Simulation of dilated heart failure with continuous flow circulatory support

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/ without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept of extremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery. © 2014 Wang et al

Balancing the ventricular outputs of pulsatile total artificial hearts

Background: Maintaining balanced left and right cardiac outputs in a total artificial heart (TAH) is challenging due to the need for continuous adaptation to changing hemodynamic conditions. Proper balance in ventricular outputs of the left and right ventricles requires a preload-sensitive response and mechanisms to address the higher volumetric efficiency of the right ventricle. Methods: This review provides a comprehensive overview of various methods used to balance left and right ventricular outputs in pulsatile total artificial hearts, categorized based on their actuation mechanism. Results:Reported strategies include incorporating compliant materials and/or air cushions inside the ventricles, employing active control mechanisms to regulate ventricular filling state, and utilizing various shunts (such as hydraulic or intra-atrial shunts). Furthermore, reducing right ventricular stroke volume compared to the left often serves to balance the ventricular outputs. Individually controlled actuation of both ventricles in a pulsatile TAH seems to be the simplest and most effective way to achieve proper preload sensitivity and left–right output balance. Pneumatically actuated TAHs have the advantage to respond passively to preload changes. Conclusion: Therefore, a pneumatic TAH that comprises two individually actuated ventricles appears to be a more desirable option—both in terms of simplicity and efficacy—to respond to changing hemodynamic conditions.</p

Rotary pump speed modulation to produce pulsatile flow and ventricular volume unloading.

Background: Continuous-flow (CF) left ventricular assist devices (LVADs) have gained widespread clinical acceptance as a treatment option for advanced heart failure (HF); however, they have also been associated with an increased risk of adverse events, including gastrointestinal bleeding, aortic insufficiency, and hemorrhagic stroke. It has been hypothesized that the increase in adverse event incidence may be due in part to diminished vascular pulsatility and high shear stress when CF-LVADs are operated at fixed speeds. Previous studies have shown that pump speed modulation generates greater levels of pulsatility in rotary pumps than when operated at fixed speeds. The objective of this study was to characterize the hemodynamic and pump performance of LVADs operated with a low-frequency asynchronous pump speed modulation algorithm in a chronic healthy bovine model with partial VAD support. Materials and Methods: Clinical-grade LVAD with aortic (HeartWare HVAD, n=3) or transaortic (proprietary VADx, n=4) outflow were implanted into chronic (30-day) healthy male Jersey calves (60-110 kg). An asynchronous pump speed modulation algorithm (frequency = 20 bpm, amplitude = 2500-4000 RPM for HVAD or 11000-19000 RPM for VADx) was implemented by controlling pump current. Hemodynamic measurements (pressures, flows) were recorded throughout the study duration (30s epochs collected hourly at 400Hz), echocardiographic data was recorded during the implant, weekly, and at terminal, and blood laboratory measurements were regularly collected throughout the study. All data were analyzed to characterize aortic pulsatility, LV unloading, blood damage, and device power usage. Statistical analysis was performed to determine significance between fixed and pump speed modulation operating conditions. Results and Discussion: Two HVAD and four VADx animals achieved the 30-day study endpoint. Due to surgical complications, one animal died intraoperatively. Both HVAD devices maintained asynchronous modulation for the full study duration with mean high and low speeds of 4000 RPM and 2500 RPM, respectively. Two of the four VADx devices maintained asynchronous modulation at average high and low speeds of 17238 RPM and 11333 RPM over the 30-day study; however, the other two VADx devices operated at fixed pump speed for 1 and 2 days, respectively, due to unforeseen controller malfunctions, which were corrected to restore asynchronous modulation. Near-physiologic aortic pulse pressure for HVAD (45±4 mmHg) and VADx (46±9 mmHg) was demonstrated. HVAD and VADx with asynchronous modulation reduced stroke volume by 27% and 23%, respectively. HVAD (n=2) and VADx (n=3) maintained plasma free hemoglobin (pfHb) less than 40 mg/dL for the entire study duration while one VADx had pfHb \u3e 40 mg/dL for a period of 3 days, which resolved. Asynchronous modulation increased power consumption with HVAD (25%) and VADx (6%) compared to fixed speed operation. Conclusion: This study demonstrated asynchronous modulation of HVAD and VADx maintained near-physiologic pulsatility and LV unloading at the expense of minimal hemolysis and increased power consumption in the partial VAD support model. Future studies in clinically-relevant heart failure models warrant further investigation

Pathophysiology in Heart Failure

Heart failure syndrome is defined as the inability of the heart to deliver adequate blood to the body to meet end-organ metabolic needs and oxygenation at rest or during mild exercise. Myocardial dysfunction can be defined as systolic and/or diastolic, acute or chronic, compensated or uncompensated, or uni- or biventricular. Several counterregulatory mechanisms are activated depending on the duration of the heart failure. Neurohormonal reflexes such as sympathetic adrenergic system, renin-angiotensin cascade, and renal and peripheral alterations attempt to restore both cardiac output and end-tissue perfusion. An adequate stroke volume cannot be ejected from the left ventricle, which shifts the whole pressure-volume relationship to the right (systolic failure). Adequate filling cannot be realized due to diastolic stiffness, which shifts the diastolic pressure-volume curve upward without affecting the systolic pressure-volume curve (diastolic failure). Left ventricular heart failure is the dominant picture of heart failure syndrome, but the right heart can develop isolated failure as well. Biventricular failure is mostly an end-stage clinical situation of the heart failure syndrome. More recently, the rise in the incidence of right ventricular failure can be seen after the implantation of a left ventricular assist device. This chapter clarifies and presents pathophysiologic alterations in heart failure syndrome

A Concept for Direct Control of Rotary Blood Pump Speed by Inlet Pressure

Heart failure remains a major health problem for the world. Heart transplantation is the most effective treatment for end stage heart failure. A major problem with heart transplantation is finding adequate numbers of appropriate donors. The lack of donor numbers in the world creates a significant clinical need for blood pumping devices. The ability of ventricular assist devices to relieve the consequences of less than terminal heart failure further creates a need for assist therapy. Current new ventricular assist devices are built around continuous flow technology. These nonpulsatile assist devices have had major clinical success in relieving symptoms and increasing patient survival. However they have a control issue as opposed the first generation pulsatile Ventricular Assist Devices (VADs) in that their output is sensitive to pressure difference, not primarily to inlet pressure. We have developed a rotodynamic blood pump speed management concept that results in a pump that responds to inlet pressure in a Starling law-like manner without active electronic controls or pressure sensors. The long term goal of this project is to develop a VAD system which responds as the natural human heart does. The pump speed is controlled by an adjunct electromechanical inlet conduit. The inlet conduit has 2 integrated cylinders. The inner cylinder is the blood flow pathway, and is flexible in order to expand/collapse in response to inlet blood pressure. The outer cylinder is used as the coil of a tank circuit. There is also a ferrofluid reservoir which is connected to the space between the 2 cylinders. The majority of ferrofluid is in the reservoir when inlet pressure is high, but ferrofluid flows into the core of the coil when inlet pressure is low. The inductance of the coil varies in response to the volume of the ferrofluid within the core. Therefore the natural frequency of the tank circuit varies and the impedance of the tank circuit changes. The control circuit is connected in series with the motor leads. Thus the voltag

A Concept for Direct Control of Rotary Blood Pump Speed by Inlet Pressure

Heart failure remains a major health problem for the world. Heart transplantation is the most effective treatment for end stage heart failure. A major problem with heart transplantation is finding adequate numbers of appropriate donors. The lack of donor numbers in the world creates a significant clinical need for blood pumping devices. The ability of ventricular assist devices to relieve the consequences of less than terminal heart failure further creates a need for assist therapy. Current new ventricular assist devices are built around continuous flow technology. These nonpulsatile assist devices have had major clinical success in relieving symptoms and increasing patient survival. However they have a control issue as opposed the first generation pulsatile Ventricular Assist Devices (VADs) in that their output is sensitive to pressure difference, not primarily to inlet pressure. We have developed a rotodynamic blood pump speed management concept that results in a pump that responds to inlet pressure in a Starling law-like manner without active electronic controls or pressure sensors. The long term goal of this project is to develop a VAD system which responds as the natural human heart does. The pump speed is controlled by an adjunct electromechanical inlet conduit. The inlet conduit has 2 integrated cylinders. The inner cylinder is the blood flow pathway, and is flexible in order to expand/collapse in response to inlet blood pressure. The outer cylinder is used as the coil of a tank circuit. There is also a ferrofluid reservoir which is connected to the space between the 2 cylinders. The majority of ferrofluid is in the reservoir when inlet pressure is high, but ferrofluid flows into the core of the coil when inlet pressure is low. The inductance of the coil varies in response to the volume of the ferrofluid within the core. Therefore the natural frequency of the tank circuit varies and the impedance of the tank circuit changes. The control circuit is connected in series with the motor leads. Thus the voltag

FRAILTY IN PATIENTS UNDERGOING LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Heart failure is a progressive condition that affects over 5.7 million Americans and costs associated with heart failure account for 2-3 % of the national health care budget. The high rates of morbidity and mortality along with increased costs from readmissions associated with advanced heart failure have led to the exploration of advanced treatments such as left ventricular assist devices (LVADs). LVADS have demonstrated morbidity and mortality benefit but cost remains extensive with costs per quality-adjusted years \u3e $400,000. With this in mind, it is important to identify those who are most likely to benefit from an LVAD to avoid unfavorable outcomes and cost. Although general guidelines and criteria for patient eligibility have been established, choosing patients for LVAD implantation remains challenging. A new focus on patient selection involves the presence of frailty. While frailty has been studied in the elderly population and in patients undergoing cardiac surgery, frailty in patients undergoing left ventricular assist device (LVAD) remains controversial. The purpose of this dissertation was to examine measures of frailty in patients undergoing LVAD implantation. The specific aims of this dissertation were to: (1) identify a feasible frailty measure in adults with end-stage heart failure who underwent LVAD implantation by testing the hypothesis that frailty would predict 30 day rehospitalization rates using Fried’s criteria, Short Physical Performance Battery test, handgrip strength, serum albumin and six minute walk test (2) Determine whether frailty measures improve 3 months post LVAD implantation (3) compare sensitivity of these three measures to change in frailty. Surgical approaches, including heart transplantation and LVAD implantation, for patients with end-stage heart failure was discussed in this dissertation. Data from two subsets of participants who underwent LVADS at the University of Kentucky between 2014 and 2017 were included in the analysis for this dissertation. In the first study, we found that none of the measures are good predictors of frailty in patients with advanced heart failure who undergo LVAD implantation. Handgrip was the only marker of frailty that predicted 30 day readmission but the relationship was a negative association. In the second study, six-minute walk and low serum albumin levels reflect short-term improvement in frailty. These simple measures may be used to determine those patients who are responsive to LVAD implantation. The findings of these studies filled some gaps in our understanding of markers of frailty in patients undergoing LVADs. We gained a better understanding of which markers of frailty are likely to improve in most people after LVAD implantation and thus frailty should not preclude candidate selection for an LVAD. Subsequently, more research is needed to investigate these markers and outcomes

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties

Laboratory Development of a Self-Powered Fontan for Treatment of Congenital Heart Disease

Around 8% of all newborns with a Congenital Heart Defect (CHD) have only a single functioning ventricle. The Fontan operation has served as a palliation for this anomaly for decades, but the surgery entails multiple complications and survival rate is less than 50% by adulthood. A rapidly testable novel alternative is proposed by creating a bifurcating graft, or Injection Jet Shunt (IJS), used to “entrain” the pulmonary flow and thus provide assistance while reducing the caval pressure. A benchtop Mock Flow Loop (MFL) is configured to validate this hypothesis. The MFL is based on a Lumped-Parameter Model (LPM) of the Fontan circulation and is comprised of upper and lower systemic as well as left and right pulmonary compartments. Needle valves are used to accurately replicate vascular resistance (R) while compliance chambers are used to mimic vascular compliance values (C). The Fontan MFL is driven with cardiac pulsatility provided by a Harvard Apparatus medical pump. Patient-specific models of the centerpiece of the MFL along with the grafts (IJS) are produced via 3D printing. Baseline values are validated against patient-specific waveforms. Flow and pressure sensor data at specific points in the MFL are acquired via a National Instruments multichannel data acquisition board and processed using LabView. Several IJS nozzle diameters are tested to validate the hypothesis and optimize the improvement