW) may improve the medical management of patients with rotary left ventricular assist devices (LVAD). However, implantable pressure-volume sensors are limited by measurement drift and hemocompatibility. Instead, estimator algorithms derived from rotary LVAD signals may be a suitable alternative. An LVSW estimator algorithm was developed and evaluated in a range of in vitro and ex vivo cardiovascular conditions during full assist (closed aortic valve [AoV]) and partial assist (opening AoV) mode. For full assist, the LVSW estimator algorithm was based on LVAD flow, speed, and pump pressure head, whereas for partial assist, the LVSW estimator combined the full assist algorithm with an estimate of AoV flow. During full assist, the LVSW estimator demonstrated a good fit in vitro and ex vivo (R 2 : 0.97 and 0.86, respectively) with errors of ± 0.07 J. However, LVSW estimator performance was reduced during partial assist, with in vitro : R 2 : 0.88 and an error of ± 0.16 J and ex vivo : R 2 : 0.48 with errors of ± 0.11 J. Further investigations are required to improve the LVSW estimate with partial assist; however, this study demonstrated promising results for a continuous estimate of LVSW for rotary LVADs.

A Sensorless Modular Multiobjective Control Algorithm for Left Ventricular Assist Devices: A Clinical Pilot Study.

Background: Contemporary Left Ventricular Assist Devices (LVADs) mainly operate at a constant speed, only insufficiently adapting to changes in patient demand. Automatic physiological speed control promises tighter integration of the LVAD into patient physiology, increasing the level of support during activity and decreasing support when it is excessive. Methods: A sensorless modular control algorithm was developed for a centrifugal LVAD (HVAD, Medtronic plc, MN, USA). It consists of a heart rate-, a pulsatility-, a suction reaction-and a supervisor module. These modules were embedded into a safe testing environment and investigated in a single-center, blinded, crossover, clinical pilot trial (clinicaltrials.gov, NCT04786236). Patients completed a protocol consisting of orthostatic changes, Valsalva maneuver and submaximal bicycle ergometry in constant speed and physiological control mode in randomized sequence. Endpoints for the study were reduction of suction burden, adequate pump speed and flowrate adaptations of the control algorithm for each protocol item and no necessity for intervention via the hardware safety systems. Results: A total of six patients (median age 53.5, 100% male) completed 13 tests in the intermediate care unit or in an outpatient setting, without necessity for intervention during control mode operation. Physiological control reduced speed and flowrate during patient rest, in sitting by a median of -75 [Interquartile Range (IQR): -137, 65] rpm and in supine position by -130 [-150, 30] rpm, thereby reducing suction burden in scenarios prone to overpumping in most tests [0 [-10, 2] Suction events/minute] in orthostatic upwards transitions and by -2 [-6, 0] Suction events/min in Valsalva maneuver. During submaximal ergometry speed was increased by 86 [31, 193] rpm compared to constant speed for a median flow increase of 0.2 [0.1, 0.8] L/min. In 3 tests speed could not be increased above constant set speed due to recurring suction and in 3 tests speed could be increased by up to 500 rpm with a pump flowrate increase of up to 0.9 L/min. Conclusion: In this pilot study, safety, short-term efficacy, and physiological responsiveness of a sensorless automated speed control system for a centrifugal LVAD was established. Long term studies are needed to show improved clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04786236.

The left ventricular assist device as a patient monitoring system.

Technological progress of left ventricular assist devices (LVADs) towards rotary blood pumps and the optimization of medical management contributed to the significant improvements in patient survival as well as LVAD support duration. Even though LVAD therapy is now well-established for end-stage heart failure patients, the long-term occurrence of adverse events (AE) such as bleeding, infection or stroke, still represent a relevant burden. An early detection of AE, before onset of major symptoms, can lead to further optimization of patient treatment and thus mitigate the burden of AE. Continuous patient monitoring facilitates identification of pathophysiological states and allows anticipation of AE to improve patient management. In this paper, methods, algorithms and possibilities for continuous patient monitoring based on LVAD data are reviewed. While experience with continuous LVAD monitoring is currently limited to a few centers worldwide, the pace of developments in this field is fast and we expect these technologies to have a global impact on the well-being of LVAD patients.

Hemodynamic exercise responses with a continuous-flow left ventricular assist device: Comparison of patients' response and cardiorespiratory simulations.

BACKGROUND: Left ventricular assist devices (LVADs) are an established treatment for end stage heart failure patients. As LVADs do not currently respond to exercise demands, attention is also directed towards improvements in exercise capacity and resulting quality of life. The aim of this study was to explore hemodynamic responses observed during maximal exercise tests to infer underlying patient status and therefore investigate possible diagnostics from LVAD derived data and advance the development of physiologically adaptive LVAD controllers. METHODS: High resolution continuous LVAD flow waveforms were recorded from 14 LVAD patients and evaluated at rest and during maximum bicycle exercise tests (n = 24). Responses to exercise were analyzed in terms of an increase (↑) or decrease (↓) in minimum (QMIN), mean (QMEAN), maximum flow (QMAX) and flow pulsatility (QP2P). To interpret clinical data, a cardiorespiratory numerical simulator was used that reproduced patients' hemodynamics at rest and exercise. Different cardiovascular scenarios including chronotropic and inotropic responses, peripheral vasodilation, and aortic valve pathologies were simulated systematically and compared to the patients' responses. RESULTS: Different patients' responses to exercise were observed. The most common response was a positive change of ΔQMIN↑ and ΔQP2P↑ from rest to exercise (70% of exercise tests). Two responses, which were never reported in patients so far, were distinguished by QMIN↑ and QP2P↓ (observed in 17%) and by QMIN↓ and QP2P↑ (observed in 13%). The simulations indicated that the QP2P↓ can result from a reduced left ventricular contractility and that the QMIN↓ can occur with a better left ventricular contractility and/or aortic insufficiency. CONCLUSION: LVAD flow waveforms determine a patients' hemodynamic "fingerprint" from rest to exercise. Different waveform responses to exercise, including previously unobserved ones, were reported. The simulations indicated the left ventricular contractility as a major determinant for the different responses, thus improving patient stratification to identify how patient groups would benefit from exercise-responsive LVAD control.

Continuous LVAD monitoring reveals high suction rates in clinically stable outpatients.

Suction of the left ventricle can lead to potentially life-threatening events in left ventricular assist device (LVAD) patients. With the resolution of currently available clinical LVAD monitoring healthcare professionals are unable to evaluate patients' suction occurrences in detail. This study investigates occurrences and durations of suction events and their associations with tachycardia in stable outpatients. Continuous high-resolution LVAD data from HVAD patients were analyzed in the early outpatient period for 15 days. A validated suction detection from LVAD signals was used. Suction events were evaluated as suction rates, bursts of consecutive suction beats, and clusters of suction beats. The occurrence of tachycardia was analyzed before, during, and after suction clusters. Furthermore, blood work, implant strategy, LVAD speed setting, inflow cannula position, left ventricular diameters, and adverse events were evaluated in these patients. LVAD data of 10 patients was analyzed starting at 78 ± 22 postoperative days. Individuals' highest suction rates per hour resulted in a median of 11% (range 3%-61%). Bursts categorized as consecutive suction beats with n = 2, n = 3-5, n = 6-15, and n > 15 beats were homogenously distributed with 10.3 ± 0.8% among all suction beats. Larger suction bursts were followed by shorter suction-free periods. Tachycardia during suction occurred in 12% of all suction clusters. Significant differences in clinical parameters between individuals with high and low suction rates were only observed in left ventricular end-diastolic and end-systolic diameters (P < .02). Continuous high-resolution LVAD monitoring sheds light on outpatient suction occurrences. Interindividual and intraindividual characteristics of longitudinal suction rates were observed. Longer suction clusters have higher probabilities of tachycardia within the cluster and more severe types of suction waveforms. This work shows the necessity of improved LVAD monitoring and the implementation of an LVAD speed control to reduce suction rates and their concomitant burden on the cardiovascular system.

LVAD speed increase during exercise, which patients would benefit the most? A simulation study.

Patients supported with a left ventricular assist device (LVAD) have impaired cardiovascular adaptations during exercise, resulting in reduced total cardiac output and exercise intolerance. The aim of this study is to report associations among these impaired cardiovascular parameters and exercise hemodynamics, and to identify in which conditions an LVAD speed increase can provide substantial benefits to exercise. A cardiorespiratory simulator was used to reproduce the average hemodynamics of LVAD patients at exercise. Then, a sensitivity study was conducted where cardiovascular parameters were changed individually ±20% of their baseline value at exercise (heart rate, left/right ventricular contractility, total peripheral resistance, and valve pathologies). Simulations were performed at a baseline LVAD speed of 2700 rpm and repeated at 3500 rpm to evaluate the benefits of a higher LVAD support on hemodynamics. Total cardiac output (TCO) was mostly impaired by a poor left ventricular contractility or vasodilation at exercise (-0.6 L/min), followed by a poor chronotropic response (-0.3 L/min) and by a poor right ventricular contractility (-0.2 L/min). LVAD speed increase better unloads the left ventricle and improves total cardiac output in all the simulated conditions. The most substantial benefits from LVAD speed increase were observed in case of poor left ventricular contractility (TCO + 1.6 L/min) and vascular dysfunction (TCO + 1.4 L/min) followed by lower heart rate (TCO + 1.3 L/min) and impaired right ventricular contractility (TCO + 1.1 L/min). Despite the presence of the LVAD, exercise hemodynamic is strongly depending on the ability of the cardiovascular system to adapt to exercise. A poor left ventricular inotropic response and a poor vascular function can strongly impair cardiac output at exercise. In these conditions, LVAD speed increase can be an effective strategy to augment total cardiac output and unload the left ventricle. These results evidence the need to design a physiological LVAD speed controller, tailored on specific patient's needs.

Early Detection of Pump Thrombosis in Patients With Left Ventricular Assist Device.

Pump thrombosis (PT) is a serious adverse event in patients receiving left ventricular assist devices (LVAD). The study aims to determine whether pump parameters and clinical data may enable early detection of PT. This retrospective study included 88 patients who received an LVAD between 2012 and 2015 among which those with intra-PT were identified. In a propensity score-matched control group observation, time periods were matched with time before thrombosis. International normalized ratio (INR) time in therapeutic range (TTR) and lactate dehydrogenase (LDH) were analyzed for 60 days preceding PT. Furthermore, pump data (power, flow, and speed) in HeartWare ventricular assist devices (HVAD) patients were analyzed 7 days before PT using a mixed-design analysis of variance to investigate temporal changes in pump data. Pump thrombosis occurred in 15 patients (13 males, age 58 ± 10 years, 7 HeartMate II and 8 HVAD). International normalized ratio therapeutic range (2.0-3.0) and acetylsalicylic acid daily doses (100-200 mg) were similar for both groups, but patients with PT had lower TTR (36% vs. 65%; p = 0.025). No significant difference in LVAD power between groups was seen at baseline (p = 0.31), and power did not change in the control group over time (p > 0.99). Lactate dehydrogenase increased already 1 week prior PT and power from 4.4 ± 0.8 W at baseline to 4.9 ± 0.8 W (p = 0.007) 2 days before readmission and to 6.5 ± 1.8 W (p = 0.015) at readmission. Pump thrombosis is associated with a lower percentage of INR TTR and elevated LDH before the event. A better monitoring of pump parameters would enable PT detection already up to 2 days in advance.

Effects of Functional Electrical Stimulation on Denervated Laryngeal Muscle in a Large Animal Model.

Bilateral vocal fold paralysis (BVCP) is a life-threatening condition that follows injury to the Recurrent Laryngeal nerve (RLn) and denervation of the intrinsic laryngeal musculature. Functional electrical stimulation (FES) enables restoration and control of a wide variety of motor functions impaired by lower motor neuron lesions. Here we evaluate the effects of FES on the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle in a large animal model of RLn injury. Ten horses were instrumented with two quadripolar intramuscular electrodes in the left PCA muscle. Following a 12-week denervation period, the PCA was stimulated using a once-daily training session for 8 weeks in seven animals. Three animals were used as unstimulated controls. Denervation produced a significant increase in rheobase (P < 0.001). Electrical stimulation produced a 30% increase in fiber diameter in comparison with the unstimulated control group (33.9 ± 2.6 µm FES+, 23.6 ± 4.2 µm FES-, P = 0.04). A trend toward a decrease in the proportion of type 1 (slow) fibers and an increase in type 2a (fast) fibers was also observed. Despite these changes, improvement in PCA function at rest was not observed. These data suggest that electrical stimulation using a relatively conservative set of stimulation parameters can reverse the muscle fiber atrophy produced by complete denervation while avoiding a shift to a slow (type 1) fiber type.