Animated simulations of cardiogenic shock, VA ECMO and unloading interventions, and related tutorials can be found in the Supplemental Videos 1–12 (see Video 1, Supplemental Digital Content, http://links.lww.com/ASAIO/A236; see Video 2, Supplemental Digital Content, http://links.lww.com/ASAIO/A237; see Video 3, Supplemental Digital Content, http://links.lww.com/ASAIO/A238; see Video 4, Supplemental Digital Content, http://links.lww.com/ASAIO/A239; see Video 5, Supplemental Digital Content, http://links.lww.com/ASAIO/A240; see Video 6, Supplemental Digital Content, http://links.lww.com/ASAIO/A241; see Video 7, Supplemental Digital Content, http://links.lww.com/ASAIO/A242; see Video 8, Supplemental Digital Content, http://links.lww.com/ASAIO/A243; see Video 9, Supplemental Digital Content, http://links.lww.com/ASAIO/A244; see Video 10, Supplemental Digital Content, http://links.lww.com/ASAIO/A245; see Video 11, Supplemental Digital Content, http://links.lww.com/ASAIO/A246; see Video 12, Supplemental Digital Content, http://links.lww.com/ASAIO/A247;).
Our simulation study demonstrates that LV filling pressures, cavity volumes, and myocardial oxygen consumption increase progressively with VA ECMO flow, as reported previously.2 The degree of LV loading and unloading during VA ECMO is largely dependent on the absolute VA ECMO flow, the intrinsic LV contractility, or recruitable contractile reserve. Next, it is significantly influenced by specific cardiac unloading measures applied in conjunction with VA ECMO, ranging from medical to percutaneous or surgical interventions.
Individualized Management of Cardiac Overload in VA ECMO
The bedside integration of hemodynamics, cardiac geometry, and function during VA ECMO is not straightforward. Computer simulation of cardiovascular dynamics using clinical data as input may help to monitor cardiac loading in relation to the degree of VA ECMO support over time.2 This approach awaits further clinical validation but has the potential to provide bedside decision support to tailor individualized LV unloading. To the best of our knowledge, the modeling results presented here are unique, as they allow instantaneous quantification of cardiac loading or unloading in a generic patient with severe left heart failure by simulating clinically relevant adjuncts to VA ECMO. Three aspects essentially dictate the degree of individually required LV unloading: avoiding a nonejecting LV, preventing pulmonary edema, and ultimately facilitating optimal LV unloading and myocardial recovery.
The simulations presented here support the relevance of optimal medical management, as fluid removal while minimizing VA ECMO flow, reducing blood pressure, and eventually adding inotropes will significantly reduce PCWP and prevent pulmonary edema (Figures 2–4 and Table 1 (Row 4–6). Interventions such as the combined approach of VA ECMO and IABP have long been clinically applied to augment pulsatility, decrease afterload, and improve blood flow in native coronary arteries and bypass grafts.10,11 In the simulation, this combined approach showed only limited LV unloading, although pulsatility and increased stroke volume were noted. Recent clinical data support this notion for different clinical settings and do not advocate a routine combination of VA ECMO and IABP.12 Clinical studies have shown a slight reduction in PCWP, LV dimensions, and pulmonary edema in line with our simulation.13,14
Patients showing PCWP above 25 mm Hg or a virtually nonejecting LV will require interventional or surgical adjunct measures, which theoretically reduce PCWP by more than 5 mm Hg (Figures 6–9 and Table 1 (Row 7–17)).
The Impella 2.5, the larger CP, and the 5.0 surgical device have been used in conjunction with VA ECMO and allow clinically relevant cardiac unloading by reduction of right atrial and PCWP, as well as left-sided volumes and pulmonary edema.15–18 Our results support the considerable LV unloading potential as a function of Impella flow (Figure 6 and Table 1 (Row 8–10)).
The creation of an atrial septal defect is another valid intervention in this setting, as the simulation reveals that LV unloading is immediate and substantial, which has also been verified clinically19; but sizing of the defect can be critical because too much unloading may result in a nonejecting LV (Figure 7 and Table 1 (Row 13–14)). A well-controlled size of the atrial septal defect can be created with a specially designed percutaneous device available in different sizes and allowing permanent closure after use.20,21 Likewise, LV venting via atrial trans-septal cannulation has been reported,22 while the hemodynamic effects of percutaneous venting using a cannula positioned in the left atrium are similar to an atrial septostomy, as simulated (Figures 7 and 8). Alternatively, percutaneous LV venting by a transaortic catheter via axillary23 or femoral artery access24 or using a transpulmonary artery catheter has been proposed in clinical reports.22 Direct LV venting via an apical access or a cannula vent in the right superior pulmonary vein usually requires sternotomy or thoracotomy.20,25 These surgical approaches generally allow larger cannulae, higher flows, and substantial LV unloading (Figures 8 and 9 and Table 1 (Row 15–17)), yet carry inherent surgical risks.
The choice for IABP, specific Impella, or direct or indirect percutaneous or surgical LV venting depends on the individual clinical setting. The risks of LV overload, pulmonary edema, and thrombus formation because of a nonejecting LV should be weighed against time expected for recovery and interventional risks. Our analysis demonstrates that every measure taken to adjust LV loading conditions can potentially be scrutinized in advance with an adequate patient-specific simulation. In this way, management of peripheral VA ECMO may potentially be optimized with a minimum of unwanted side effects.
Complex regulatory systems, for example, baroreceptor reflex and other autoregulatory adaptations to hemodynamic changes, have not been simulated to allow a pure analysis of cardiac unloading effects during VA ECMO support. It can be expected that the increase in total cardiac output caused by VA ECMO results in decreased sympathetic activity and may explain minor differences between simulation results and reported clinical and experimental data.2,4 Moreover, an increase in heart rate usually accompanying inotropics or enhanced neurohumoral tone cannot be seen in the LV PV loop of a single cardiac cycle, but may affect myocardial oxygen balance unfavorably. Next, although included in the model, mechanical ventilatory settings, related intrathoracic pressure variations, as well as pulmonary shunting and edema have not been simulated to allow an unbiased analysis of LV unloading.2 Furthermore, the model does not allow to simulate 3-dimensional blood flow patterns and changes in cardiac geometry, for example, in patients with ischemic heart failure and LV dyssynchrony. However, adding these features would make real-time simulation and interaction with loading conditions impossible when aiming to simulate in the context of a clinically realistic time frame. Similarly, treatment consequences related to hemolysis and coagulation disorders are clinically relevant, but beyond the scope of the current study, while the model allows for changes in hemoglobin/hematocrit, influencing the blood viscosity within a specific simulation.
Simulation results demonstrate that VA ECMO per se increases LV loading. The combined use of conservative measures may result in acceptable LV unloading in a majority of VA ECMO cases. Adjunct percutaneous or surgical interventions allow substantial LV unloading, which may be justified in well-selected patients. Cardiovascular simulation may in the future potentially be used clinically to improve prediction of hemodynamic and cardiac effects of these interventions to optimize VA ECMO support in individual patients.
M. Broomé constructed the model, performed programming, simulation runs and drafted the manuscript. D. W. Donker, D. Brodie, and J. P. S. Henriques drafted the manuscript. M. Broomé, D. W. Donker, D. Brodie and J. P. S. Henriques all participated in the evaluation of the clinical relevance of the model as being clinically active medical doctors taking care of ECMO patients. All authors read and approved the final manuscript.
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Veno-arterial extracorporeal membrane oxygenation; extracorporeal life support; cardiogenic shock; cardiovascular modeling; computer simulation
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