Design and Validation of a High-Fidelity Left Atrial Cardiac Simulator for the Study and Advancement of Left Atrial Appendage Occlusion

Figures

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  Fig. 1. Left atrial cardiac simulator for the study and advancement of left atrial appendage occlusion. (A) Location of the LAA within the heart and representation of thrombus formation during atrial fibrillation. AF is caused by abnormal electrical activity. Disordered electrical propagation causes disorganized stimulation of the myocardium and subsequent arrhythmic contractions. AF decreases contractility, resulting in blood stasis and diminished peak flow velocities. AF is also associated with endothelial damage, fibrosis, and inflammation, especially within the LAA, which leads to a prothrombotic and hypercoagulable state. This association is consistent with “Virchow’s Triad”, which synthesizes the pathogenesis of clot formation in the LAA in patients with AF: abnormal blood flow (stasis), endocardial dysfunction (vessel wall injury), and altered hemostasis (hypercoagulability). (B-C) Workflow from clinical imaging to rigid, patient-derived LA model. (B) Image segmentation, post-processing, and addition of model features for LAA attachment, septal crossing and integration with circulatory flow loop. (C) 3D printed rigid patient-derived model. LA: left atrium; LAA: left atrial…

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  Fig. 2. Schematic of circulatory flow loop and incorporation of patient-derived LA model to achieve LA cardiac simulator. (A) Schematic of circulatory flow loop with patient-derived LA model, pulsatile pump, commercially available mechanical heart valve in the mitral position, and tunable resistance and Windkessel-based compliance elements to mimic pulmonary and systemic vasculature. Instrumentation and corresponding measured values indicated (Q indicates flow; P indicates pressure). Total flow (QTot) is measured at the outflow of the pulsatile pump. Flow (Q) is measured at the four pulmonary vein inlets. Pressure (P) is measured at the four pulmonary vein inlets, the left atrium, the left atrial appendage, and the simulated left ventricle and aorta. (B) 3D rendering of LA model composed of patient-specific soft elastomeric LAA coupled to 3DP patient-derived rigid LA. The LA model has four inflows (RIPV, RSPV, LSPV, LIPV) and one outflow (MV). The model can be customized by varying the LA geometry (~ days) or interchanging the LAA geometry (~ minutes) from the library of LAA models of varying geometry and material properties. (C) Realization of LA model. Complete LA model with LAA1…

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  Fig. 3. Validation of LA cardiac simulator by demonstrating physiological and pathological hemodynamics. (A) Mean LAP achieved in LA cardiac simulator validated against reference data (Supplementary Table 2) from healthy adults (dotted green lines) and clinical data measured in patients with AF (n = 435), SEC (n = 32) and post-LAAO (n = 250). LAA1 (healthy patient) was used in the simulator to collect “Healthy” data. LAA4 (AF patient) was used in the simulator to collect “AF”, “SEC” and “Post-LAAO” data. The simulator was tuned by varying the pump heart rate, pump stroke volume, resistance, compliance and static reservoir height to achieve the target pressure values. Reference data for healthy adults from UpToDate (Supplementary Table 4). Clinical data from collaborators at Mayo Clinic (Supplementary Table 5). LAP: left atrial pressure; AF: atrial fibrillation; SEC: spontaneous echo contrast; post-LAAO: post-left atrial appendage occlusion. (B) Mean LA inflow achieved in LA cardiac simulator at varying pump stroke volume (45–90 mL) and pump heart rate (60–160 BPM). Data collected with LAA1. Red shading indicates range of mean LA inflows in patients with AF referenced from the literature…

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  Fig. 4. Hemodynamic changes following LAAO in LA cardiac simulator. (A) (i) LA model with acrylic cap sealed over ostium to simulate complete LAA exclusion or long-term occlusion following device endothelialization. (ii) LA model with 24 mm WATCHMAN FLX™ Left Atrial Appendage Closure Device (Boston Scientific) deployed in LAA2. (ii) LA model with no device in LAA2. (iv) LA pressure amplitude (LAPPulsePressure = LAPmaxima – LAPminima) before (No Device) and after LAAO with a 24 mm FLX (24 mm FLX) or a silicone coated impermeable 24 mm FLX device (Coated 24 mm FLX), or exclusion with an acrylic cap (Acrylic Cap). All data collected at 60 BPM and pump SV of 90 mL. Dunnett’s T3 multiple comparisons test, **** <0.0001, *** <0.0002, ** <0.0021, * <0.0332, ns = not significant. (v) Mean flow before (No Device) and after LAAO with a silicone-coated impermeable FLX device (Coated FLX). Inflow is defined as the sum of the mean flow through the four pulmonary veins. All data collected at 70 BPM and pump SV of 70 mL or 80 mL. (vi) Mean difference in volume per beat between inflow and outflow before (No Device) and after LAAO with a silicone coated impermeable FLX device (Coated FLX). All data…

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  Fig. 5. Evaluating LAAO in LA cardiac simulator. (A) Comparing occlusiveness of different devices in the cardiac simulator. (i) Following device deployment, a green dye was injected into the LAA distal to the device while color intensity was monitored in the LAA. The time to return to baseline color intensity in the LAA pre-injection was used as a surrogate for the degree of occlusiveness. Two 24 mm WATCHMAN FLX devices were deployed. The first device was a normal WATCHMAN FLX with a permeable polyethylene terephthalate (PET) fabric cover. The second device was a WATCHMAN FLX with an impermeable silicone coating on the PET fabric cover. (ii-iii) Dye was injected into the LAA and could be monitored visually for washout while pressure was measured continuously. (iii-iv, right) An endoscopic camera was used to visualize the LA portion of the device. (iv) Color intensity in the LAA following dye injection. Data are normalized from pre-injection baseline intensity to maximum intensity reached following dye injection. Time above baseline intensity indicated by shaded region. Time of dye injection indicated by vertical dashed line. (v) Time for color intensity in the LAA to decrease by 40% from…

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  Fig. 6. LAAO procedural training in LA cardiac simulator. (A) Repeated device deployment and recapture performed by an experienced user using the Access System and Delivery System in the cardiac simulator. (i) Schematic of LA model that allows septal crossing with a delivery sheath and device deployment into the LAA. (ii) LA model with delivery sheath advanced into the LAA. LAA model allows direct visualization for enhanced user-feedback. (iii-vi) Repeated device deployment and recapture until PASS™ (position, anchor, size, seal) criteria are met. Device release (vi, right) when user is satisfied with device deployment