Flow capabilities of arterial and drainage cannulae during venoarterial extracorporeal membrane oxygenation: A simulation model.

BACKGROUND: Large cannulae can increase cannula-related complications during venoarterial extracorporeal membrane oxygenation (VA ECMO). Conversely, the ability for small cannulae to provide adequate support is poorly understood. Therefore, we aimed to evaluate a range of cannula sizes and VA ECMO flow rates in a simulated patient under various disease states. METHODS: Arterial cannulae sizes between 13 and 21 Fr and drainage cannula sizes between 21 and 25 Fr were tested in a VA ECMO circuit connected to a mock circulation loop simulating a patient with severe left ventricular failure. Systemic and pulmonary hypertension, physiologically normal, and hypotension were simulated by varying systemic and pulmonary vascular resistances (SVR and PVR, respectively). All cannula combinations were evaluated against all combinations of SVR, PVR, and VA ECMO flow rates. RESULTS: A 15 Fr arterial cannula combined with a 21 Fr drainage cannula could provide >4 L/min of total flow and a mean arterial pressure of 81.1 mmHg. Changes in SVR produced marked changes to all measured parameters, while changes to PVR had minimal effect. Larger drainage cannulae only increased maximum circuit flow rates when combined with larger arterial cannulae. CONCLUSION: Smaller cannulae and lower flow rates could sufficiently support the simulated patient under various disease states. We found arterial cannula size and SVR to be key factors in determining the flow-delivering capabilities for any given VA ECMO circuit. Overall, our results challenge the notion that larger cannulae and high flows must be used to achieve adequate ECMO support.

Use of Sutureless Valve in Aortic Root Enlargement.

AIM: The small aortic annulus is a surgical challenge in patients undergoing aortic valve replacement which may lead to patient prosthesis mismatch. Management options include aortic root enlargement, aortic root replacement, and the use of sutureless valves. In this case series, we report our results with aortic root enlargement, sutureless valve implantation, and benchtop modelling of the radial forces exerted. METHODS: Five patients underwent aortic root enlargement and insertion of the Perceval valve as part of the management strategy to enlarge their effective orifice area. We further investigate this strategy with a benchtop model to quantify the radial forces exerted by the Perceval valve on the aortic annulus. Radial and hoop forces on the aortic annulus and inner ring of the Perceval valve were recorded using a Mylar force tester. RESULTS: Five female patients with native annulus between 18mm-20mm underwent root enlargement and insertion of a Perceval S valve. The postoperative course was uncomplicated for all patients except for one who required a permanent pacemaker insertion. Transvalvular pressure gradients remained low at up to 4 years of follow-up (12 mmHg-21 mmHg), with no evidence of paravalvular leak. Benchtop testing demonstrated radial forces exerted at the annulus in all-size Perceval S valves to be within physiological variables, whereas compressive forces required to deform the valves were supraphysiological. CONCLUSIONS: The deployment of a sutureless valve within a surgical enlarged aortic root is a feasible solution in patients with a small aortic root.

Smaller Return Cannula in Venoarterial Extracorporeal Membrane Oxygenation Does Not Increase Hemolysis: A Single-Center, Cohort Study.

The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin ( pf Hb). Moderate hemolysis is defined as having pf Hb 0.05-0.10 g/L and severe hemolysis as having pf Hb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs . 6; p = 0.39) and severe hemolysis (0 vs . 3; p = 0.27), nor was the pf Hb level significantly different at 4 hours (0.086 ± 0.096 vs . 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs . 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.

ECMO PAL: using deep neural networks for survival prediction in venoarterial extracorporeal membrane oxygenation.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a complex and high-risk life support modality used in severe cardiorespiratory failure. ECMO survival scores are used clinically for patient prognostication and outcomes risk adjustment. This study aims to create the first artificial intelligence (AI)-driven ECMO survival score to predict in-hospital mortality based on a large international patient cohort. METHODS: A deep neural network, ECMO Predictive Algorithm (ECMO PAL) was trained on a retrospective cohort of 18,167 patients from the international Extracorporeal Life Support Organisation (ELSO) registry (2017-2020), and performance was measured using fivefold cross-validation. External validation was performed on all adult registry patients from 2021 (N = 5015) and compared against existing prognostication scores: SAVE, Modified SAVE, and ECMO ACCEPTS for predicting in-hospital mortality. RESULTS: Mean age was 56.8 ± 15.1 years, with 66.7% of patients being male and 50.2% having a pre-ECMO cardiac arrest. Cross-validation demonstrated an inhospital mortality sensitivity and precision of 82.1 ± 0.2% and 77.6 ± 0.2%, respectively. Validation accuracy was only 2.8% lower than training accuracy, reducing from 75.5% to 72.7% [99% confidence interval (CI) 71.1-74.3%]. ECMO PAL accuracy outperformed the ECMO ACCEPTS (54.7%), SAVE (61.1%), and Modified SAVE (62%) scores. CONCLUSIONS: ECMO PAL is the first AI-powered ECMO survival score trained and validated on large international patient cohorts. ECMO PAL demonstrated high generalisability across ECMO regions and outperformed existing, widely used scores. Beyond ECMO, this study highlights how large international registry data can be leveraged for AI prognostication for complex critical care therapies.

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.

Impact of Concomitant Mitral Regurgitation on the Hemodynamic Indicators of Aortic Stenosis.

Background In patients with aortic stenosis (AS), the presence of mitral regurgitation (MR) can lead to underestimation of AS severity and worse clinical outcomes. The objective of this study was to characterize the magnitude of the effects of concomitant MR on hemodynamic indicators of AS severity using clinical data and a computational cardiovascular simulation. Methods and Results Echocardiographic data from 1427 patients with severe AS were used to inform a computational cardiovascular system model, and varying degrees of MR and AS were simulated. Hemodynamic data, including left ventricular and aortic pressure waveforms, were generated for all simulations. Simulated reduction in mean transaortic pressure gradient (MPG) associated with MR was then used to calculate the adjusted MPG in the clinical cohort. MR was present in 861 (60%) patients. Compared with patients without MR, patients with MR had a lower aortic-valve area (0.83±0.2 cm2 versus 0.75±0.2; P<0.001) and were more likely to have a low-gradient pattern (MPG <40 mm Hg) (45% versus 54%; P<0.001). Simulations showed that the presence of concomitant mild, moderate, and severe MR with AS was accompanied by a mean reduction in MPG of 10%, 29%, and 40%, respectively. For patients with MR, their calculated adjusted MPG was on average 24% higher than their MPG (52±22 versus 42±16 mm Hg). Of the 467 patients with low-gradient AS and MR, 240 (51%) would reclassify as high gradient based on their adjusted MPG. Conclusions Concomitant MR results in lower MPG and reduced forward flow compared with isolated AS. Careful quantitation of MR should be factored into the assessment of AS severity to mitigate for potential underestimation.

The effect of arterial cannula tip position on differential hypoxemia during venoarterial extracorporeal membrane oxygenation.

Interaction between native ventricular output and venoarterial extracorporeal membrane oxygenation (VA ECMO) flow may hinder oxygenated blood flow to the aortic arch branches, resulting in differential hypoxemia. Typically, the arterial cannula tip is placed in the iliac artery or abdominal aorta. However, the hemodynamics of a more proximal arterial cannula tip have not been studied before. This study investigated the effect of arterial cannula tip position on VA ECMO blood flow to the upper extremities using computational fluid dynamics simulations. Four arterial cannula tip positions (P1. common iliac, P2. abdominal aorta, P3. descending aorta and P4. aortic arch) were compared with different degrees of cardiac dysfunction and VA ECMO support (50%, 80% and 90% support). P4 was able to supply oxygenated blood to the arch vessels at all support levels, while P1 to P3 only supplied the arch vessels during the highest level (90%) of VA ECMO support. Even during the highest level of support, P1 to P3 could only provide oxygenated VA-ECMO flow at 0.11 L/min to the brachiocephalic artery, compared with 0.5 L/min at P4. This study suggests that cerebral perfusion of VA ECMO flow can be increased by advancing the arterial cannula tip towards the aortic arch.

Ex vivo evaluation of personal protective equipment in hands-on defibrillation.

Background: Defibrillation guidelines recommend avoiding patient contact during shock delivery. However, hands-on defibrillation (compressions during shock) and manual pressure augmentation (MPA - pushing on the defibrillator pads during shock) may lead to improved clinical outcomes. There are limited data addressing the protection provided by personal protective equipment (PPE) during hands-on defibrillation and MPA. This study investigated the hand-to-hand and hand-to-knee leakage current experienced by a simulated kneeling provider wearing different PPE. Methods: A defibrillator was used in experiments on a pork shoulder, investigating three different hands-on positions: closed fist on defibrillator pads; open palm on pads with inadvertent finger contact (overhang); and open palm on the chest. Evaluated PPE included single and double gloves (nitrile and latex) and rescuer cargo trousers in wet and dry conditions (N = 126 experiments). Results: Mean hand-to-hand leakage currents in MPA without PPE was 0.41 mA (0.2-0.74 mA) and with PPE was 0.2 mA (0.08-0.58 mA). For experiments involving finger or palm contact on the chest, wearing any PPE resulted in a >99% reduction in mean leakage currents from an average 354.58 mA (258.96-446.22 mA) to an average 0.48 mA (0.16-1.56 mA). Rescuer trousers were insulative in dry conditions even without gloves (0.2-1.2 mA). Conclusion: This study demonstrated that the tested clinical examination gloves markedly reduced leakage current to the rescuer and that the lowest levels of leakage current occurred during MPA attributed to the electrical insulation of the pads.

Hemodynamics of small arterial return cannulae for venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) provides mechanical support for critically ill patients with cardiogenic shock. Typically, the size of the arterial return cannula is chosen to maximize flow. However, smaller arterial cannulae may reduce cannula-related complications and be easier to insert. This in vitro study quantified the hemodynamic effect of different arterial return cannula sizes in a simulated acute heart failure patient. METHODS: Baseline support levels were simulated with a 17 Fr arterial cannula in an ECMO circuit attached to a cardiovascular simulator with targeted partial (2.0 L/min ECMO flow, 60-65 mm Hg mean aortic pressure-MAP) and targeted full ECMO support (3.5 L/min ECMO flow and 70-75 mm Hg MAP). Return cannula size was varied (13-21 Fr), and hemodynamics were recorded while keeping ECMO pump speed constant and adjusting pump speed to restore desired support levels. RESULTS: Minimal differences in hemodynamics were found between cannula sizes in partial support mode. A maximum pump speed change of +600 rpm was required to reach the support target, and arterial cannula inlet pressure varied from 79 (21 Fr) to 224 mm Hg (13 Fr). The 15 Fr arterial cannula could provide the target full ECMO support at the targeted hemodynamics; however, the 13 Fr cannula could not due to the high resistance associated with the small diameter. CONCLUSIONS: A 15 Fr arterial return cannula provided targeted partial and full ECMO support to a simulated acute heart failure patient. Balancing reduced cannula size and ECMO support level may improve patient outcomes by reducing cannula-related adverse events.

Intra-aortic Balloon Pump Use With Extra Corporeal Membrane Oxygenation-A Mock Circulation Loop Study.

Venoarterial extracorporeal membrane oxygenation (ECMO) is used in cardiogenic shock refractory to inotropic support and intra-aortic balloon pump (IABP) support. Peripheral ECMO can lead to ventricular distention, and IABP can be used to mitigate these effects. The aim of this study was to quantify the effects of IABP concomitant with ECMO, under different simulated hemodynamic conditions in a mock circulatory loop. Different simulated states of isolated left ventricular (LV) failure and biventricular failure with graded LV failure severities were supported with ECMO and ECMO with IABP. The impact on left ventricular end-diastolic pressure (LVEDP), volume (LVEDV), coronary flow rate, and cerebral flow rate were evaluated. Left ventricular volumes and pressures increased from the heart failure states with the addition of ECMO. The IABP provided between 3% and 7% reductions in LVEDP and between 1% and 10% reductions in LVEDV. The addition of IABP had minimal effect on cerebral blood flow (0% to 7%), but the variable impact on coronary blood flow with increased diastolic coronary flow of 23% to 50%, but the reduction in mean coronary flow by up to 30%. The efficacy of the IABP was strongly related to ventricular contractility. This study demonstrates the need for careful IABP selection concomitant with ECMO.

HeartWare HVAD Flow Estimator Accuracy for Left and Right Ventricular Support.

This study investigated the accuracy of the HeartWare HVAD flow estimator for left ventricular assist device (LVAD) support and biventricular assist device (BiVAD) support for modes of reduced speed (BiVAD-RS) and banded outflow (BiVAD-B). The HVAD flow estimator was evaluated in a mock circulatory loop under changes in systemic and pulmonary vascular resistance, heart rate, central venous pressure, and simulated hematocrit (correlated to viscosity). A difference was found between mean estimated and mean measured flow for LVAD (0.1 ± 0.3 L/min), BiVAD-RS (-0.1 ± 0.2 L/min), and BiVAD-B (0 ± 0.2 L/min). Analysis of the flow waveform pulsatility showed good correlation for LVAD (r2 = 0.98) with a modest spread in error (0.7 ± 0.1 L/min), while BiVAD-RS and BiVAD-B showed similar spread in error (0.7 ± 0.3 and 0.7 ± 0.2 L/min, respectively), with much lower correlation (r2 = 0.85 and r2 = 0.60, respectively). This study demonstrated that the mean flow error of the HVAD flow estimator is similar when the device is used in LVAD, BiVAD-RS, or BiVAD-B configuration. However, the instantaneous flow waveform should be interpreted with caution, particularly in the cases of BiVAD support.

Comparison of Circulatory Unloading Techniques for Venoarterial Extracorporeal Membrane Oxygenation.

Left ventricular (LV) distention and pulmonary congestion are major complications inherent to venoarterial extracorporeal membrane oxygenation (ECMO). This study aimed to quantitatively compare the hemodynamic differences between common circulatory unloading methods for ECMO. Ten circulatory unloading techniques were evaluated on a mock circulatory loop simulating acute LV failure supported by ECMO. Simulated unloading techniques included: surgical and percutaneous pulmonary artery (PA) venting, surgical left atrial venting, surgical and percutaneous LV venting, atrial septal defect, partial support ventricular assist device, intraaortic balloon pump, and temporary VAD with inline oxygenator (tVAD). The most LV unloading occurred with the surgically placed LV vent and tVAD, which reduced LV end-diastolic volume from 295 to 167 ml and 82 ml, respectively. Meanwhile, the PA surgical vent was the most effective at reducing mean PA pressure from 21.0 to 10.6 mm Hg, and the tVAD was most effective at reducing left atrial pressure from 13.3 to 4.4 mm Hg. The major limitation of this study was the use of a mock circulatory loop, which simulated lower left atrial pressure than is typically seen clinically. This study identified clinically significant hemodynamic variability between the different circulatory unloading techniques evaluated. However, the applicability of these techniques will vary with different patient disease etiology. Further studies on ECMO unloading will help to quantify hemodynamic benefits and establish treatment guidelines.

Physiological principles of Starling-like control of rotary ventricular assist devices.

Introduction: This review explores the Starling-like physiological control method (SLC) for rotary ventricular assist devices (VADs) for severe heart failure. The SLC, based on mathematical models of the circulation, has two functions modeling each ventricle. The first function controls the output of the VAD to the arterial pool according to Starling's law, while the second function accounts for how the blood returns to the heart from the veins. The article aims to expose clinicians to SLC in an accessible and clinically relevant discussion. Areas Covered: The article explores the physiology underlying the controller, its development and how that physiology can be adapted to SLC. Examples of controller performance are demonstrated and discussed using a benchtop model of the cardiovascular system. A discussion of the limitations and criticisms of SLC is presented, followed by a future outlook on the clinical adoption of SLC. Expert Opinion: Due to its simplicity and emulation of the natural cardiac autoregulation, SLC is the superior physiological control method for rotary VADs. However, current technical and regulatory challenges prevent the clinical translation of SLC of VADs. Further technical and regulatory development will enable the clinical translation of SLCs of VADs in the coming years.

The Importance of Venous Return in Starling-Like Control of Rotary Ventricular Assist Devices.

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling-like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC-P) against an SLC with a vertical VRL (SLC-V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC-P produced no overshoot or oscillations following step changes in preload, whereas SLC-V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC-V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( x ¯ = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( x ¯ = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.

Temperature Compensated Fibre Bragg Grating Pressure Sensor for Ventricular Assist Devices.

Rotary blood pumps may be used as ventricular assist devices (VADs) to support patients with end-stage heart failure-'rotary VADs'. Clinically, rotary VADs are operated at a constant speed which is set manually. Due to inadequate haemodynamic monitoring equipment outside of the hospital setting, device speed remains the same for weeks or months at a time, leaving clinicians in the dark, and patients vulnerable to harmful over- or under-pumping events. Therefore, it would be beneficial to have an implantable sensor which can measure blood pressure at the rotary VAD inlet or outlet and detect the onset of adverse events. In this study, a temperature compensated fibre Bragg grating (FBG) based strain sensor which can be incorporated into a VAD and used for continuous, real-time blood pressure monitoring is investigated. Error in the pressure reading between the developed and reference sensor occurred due to changes in temperature. A generalised linear model was used to compensate for temperature related error between 35-39º. Without temperature compensation, the mean error in the pressure reading over the desired range of -25 to 150 mmHg was approximately ±5 mmHg. The temperature compensated mean error over the same range was less than ±2 mmHg. The compensation technique was effective over a wide range of temperatures and pressures, demonstrating the potential of the sensor for continuous real-time blood pressure monitoring.

In Vitro Evaluation of an Immediate Response Starling-Like Controller for Dual Rotary Blood Pumps.

Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow-balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling-like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation. The comparison between CSC and SLC of dual HeartWare HVADs using a mock circulation loop to simulate biventricular heart failure has been reported. Four changes in cardiovascular state were simulated to test the controller, including a 700 mL reduction in circulating fluid volume, a total loss of left and right ventricular contractility, reduction in systemic vascular resistance ( SVR) from 1300 to 600 dyne  s/cm5, and an elevation in pulmonary vascular resistance ( PVR) from 100 to 300 dyne  s/cm5. SLC maintained the left and right ventricular volumes between 69-214 mL and 29-182 mL, respectively, for all tests, preventing ventricular suction (ventricular volume = 0 mL) and venous congestion (atrial pressures > 20 mm Hg). Cardiac output was maintained at sufficient levels by the SLC, with systemic and pulmonary flow rates maintained above 3.14 L/min for all tests. With the CSC, left ventricular suction occurred during reductions in SVR, elevations in PVR, and reduction in circulating fluid simulations. These results demonstrate a need for a physiological control system and provide adequate in vitro validation of the immediate response of a SLC for biventricular support.