Francesco Moscato

Left ventricle load impedance control by apical VAD can help heart recovery and patient perfusion: a numerical study.

The aim of this work is to investigate the dependence between left ventricular load impedance control by an apical ventricular assist device (VAD) and the consequent benefits for pathological heart recovery. A pathological left ventricle with 34% contractility has been simulated in the assisted and nonassisted conditions. By means of an extended Kalman filter, left ventricular pressure-volume loops have been partially estimated and ventricular as well as circulatory quantities inferred. The heart operation mode, based on cardiac energetic criteria, is imposed by controlling the VAD filling phase. In the assisted condition, results show that the left ventricle end-diastolic volume, left atrial pressure, and wall stress all decrease; stroke volume, ejection fraction, ventricular efficiency, aortic pressure, and cardiac output all increase. Benefits are also evident for the right ventricle and systemic and pulmonary circulation. The strategy outlined in this work also shows that good results for heart recovery are achievable and a possible way to improve the functional properties of commercial pulsatile VADs.

Left Ventricle Afterload Impedance Control by an Axial Flow Ventricular Assist Device: A Potential Tool for Ventricular Recovery

Ventricular assist devices (VADs) are increasingly used for supporting blood circulation in heart failure patients. To protect or even to restore the myocardial function, a defined loading of the ventricle for training would be important. Therefore, a VAD control strategy was developed that provides an explicitly definable loading condition for the failing ventricle. A mathematical model of the cardiovascular system with an axial flow VAD was used to test the control strategy in the presence of a failing left ventricle, slight physical activity, and a recovering scenario. Furthermore, the proposed control strategy was compared to a conventional constant speed mode during hemodynamic changes (reduced venous return and arterial vasoconstriction). The physiological benefit of the control strategy was manifested by a large increase in the ventricular Frank-Starling reserve and by restoration of normal hemodynamics (5.1 L/min cardiac output at a left atrial pressure of 10 mmHg vs. 4.2 L/min at 21 mmHg in the unassisted case). The control strategy automatically reduced the pump speed in response to reduced venous return and kept the pump flow independent of the vasoconstriction condition. Most importantly, the ventricular load was kept stable within 1%, compared to a change of 75% for the constant speed. As a key feature, the proposed control strategy provides a defined and adjustable load to the failing ventricle by an automatic regulation of the VAD speed and allows a controlled training of the myocardium. This, in turn, may represent a potential additional tool to increase the number of patients showing recovery.

Continuous assessment of cardiac function during rotary blood pump support: A contractility index derived from pump flow

BACKGROUND The clinical application of rotary blood pumps (RBPs) for bridge-to-recovery and destination therapy has focused interest on the remaining contractile function of the heart and its course. This study reports a method to determine contractility that uses readily measured variables of the RBP. METHOD The proposed index (I(Q)) is defined as the slope of a linear regression between the maximum derivative of the pump flow and its peak-to-peak value. I(Q) was compared with the maximal derivative of ventricular pressure (dP/dt(max)) vs end-diastolic volume (EDV) and the pre-load-recruitable stroke work. All indices were evaluated using computer simulations and animal experiments. For in vivo studies, a MicroMed-DeBakey ventricular assist device (VAD) was implanted in 7 healthy sheep. Ventricular contractility was examined under normal conditions and after pharmacologic intervention. For the computer simulation, variations of ventricular contractility, ventricular pre-load and after-load, and pump speeds were studied. RESULTS In vivo and computer simulations showed the I(Q) index to be sensitive to changes of cardiac contractility, similar to other classic indices. For reduced cardiac contractility, it decreased to 9.3 +/- 3.9 (s(-1)) vs 15.3 +/- 4.0 (s(-1)) in the control condition (in vivo experiments). The I(Q) index was only marginally influenced by pre-load and after-load changes: a variation of 7.0% +/- 8.9% and 1.3% +/- 7.1%, respectively, was observed in computer simulations. CONCLUSIONS The I(Q) index, which can be derived from pump data only, is a useful parameter for continuous monitoring of the cardiac contractility in patients with RBP support.

Development of a Pump Flow Estimator for Rotary Blood Pumps to Enhance Monitoring of Ventricular Function

Estimation of instantaneous flow in rotary blood pumps (RBPs) is important for monitoring the interaction between heart and pump and eventually the ventricular function. Our group has reported an algorithm to derive ventricular contractility based on the maximum time derivative (dQ/dt(max) as a substitute for ventricular dP/dt(max) ) and pulsatility of measured flow signals. However, in RBPs used clinically, flow is estimated with a bandwidth too low to determine dQ/dt(max) in the case of improving heart function. The aim of this study was to develop a flow estimator for a centrifugal pump with bandwidth sufficient to provide noninvasive cardiac diagnostics. The new estimator is based on both static and dynamic properties of the brushless DC motor. An in vitro setup was employed to identify the performance of pump and motor up to 20 Hz. The algorithm was validated using physiological ventricular and arterial pressure waveforms in a mock loop which simulated different contractilities (dP/dt(max) 600 to 2300 mm Hg/s), pump speeds (2 to 4 krpm), and fluid viscosities (2 to 4 mPa·s). The mathematically estimated pump flow data were then compared to the datasets measured in the mock loop for different variable combinations (flow ranging from 2.5 to 7 L/min, pulsatility from 3.5 to 6 L/min, dQ/dt(max) from 15 to 60 L/min/s). Transfer function analysis showed that the developed algorithm could estimate the flow waveform with a bandwidth up to 15 Hz (±2 dB). The mean difference between the estimated and measured average flows was +0.06 ± 0.31 L/min and for the flow pulsatilities -0.27 ± 0.2 L/min. Detection of dQ/dt(max) was possible up to a dP/dt(max) level of 2300 mm Hg/s. In conclusion, a flow estimator with sufficient frequency bandwidth and accuracy to allow determination of changes in ventricular contractility even in the case of improving heart function was developed.

Safety and efficacy of cardiac rehabilitation for patients with continuous flow left ventricular assist devices

Background Despite the increasing use of left ventricular assist devices (LVADs) in terminal heart failure, cardiac rehabilitation protocols have not yet been documented in larger LVAD patient cohorts. The aim of this study was to investigate safety and efficacy of exercise training during a rehabilitation programme after post-operative discharge of LVAD patients. Methods Rehabilitation data obtained between 2010–2012 from 41 LVAD patients (mean age 54.8 ± 11.6 years; 20% female) were retrospectively analysed. The exercise protocol consisted of strength exercises for lower limbs, bicycle ergometry, walking and gymnastics. The numbers of training sessions, their duration and intensity as well as adverse events were documented. Spiroergometry was performed at least once and twice in a subgroup of 15 patients (at the beginning and end of rehabilitation). Results Rehabilitation started 48 ± 38 days post LVAD implantation with an average duration of 32 ± 6 days. An increase in exercise capacity was observed. Duration (19 ± 4 vs 14 ± 2 min, p < 0.001) and intensity of bicycle ergometry increased (module number 6.2 ± 2.8 vs 2.0 ± 1.9, p < 0.001) as well as muscular strength all muscle groups trained (e.g. 33.6 ± 15.2 vs 26.6 ± 11.9 kg at the leg press, p = 0.002). Spiroergometry revealed an increase of maximal oxygen consumption (14.5 ± 5.2 vs 11.3 ± 4.1 ml/min/kg, p = 0.007) in the subgroup that underwent two examinations. In the whole population the average increase was lower (12.81 ± 4.35 ml/min/kg). One training-related adverse event (non-sustained ventricular tachycardia) was observed. Conclusion Exercise training for LVAD patient as part of a multidisciplinary rehabilitation programme is effective and safe. This warrants the broad application of exercise training after LVAD implantation.

Hybrid test bench for evaluation of any device related to mechanical cardiac assistance.

Hydraulic mock circulatory systems have low flexibility to allow tests of different cardiovascular devices and low precision when a reference model must be reproduced. In this paper a new bench is described. It combines the computer model of the environment in which the device will operate and the electro-hydraulic interfaces by which device and computer are connected. A models library provided with basic functions allows implementing many layouts of the bench, which in turn depend both on the device properties and the desired experiment. In case of an apical LVAD evaluation, the bench can reproduce right and left ventricles, pulmonary and systemic circulations, inlet and outlet LVAD cannulas. An interface forces the instantaneous calculated flow at the VAD input and feeds back the measured pressure to the computer; another interface works in a similar -but complementary- way at the VAD output. The paper focuses on the operating principle of the electro hydraulic interfaces which represent a relevant component of the bench, on the RT-Linux-based software architecture, on the models of the basic elements of the bench. A patent is under preparation. At the moment, only a portion of the bench has been developed. It consists of a piston-cylinder mechanism, which mimics the elastance-based mechanism of a natural ventricle, and a hydraulic circuit representing the arterial load according to a modified windkessel model and the venous return according to the Guytons model. The pump is driven by a real-time simulation of the cardiovascular system. This preliminary layout allowed testing the piston-cylinder mechanism, its control, and the software. This electro-hydraulic interface has been used to reproduce a pulsatile pump working in different modes. The hybrid model approach can support the development of new cardiac assist devices from their computer model to their manufacture.

Assessment of Aortic Valve Opening During Rotary Blood Pump Support Using Pump Signals

During left ventricular support by rotary blood pumps (RBPs), the biomechanics of the aortic valve (AV) are altered, potentially leading to adverse events like commissural fusion, valve insufficiency, or thrombus formation. To avoid these events, assessment of AV opening and consequent adaptation of pump speed seem important. Additionally, this information provides insight into the heart-pump interaction. The aim of this study was to develop a method to assess AV opening from the pump flow signal. Data from a numerical model of the cardiovascular system and animal experiments with an RBP were employed to detect the AV opening from the flow waveform under different hemodynamic conditions. Three features calculated from the pump flow waveform were used to classify the state of the AV: skewness, kurtosis, and crest factor. Three different classification algorithms were applied to determine the state of the AV based on these features. In the model data, the best classifier resulted in a percentage of correctly identified beats with a closed AV (specificity) of 99.9%. The percentage of correctly identified beats with an open AV (sensitivity) was 99.5%. In the animal experiments, specificity was 86.8% and sensitivity reached 96.5%. In conclusion, a method to detect AV opening independently from preload, afterload, heart rate, contractility, and degree of support was developed. This algorithm makes the evaluation of the state of the AV possible from pump data only, allowing pump speed adjustment for a frequent opening of the AV and providing information about the interaction of the native heart with the RBP.

Rapid induction of mild therapeutic hypothermia by extracorporeal veno-venous blood cooling in humans

AIM Mild therapeutic hypothermia is beneficial in patients successfully resuscitated from non-traumatic out-of-hospital cardiac arrest. The effect of fast induction of hypothermia in these patients remains to be investigated. The aim of this study was to evaluate the efficacy and safety of extracorporeal veno-venous blood cooling in humans successfully resuscitated from cardiac arrest. METHODS We performed an interventional study in patients after successful resuscitation from cardiac arrest admitted to the emergency department of a tertiary care centre. The extracorporeal veno-venous circulation was established via a percutaneously introduced double lumen dialysis catheter in the femoral vein, and a tubing circuit and heat exchanger. A paediatric cardiopulmonary bypass roller pump and a heater-cooler system were used to circulate the blood. Main outcome measures were feasibility, efficacy, and safety. RESULTS We included eight consecutive cardiac arrest patients with a median oesophageal temperature of 35.9°C (interquartile range 34.9-37.0). A median time of 8 min elapsed (interquartile range 5-15 min) to reach oesophageal temperatures below 34°C, which reflects a cooling rate of 12.2°C/h (interquartile range 10.8°C/h to 14.1°C/h). The predefined target temperature of 33.0°C was reached after 14 min (interquartile range 8-21 min). No device or method related adverse events were reported. CONCLUSION Extracorporeal veno-venous blood cooling is a feasible, safe, and very fast approach for induction of mild therapeutic hypothermia in patients successfully resuscitated from cardiac arrest.

A modified elastance model to control mock ventricles in real-time: numerical and experimental validation.

This article describes an elastance-based mock ventricle able to reproduce the correct ventricular pressure-volume relationship and its correct interaction with the hydraulic circuit connected to it. A real-time control of the mock ventricle was obtained by a new left ventricular mathematical model including resistive and inductive terms added to the classical Suga-Sagawa elastance model throughout the whole cardiac cycle. A valved piston pump was used to mimic the left ventricle. The pressure measured into the pump chamber was fed back into the mathematical model and the calculated reference left ventricular volume was used to drive the piston. Results show that the classical model is very sensitive to pressure disturbances, especially during the filling phase, while the modified model is able to filter out the oscillations thus eliminating their detrimental effects. The presented model is thus suitable to control mock ventricles in real-time, where sudden pressure disturbances represent a key issue and are not negligible. This real-time controlled mock ventricle is able to reproduce the elastance mechanism of a natural ventricle by mimicking its preload (mean atrial pressure) and afterload (mean aortic pressure) sensitivity, i.e., the Starling law. Therefore, it can be used for designing and testing cardiovascular prostheses due to its capability to reproduce the correct ventricle-vascular system interaction.

Evaluation of Left Ventricular Relaxation in Rotary Blood Pump Recipients Using the Pump Flow Waveform: A Simulation Study

In heart failure, diastolic dysfunction is responsible for about 50% of the cases, with higher prevalence in women and elderly persons and contributing similarly to mortality as systolic dysfunction. Whereas the cardiac systolic diagnostics in ventricular assist device patients from pump parameters have been investigated by several groups, the diastolic behavior has been barely discussed. This study focuses on the determination of ventricular relaxation during early diastole in rotary blood pump (RBP) recipients. In conventional cardiology, relaxation is usually evaluated by the minimum rate and the time constant of left ventricular pressure decrease, dP/dt(min) and τ(P) . Two new analogous indices derived from the pump flow waveform were investigated in this study: the minimum rate and the time constant of pump flow decrease, dQ/dt(min) and τ(Q) . The correspondence between the indices was investigated in a numerical simulation of the assisted circulation for different ventricular relaxation states (τ(P) ranging from 24 to 68 ms) and two RBP models characterized by linear and nonlinear pressure-flow characteristics. dQ/dt(min) and τ(Q) always correlated with the dP/dt(min) and τ(P) , respectively (r>0.97). These relationships were influenced by the nonlinear pump characteristics during partial support and by the pump speed during full support. To minimize these influences, simulation results suggest the evaluation of dQ/dt(min) and τ(Q) at a pump speed that corresponds to the borderline between partial and full support. In conclusion, at least in simulation, relaxation can be derived from pump data. This noninvasively accessible information could contribute to a continuous estimation of the remaining cardiac function and its eventual recovery.