The importance of pulsatility in modern mechanical circulatory support devices

In end-stage heart failure patients, there are limited treatment options available. While heart transplantation is the current gold standard, it is a numerically inadequate solution. Modern durable mechanical circulatory support (MCS) devices, such as ventricular assist devices (VADs) can provide bridging therapy to transplantation, or alternatively function as a destination therapy. These devices lack pulsatility which has important physiological implications. The goal of this thesis is to highlight the importance of pulsatility in modern MCS devices by defining pulsatility, quantifying it, assessing the impact of non-pulsatile flow as well as looking at future (pulsatile) devices. Several related studies were conducted to achieve the thesis goal. These studies included three literature reviews (defining pulsatility, exploring vasoplegia post device explant and evaluating the clinical utility of log files in mitigating problems associated with non-pulsatile flow). A retrospective study was conducted to analyse the distribution of vasoplegia amongst patients undergoing VAD explant and heart transplant in a single Australian centre. Additionally, one prospective study was conducted to explore the clinical utility of using pulsatility index (PI) to quantify pulsatility and two prospective studies assessed the anatomical and surgical compatibility of the BiVACOR total artificial heart (TAH) – a device capable of generating pulsatile flow. MCS devices provide an important tool to manage patients with end-stage heart failure. These devices operate on a continuous flow basis that is likely to have unique physiological implications such as pump thrombosis, increased stroke rate and gastrointestinal bleeding. There is limited consensus in defining or quantifying pulsatility within this patient cohort, however pulsatility index may be a useful measure to aid patient management. The BiVACOR TAH was found to be an anatomically compatible pump, with a familiar implant technique that may overcome problems associated with continuous flow through generating pulsatile flow by speed variation

人工心臓への適用を目的としたダブルステータ型磁気浮上ポンプの開発

The clinical pharmacology of fentanyl and alfentanil was examined in opioid-experienced volunteers with agonist and antagonist sensitivity measures. Two studies used within-subject, placebo-controlled, crossover designs. In study 1, fentanyl (0.125, 0.25 mg/70 kg i.v.) was followed at 0, 20, 60 and 180 min by naloxone (10 mg/70 kg i.m.). Agonist effects during 180-min and 0-min (control; simultaneous fentanyl-naloxone i.v. infusion) challenge sessions were compared. Fentanyl rapidly constricted pupils, depressed respiration and produced subjective high and opiate symptoms lasting 60 to 120 min, depending on the measure. Naloxone precipitated withdrawal symptoms of comparable intensity at each challenge point. In study 2, fentanyl (0.125, 0.25 mg/70 kg i.v.), alfentanil (1, 2 mg/70 kg i.v.) and saline were followed at 1 and 6 hr by naloxone (10 mg/70 kg i.m.). Agonist effects were examined during 6-hr challenge sessions. The two drugs produced a comparable range of effects with similar peak magnitude for 0.125 mg/70 kg fentanyl and 1 mg/70 kg alfentanil and for 0.25 mg/70 kg fentanyl and 2 mg/70 kg alfentanil. Alfentanil\u27s duration of action was brief ( \u3c 60 min). Withdrawal was precipitated at 6 hr only after 0.25 mg/70 kg fentanyl. These findings support typical mu opioid characteristics (pleasurable subjective effects, physical dependence) for both drugs, differential duration of action (fentanyl \u3e alfentanil) and peak effects consistent with a 1:8 (fentanyl/alfentanil) potency ratio

New Continuous-Flow Total Artificial Heart For Use in Smaller Sized Adults & Pediatric Patients

Congestive heart failure (CHF) is a progressive and debilitating disease that affects millions of people worldwide. Hundreds of thousands of new cases of CHF are diagnosed each year in the U.S., and this high volume of patients costs the healthcare industry tens of billions annually. The limited number of donor hearts and limited long-term effectiveness of pharmacologic treatment necessitate the use of mechanical circulatory support (MCS) alternatives. Clinical trials of MCS devices have demonstrated that patients derive substantial survival and quality of life benefits from long-term MCS. Only two total artificial hearts (TAHs) are approved for clinical implantation in the U.S., and the implementation of TAHs in the treatment of patients with CHF has increased more than 3 fold in 6 years. These devices and other new TAHs that are under development, however, have several design limitations and challenges, such as thromboembolic events, neurologic impairment, risk of infection due to large size, and infection at the abdominal site of the percutaneous driveline. Additional design limitations include lack of ambulation due to a sizeable drive console or a heavy portable unit, non-pulsatile blood flow conditions, and the use of polyurethane membranes and valves which risks rupture or failure after repetitive flexions or openings. To address these limitations and to provide a new therapeutic solution, we seek to develop an innovative therapeutic alternative: a unique hybrid-design, continuous flow, implantable, magnetically levitated TAH (Dragon Heart). The Dragon Heart is designed to support pediatric and adult patients (BSA > 0.95 sq. meters) with CHF. This TAH has only 2 moving parts - an axial impeller for the pulmonary circulation and a centrifugal impeller for the systemic circulation. This device utilizes the latest generation of magnetic bearing technology to levitate the impellers, thus enabling a longer operational lifespan of 15-20 years and larger clearances between the rotating impellers and pump housing. Larger clearances lead to lower fluid shear stresses, hence mitigating the risk of thrombosis and hemolysis. This design avoids the use of mechanical or biologic valves and will have an antithrombogenic coating applied to blood-contacting surfaces, thus further reducing the risk of thrombosis. It will incorporate state-of-theart monitoring with Wifi-based sensors to report operational status and will be able to produce both continuous and pulsatile blood flow. A transcutaneous energy transfer system using wireless technology will be incorporated to eliminate the percutaneous driveline. The compact Dragon TAH, which has a target diameter and height of 60 mm by 50 mm, will produce the physiologic pressures and flows necessary to support CHF patients. This thesis project involved the initial steps in the design and development of the Dragon Heart. The pump geometries (axial and centrifugal) were established using standard pump design equations and available literature on similar pumps. Computational modeling using ANSYS CFX 15.0 was performed to gain insight into the performance of the pump geometries. The axial and centrifugal pump designs were optimized twice to reduce the outer diameter without compromising pump performance. These computational models served as the foundation by which prototype manufacturing was completed for hydraulic testing. Two hydraulic test rigs were constructed to evaluate the performance of the axial and centrifugal pump prototypes. A blood analog solution of water and glycerin was utilized for the experiments. The computational studies and prototype testing revealed that the Dragon Heart is capable of delivering the target blood flows of 1-6.5 L/min and pressure rises of 15-25 mmHg for the pulmonary circulation and 80-140 mmHg for the systemic circulation at rotational speeds of 2,000-12,000 RPM with power consumptions of 3-6 watts. This work successfully reflects the first design phase of the Dragon Heart and represents the foundation by which to begin Phase II optimization and development. The long-term goal of this research is to commercialize a novel, less expensive, more compact, low thrombus, and effective therapeutic alternative for adult and pediatric patients with CHF, thereby saving thousands of lives annually.M.S., Biomedical Engineering -- Drexel University, 201

Axial Magnetic Bearing Development for the BiVACOR Rotary BiVAD/TAH

A suspension system for the BiVACOR biventricular assist device (BiVAD) has been developed and tested. The device features two semi-open centrifugal impellers mounted on a common rotating hub. Flow balancing is achieved through the movement of the rotor in the axial direction. The rotor is suspended in the pump casings by an active magnetic suspension system in the axial direction and a passive hydrodynamic bearing in the radial direction. This paper investigates the axial movement capacity of themagnetic bearing system and the power consumption at various operating points. The force capacity of the passive hydrodynamic bearing is investigated using a viscous glycerol solution. Axial rotor movement in the range of ±0.15 mm is confirmed and power consumption is under 15.5 W. The journal bearing is shown to stabilize the rotor in the radial direction at the required operating speed. Magnetic levitation is a viable suspension technique for the impeller of an artificial heart to improve device lifetime and reduce blood damage

Soporte mecánico circulatorio contemporáneo. De corta a larga duración; una opción real.

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatría. Fecha de Lectura: 25-06-202

Inflow cannula design for biventricular assist devices

Cardiovascular diseases are a leading cause of death throughout the developed world. With the demand for donor hearts far exceeding the supply, a bridge-to-transplant or permanent solution is required. This is currently achieved with ventricular assist devices (VADs), which can be used to assist the left ventricle (LVAD), right ventricle (RVAD), or both ventricles simultaneously (BiVAD). Earlier generation VADs were large, volume-displacement devices designed for temporary support until a donor heart was found. The latest generation of VADs use rotary blood pump technology which improves device lifetime and the quality of life for end stage heart failure patients. VADs are connected to the heart and greater vessels of the patient through specially designed tubes called cannulae. The inflow cannulae, which supply blood to the VAD, are usually attached to the left atrium or ventricle for LVAD support, and the right atrium or ventricle for RVAD support. Few studies have characterized the haemodynamic difference between the two cannulation sites, particularly with respect to rotary RVAD support. Inflow cannulae are usually made of metal or a semi-rigid polymer to prevent collapse with negative pressures. However suction, and subsequent collapse, of the cannulated heart chamber can be a frequent occurrence, particularly with the relatively preload insensitive rotary blood pumps. Suction events may be associated with endocardial damage, pump flow stoppages and ventricular arrhythmias. While several VAD control strategies are under development, these usually rely on potentially inaccurate sensors or somewhat unreliable inferred data to estimate preload. Fixation of the inflow cannula is usually achieved through suturing the cannula, often via a felt sewing ring, to the cannulated chamber. This technique extends the time on cardiopulmonary bypass which is associated with several postoperative complications. The overall objective of this thesis was to improve the placement and design of rotary LVAD and RVAD inflow cannulae to achieve enhanced haemodynamic performance, reduced incidence of suction events, reduced levels of postoperative bleeding and a faster implantation procedure. Specific objectives were: * in-vitro evaluation of LVAD and RVAD inflow cannula placement, * design and in-vitro evaluation of a passive mechanism to reduce the potential for heart chamber suction, * design and in-vitro evaluation of a novel suture-less cannula fixation device. In order to complete in-vitro evaluation of VAD inflow cannulae, a mock circulation loop (MCL) was developed to accurately replicate the haemodynamics in the human systemic and pulmonary circulations. Validation of the MCL’s haemodynamic performance, including the form and magnitude of pressure, flow and volume traces was completed through comparisons of patient data and the literature. The MCL was capable of reproducing almost any healthy or pathological condition, and provided a useful tool to evaluate VAD cannulation and other cardiovascular devices. The MCL was used to evaluate inflow cannula placement for rotary VAD support. Left and right atrial and ventricular cannulation sites were evaluated under conditions of mild and severe heart failure. With a view to long term LVAD support in the severe left heart failure condition, left ventricular inflow cannulation was preferred due to improved LVAD efficiency and reduced potential for thrombus formation. In the mild left heart failure condition, left atrial cannulation was preferred to provide an improved platform for myocardial recovery. Similar trends were observed with RVAD support, however to a lesser degree due to a smaller difference in right atrial and ventricular pressures. A compliant inflow cannula to prevent suction events was then developed and evaluated in the MCL. As rotary LVAD or RVAD preload was reduced, suction events occurred in all instances with a rigid inflow cannula. Addition of the compliant segment eliminated suction events in all instances. This was due to passive restriction of the compliant segment as preload dropped, thus increasing the VAD circuit resistance and decreasing the VAD flow rate. Therefore, the compliant inflow cannula acted as a passive flow control / anti-suction system in LVAD and RVAD support. A novel suture-less inflow cannula fixation device was then developed to reduce implantation time and postoperative bleeding. The fixation device was evaluated for LVAD and RVAD support in cadaveric animal and human hearts attached to a MCL. LVAD inflow cannulation was achieved in under two minutes with the suture-less fixation device. No leakage through the suture-less fixation device – myocardial interface was noted. Continued development and in-vivo evaluation of this device may result in an improved inflow cannulation technique with the potential for off-bypass insertion. Continued development of this research, in particular the compliant inflow cannula and suture-less inflow cannulation device, will result in improved postoperative outcomes, life span and quality of life for end-stage heart failure patients