Research and development of ventricular assist devices from a single center in Latin America

OBJECTIVES: Ventricular assist devices have been widely accepted as an alternative treatment for advanced heart failure, while heart transplantation is a limited procedure because of the shortage of donors. In face of a scarce availability of these devices, many centers around the world have developed their own technologies. The Institute Dante Pazzanese of Cardiology holds a dedicated engineering center for mechanical circulatory support, being responsible for creating several prototypes and notable devices, like the first Brazilian artificial heart. The objectives of this study were to provide both a historical overview and a detailed characterization of each original device developed by the center. METHODS: We describe historical and technical features of the main ventricular assist devices developed at the Institute Dante Pazzanese of Cardiology through a focused review on the institute's scientific and technical production on ventricular assist devices or blood pumps, from 1990 to 2022, indexed in the electronic databases Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, and the Scientific Electronic Library Online (SciELO). RESULTS: The following devices were selected from the review: (1) The Spiral Pump is a disposable centrifugal pump with an internal conically shaped rotor, a spiral impeller, which carries threads on its surface. The device was designed for cardiopulmonary bypass in 1992, passed through consecutive design modifications and preclinical tests until approval for clinical application in 2007. (2) The Auxiliary Total Artificial Heart is an electromechanical pulsatile blood pump with left and right chambers, originally designed in 1995 to work as a heterotopic artificial heart. Preclinical studies evaluated hydrodynamic performance in mock circulatory loops and in vivo implants were performed in calves from 1999 to 2009. In 2012, it became the first nationally conceived artificial heart approved for clinical trials in Brazil. (3) The Implantable Centrifugal Blood Pump was conceived in 2006 for long-term circulatory assistance with a unique impeller design concept producing a mixed flow. Preclinical studies included hydrodynamic and hemolysis tests, analysis in a hybrid cardiovascular simulator and anatomical positioning in calves. (4) The Apico-Aortic Blood Pump consists of a miniaturized centrifugal pump originally conceived in 2012 for bridge to transplantation strategy. Preclinical studies included hydrodynamic and hemolysis tests, analysis in a hybrid cardiovascular simulator and anatomical positioning in pigs. (5) The Temporary Circulatory Support Device is a new centrifugal blood pump for temporary ventricular assistance developed with the purpose of bridge to decision or bridge to recovery strategies. Originally conceived in 2013, preclinical studies on the device consisted only of hydrodynamic and hemolysis tests. CONCLUSION: From the academic point of view, Brazil count on a few groups with a considerable output in ventricular assist device research and development. Notable devices produced at Institute Dante Pazzanese of Cardiology, from a total artificial heart to varied and innovative centrifugal pumps, have demonstrated excellent results for future clinical applications. More financial and institutional support are needed for the continuation of these promising research projects.

In vitro evaluation of multi­objective physiological control of the centrifugal blood pump

Left ventricular assist devices (LVADs) have been used as a bridge to transplantation or as destination therapy to treat patients with heart failure (HF). The inability of control strategy to respond automatically to changes in hemodynamic conditions can impact the patients' quality of life. The developed control system/algorithm consists of a control system that harmoniously adjusts pump speed without additional sensors, considering the patient's clinical condition and his physical activity. The control system consists of three layers: (a) Actuator speed control; (b) LVAD flow control (FwC); and (c) Fuzzy control system (FzC), with the input variables: heart rate (HR), mean arterial pressure (MAP), minimum pump flow, level of physical activity (data from patient), and clinical condition (data from physician, INTERMACS profile). FzC output is the set point for the second LVAD control schemer (FwC) which in turn adjusts the speed. Pump flow, MAP, and HR are estimated from actuator drive parameters (speed and power). Evaluation of control was performed using a centrifugal blood pump in a hybrid cardiovascular simulator, where the left heart function is the mechanical model and right heart function is the computational model. The control system was able to maintain MAP and cardiac output in the physiological level, even under variation of EF. Apart from this, also the rotational pump speed is adjusted following the simulated clinical condition. No backflow from the aorta in the ventricle occurred through LVAD during tests. The control algorithm results were considered satisfactory for simulations, but it still should be confirmed during in vivo tests.

Apical aortic blood pump preclinical assessment for long­term use: durability test and stator topology to reduce wear in the bearing system

This study presents an assessment for long­term use of the apical aortic blood pump (AABP), focusing on wear reduction in the bearing system. AABP is a centrifugal left ventricle assist device initially developed for bridge to transplant application. To analyze AABP performance in long­term applications, a durability test was performed. This test indicated that wear in the lower bearing pivot causes device failure in long­term. A wear test in the bearing system was conducted to demonstrate the correlation of the load in the bearing system with wear. Results from the wear test showed a direct correlation between load and wear at the lower bearing pivot. In order to reduce load, thus reducing wear, a new stator topology has been proposed. In this topology, a radial stator would replace the axial stator previously used. Another durability test with the new stator has accounted twice the time without failure when compared with the original model.

In vitro evaluation of multi-objective physiological control of the centrifugal blood pump.

Left ventricular assist devices (LVADs) have been used as a bridge to transplantation or as destination therapy to treat patients with heart failure (HF). The inability of control strategy to respond automatically to changes in hemodynamic conditions can impact the patients' quality of life. The developed control system/algorithm consists of a control system that harmoniously adjusts pump speed without additional sensors, considering the patient's clinical condition and his physical activity. The control system consists of three layers: (a) Actuator speed control; (b) LVAD flow control (FwC); and (c) Fuzzy control system (FzC), with the input variables: heart rate (HR), mean arterial pressure (MAP), minimum pump flow, level of physical activity (data from patient), and clinical condition (data from physician, INTERMACS profile). FzC output is the set point for the second LVAD control schemer (FwC) which in turn adjusts the speed. Pump flow, MAP, and HR are estimated from actuator drive parameters (speed and power). Evaluation of control was performed using a centrifugal blood pump in a hybrid cardiovascular simulator, where the left heart function is the mechanical model and right heart function is the computational model. The control system was able to maintain MAP and cardiac output in the physiological level, even under variation of EF. Apart from this, also the rotational pump speed is adjusted following the simulated clinical condition. No backflow from the aorta in the ventricle occurred through LVAD during tests. The control algorithm results were considered satisfactory for simulations, but it still should be confirmed during in vivo tests.

Apical aortic blood pump preclinical assessment for long-term use: Durability test and stator topology to reduce wear in the bearing system.

This study presents an assessment for long-term use of the apical aortic blood pump (AABP), focusing on wear reduction in the bearing system. AABP is a centrifugal left ventricle assist device initially developed for bridge to transplant application. To analyze AABP performance in long-term applications, a durability test was performed. This test indicated that wear in the lower bearing pivot causes device failure in long-term. A wear test in the bearing system was conducted to demonstrate the correlation of the load in the bearing system with wear. Results from the wear test showed a direct correlation between load and wear at the lower bearing pivot. In order to reduce load, thus reducing wear, a new stator topology has been proposed. In this topology, a radial stator would replace the axial stator previously used. Another durability test with the new stator has accounted twice the time without failure when compared with the original model.

Centrifugal blood pump for temporary ventricular assist devices with low priming and ceramic bearings.

A new model of centrifugal blood pump for temporary ventricular assist devices has been developed and evaluated. The design of the device is based on centrifugal pumping principles and the usage of ceramic bearings, resulting in a pump with reduced priming (35 ± 2 mL) that can be applied for up to 30 days. Computational fluid dynamic (CFD) analysis is an efficient tool to optimize flow path geometry, maximize hydraulic performance, and minimize shear stress, consequently decreasing hemolysis. Initial studies were conducted by analyzing flow behavior with different impellers, aiming to determine the best impeller design. After CFD studies, rapid prototyping technology was used for production of pump prototypes with three different impellers. In vitro experiments were performed with those prototypes, using a mock loop system composed of Tygon tubes, oxygenator, digital flow meter, pressure monitor, electronic driver, and adjustable clamp for flow control, filled with a solution (1/3 water, 1/3 glycerin, 1/3 alcohol) simulating blood viscosity and density. Flow-versus-pressure curves were obtained for rotational speeds of 1000, 1500, 2000, 2500, and 3000 rpm. As the next step, the CFD analysis and hydrodynamic performance results will be compared with the results of flow visualization studies and hemolysis tests.

Study of a centrifugal blood pump in a mock loop system.

An implantable centrifugal blood pump (ICBP) is being developed to be used as a ventricular assist device (VAD) in patients with severe cardiovascular diseases. The ICBP system is composed of a centrifugal pump, a motor, a controller, and a power supply. The electricity source provides power to the controller and to a motor that moves the pump's rotor through magnetic coupling. The centrifugal pump is composed of four parts: external conical house, external base, impeller, and impeller base. The rotor is supported by a pivot bearing system, and its impeller base is responsible for sheltering four permanent magnets. A hybrid cardiovascular simulator (HCS) was used to evaluate the ICBP's performance. A heart failure (HF) (when the heart increases beat frequency to compensate for decrease in blood flow) was simulated in the HCS. The main objective of this work is to analyze changes in physiological parameters such as cardiac output, blood pressure, and heart rate in three situations: healthy heart, HF, and HF with left circulatory assistance by ICBP. The results showed that parameters such as aortic pressure and cardiac output affected by the HF situation returned to normal values when the ICBP was connected to the HCS. In conclusion, the test results showed satisfactory performance for the ICBP as a VAD.

In vitro assessment of the Apico Aortic Blood Pump: anatomical positioning, hydrodynamic performance, hemolysis studies, and analysis in a hybrid cardiovascular simulator.

The Apico Aortic Blood Pump (AABP) is a centrifugal continuous flow left ventricular assist device (LVAD) with ceramic bearings. The device is in the initial development phase and is being designed to be attached directly to the left ventricular apex by introducing an inlet cannula. This paper reports results from in vitro experiments. In order to evaluate implantation procedures and device dimensioning, in vitro experiments included an anatomic positioning study for the analysis of surgical implantation procedure and device dimensions and positioning that was performed using the body of a pig. The results revealed no damage caused by the device, and the surgical implantation procedure was considered feasible. Hydrodynamic performance curves were obtained to verify the applicability of the device as an LVAD, showing adequate performance. Mechanical blood trauma was analyzed through 6-h hemolysis tests, with total pressure head of 100 mm Hg and flow of 5 L/min. Mean normalized index of hemolysis was 0.009 g/100 L (±0.002 g/100 L). Studies using a hybrid cardiovascular simulator were conducted for three types of circulatory conditions: normal healthy conditions, concentric hypertrophic heart failure (CHHF), and CHHF with AABP assistance. Analysis of cardiovascular parameters under those three conditions demonstrated that when the AABP was assisting the system, parameters under CHHF conditions went back to normal healthy values, indicating the AABP's effectiveness as CHHF therapy. Our preliminary results indicate that it is feasible to use the AABP as a LVAD. The next steps include long-term in vivo experiments.

Centrifugal blood pump for temporary ventricular assist deviceswith low priming and ceramic bearings

A new model of centrifugal blood pump for temporaryventricular assist devices has been developed andevaluated. The design of the device is based on centrifugalpumping principles and the usage of ceramic bearings,resulting in a pump with reduced priming (35 ± 2 mL) thatcan be applied for up to 30 days. Computational fluiddynamic (CFD) analysis is an efficient tool to optimizeflow path geometry, maximize hydraulic performance, andminimize shear stress, consequently decreasing hemolysis.Initial studies were conducted by analyzing flow behaviorwith different impellers, aiming to determine the bestimpeller design.After CFD studies, rapid prototyping technologywas used for production of pump prototypes withthree different impellers. In vitro experiments were performedwith those prototypes, using a mock loop systemcomposed of Tygon tubes, oxygenator, digital flow meter,pressure monitor, electronic driver, and adjustable clampfor flow control, filled with a solution (1/3 water, 1/3 glycerin,1/3 alcohol) simulating blood viscosity and density.Flow-versus-pressure curves were obtained for rotationalspeeds of 1000, 1500, 2000, 2500, and 3000 rpm.As the nextstep, the CFD analysis and hydrodynamic performanceresults will be compared with the results of flow visualizationstudies and hemolysis tests.

Study of a centrifugal blood pump in a mock loop system

Abstract: An implantable centrifugal blood pump (ICBP)is being developed to be used as a ventricular assist device(VAD) in patients with severe cardiovascular diseases.TheICBP system is composed of a centrifugal pump, a motor, acontroller, and a power supply. The electricity source providespower to the controller and to a motor that moves thepump’s rotor through magnetic coupling. The centrifugalpump is composed of four parts: external conical house,external base, impeller, and impeller base.The rotor is supportedby a pivot bearing system, and its impeller base isresponsible for sheltering four permanent magnets. Ahybrid cardiovascular simulator (HCS) was used to evaluatethe ICBP’s performance. A heart failure (HF) (whenthe heart increases beat frequency to compensate fordecrease in blood flow) was simulated in the HCS. Themain objective of this work is to analyze changes in physiologicalparameters such as cardiac output, blood pressure,and heart rate in three situations: healthy heart, HF, andHF with left circulatory assistance by ICBP. The resultsshowed that parameters such as aortic pressure and cardiacoutput affected by the HF situation returned to normalvalues when the ICBP was connected to the HCS. Inconclusion, the test results showed satisfactory performancefor the ICBP as a VAD. Key Words: Ventricularassist device—Centrifugal blood pump—Cardiovascularsimulator.

Introductory tests to in vivo evaluation: magnetic coupling influence in motor controller.

An implantable centrifugal blood pump has been developed with original features for a ventricle assist device (VAD). This pump is part of a multicenter and international study with objective to offer simple, affordable, and reliable devices to developing countries. Previous computational fluid dynamics investigations were performed followed by prototyping and in vitro tests. Also, previous blood tests for assessment of hemolysis showed mean normalized index of hemolysis (NIH) results of 0.0054 ± 2.46 × 10⁻³ mg/100 L (at 5 L/min and 100 mm Hg). To precede in vivo evaluation, measurements of magnetic coupling interference and enhancements of actuator control were necessary. Methodology was based on the study of two different work situations (1 and 2) studied with two different types of motors (A and B). Situation 1 is when the rotor of pump is closest to the motor and situation 2 its opposite. Torque and mechanical power were collected with a dynamometer (80 g/cm) and then plotted and compared for two situations and both motors. The results showed that motor A has better mechanical behavior and less influence of coupling. Results for situation 1 showed that it is more often under magnetic coupling influence than situation 2. The studies lead to the conclusion that motor A is the best option for in vivo studies as it has less influence of magnetic coupling in both situations.

Implantable centrifugal blood pump with dual impeller and double pivot bearing system: electromechanical actuator, prototyping, and anatomical studies.

An implantable centrifugal blood pump has been developed with original features for a left ventricular assist device. This pump is part of a multicenter and international study with the objective to offer simple, affordable, and reliable devices to developing countries. Previous computational fluid dynamics investigations and wear evaluation in bearing system were performed followed by prototyping and in vitro tests. In addition, previous blood tests for assessment of normalized index of hemolysis show results of 0.0054±2.46 × 10⁻³ mg/100 L. An electromechanical actuator was tested in order to define the best motor topology and controller configuration. Three different topologies of brushless direct current motor (BLDCM) were analyzed. An electronic driver was tested in different situations, and the BLDCM had its mechanical properties tested in a dynamometer. Prior to evaluation of performance during in vivo animal studies, anatomical studies were necessary to achieve the best configuration and cannulation for left ventricular assistance. The results were considered satisfactory, and the next step is to test the performance of the device in vivo.

A new model of centrifugal blood pump for cardiopulmonary bypass: design improvement, performance, and hemolysis tests.

A new model of blood pump for cardiopulmonary bypass (CPB) application has been developed and evaluated in our laboratories. Inside the pump housing is a spiral impeller that is conically shaped and has threads on its surface. Worm gears provide an axial motion of the blood column. Rotational motion of the conical shape generates a centrifugal pumping effect and improves pumping performance. One annular magnet with six poles is inside the impeller, providing magnetic coupling to a brushless direct current motor. In order to study the pumping performance, a mock loop system was assembled. Mock loop was composed of Tygon tubes (Saint-Gobain Corporation, Courbevoie, France), oxygenator, digital flowmeter, pressure monitor, electronic driver, and adjustable clamp for flow control. Experiments were performed on six prototypes with small differences in their design. Each prototype was tested and flow and pressure data were obtained for rotational speed of 1000, 1500, 2000, 2500, and 3000 rpm. Hemolysis was studied using pumps with different internal gap sizes (1.35, 1.45, 1.55, and 1.7 mm). Hemolysis tests simulated CPB application with flow rate of 5 L/min against total pressure head of 350 mm Hg. The results from six prototypes were satisfactory, compared to the results from the literature. However, prototype #6 showed the best results. Best hemolysis results were observed with a gap of 1.45 mm, and showed a normalized index of hemolysis of 0.013 g/100 L. When combined, axial and centrifugal pumping principles produce better hydrodynamic performance without increasing hemolysis.

Cardiovascular simulator improvement: pressure versus volume loop assessment.

This article presents improvement on a physical cardiovascular simulator (PCS) system. Intraventricular pressure versus intraventricular volume (PxV) loop was obtained to evaluate performance of a pulsatile chamber mimicking the human left ventricle. PxV loop shows heart contractility and is normally used to evaluate heart performance. In many heart diseases, the stroke volume decreases because of low heart contractility. This pathological situation must be simulated by the PCS in order to evaluate the assistance provided by a ventricular assist device (VAD). The PCS system is automatically controlled by a computer and is an auxiliary tool for VAD control strategies development. This PCS system is according to a Windkessel model where lumped parameters are used for cardiovascular system analysis. Peripheral resistance, arteries compliance, and fluid inertance are simulated. The simulator has an actuator with a roller screw and brushless direct current motor, and the stroke volume is regulated by the actuator displacement. Internal pressure and volume measurements are monitored to obtain the PxV loop. Left chamber internal pressure is directly obtained by pressure transducer; however, internal volume has been obtained indirectly by using a linear variable differential transformer, which senses the diaphragm displacement. Correlations between the internal volume and diaphragm position are made. LabVIEW integrates these signals and shows the pressure versus internal volume loop. The results that have been obtained from the PCS system show PxV loops at different ventricle elastances, making possible the simulation of pathological situations. A preliminary test with a pulsatile VAD attached to PCS system was made.

Specification of supervisory control systems for ventricular assist devices.

One of the most important recent improvements in cardiology is the use of ventricular assist devices (VADs) to help patients with severe heart diseases, especially when they are indicated to heart transplantation. The Institute Dante Pazzanese of Cardiology has been developing an implantable centrifugal blood pump that will be able to help a sick human heart to keep blood flow and pressure at physiological levels. This device will be used as a totally or partially implantable VAD. Therefore, an improvement on device performance is important for the betterment of the level of interaction with patient's behavior or conditions. But some failures may occur if the device's pumping control does not follow the changes in patient's behavior or conditions. The VAD control system must consider tolerance to faults and have a dynamic adaptation according to patient's cardiovascular system changes, and also must attend to changes in patient conditions, behavior, or comportments. This work proposes an application of the mechatronic approach to this class of devices based on advanced techniques for control, instrumentation, and automation to define a method for developing a hierarchical supervisory control system that is able to perform VAD control dynamically, automatically, and securely. For this methodology, we used concepts based on Bayesian network for patients' diagnoses, Petri nets to generate a VAD control algorithm, and Safety Instrumented Systems to ensure VAD system security. Applying these concepts, a VAD control system is being built for method effectiveness confirmation.

Cardiovascular simulator improvement: pressure versus volume loop assessment

This article presents improvement on a physical cardiovascular simulator (PCS) system. Intraventricular pressure versus intraventricular volume (PxV) loop was obtained to evaluate performance of a pulsatile chambermimicking the human left ventricle. PxV loop shows heart contractility and is normally used to evaluate heartperformance. In many heart diseases, the stroke volume decreases because of low heart contractility.This pathologicalsituation must be simulated by the PCS in order to evaluate the assistance provided by a ventricular assistdevice (VAD).The PCS system is automatically controlled by a computer and is an auxiliary tool for VAD controlstrategies development. This PCS system is according to a Windkessel model where lumped parameters are used for cardiovascular system analysis. Peripheral resistance, arteriescompliance, and fluid inertance are simulated.The simulator has an actuator with a roller screw and brushlessdirect current motor, and the stroke volume is regulated by the actuator displacement. Internal pressure and volume measurements are monitored to obtain the PxV loop. Left chamber internal pressure is directly obtained by pressure transducer; however, internal volume has been obtained indirectly by using a linear variable differential transformer, which senses the diaphragm displacement. Correlationsbetween the internal volume and diaphragm position are made. LabVIEW integrates these signals and shows the pressure versus internal volume loop. The results that have been obtained from the PCS system show PxV loops at different ventricle elastances, makingpossible the simulation of pathological situations. A preliminary test with a pulsatile VAD attached to PCS systemwas made.

Specification of supervisory control systems for ventricular assist devices

One of the most important recent improvements in cardiology is the use of ventricular assist devices (VADs) to help patients with severe heart diseases, especially when they are indicated to heart transplantation.TheInstitute Dante Pazzanese of Cardiology has been developing an implantable centrifugal blood pump that will beable to help a sick human heart to keep blood flow and pressure at physiological levels. This device will be used asa totally or partially implantable VAD. Therefore, an improvement on device performance is important for thebetterment of the level of interaction with patient’s behavior or conditions. But some failures may occur if the device’s pumping control does not follow the changes in patient’s behavior or conditions. The VAD control system must consider tolerance to faults and have a dynamic adaptation according to patient’s cardiovascular system changes, and also must attend to changes in patient conditions, behavior, or comportments. This work proposes anapplication of the mechatronic approach to this class of devices based on advanced techniques for control, instrumentation, and automation to define a method for developinga hierarchical supervisory control system that is able to perform VAD control dynamically, automatically, andsecurely. For this methodology, we used concepts based on Bayesian network for patients’ diagnoses, Petri nets to generate a VAD control algorithm, and Safety Instrumented Systems to ensure VAD system security. Applying theseconcepts, a VAD control system is being built for method effectiveness confirmation.