Validation of the slaughterhouse porcine heart model for ex-situ heart perfusion studies.

INTRODUCTION: To validate slaughterhouse hearts for ex-situ heart perfusion studies, we compared cold oxygenated machine perfusion in less expensive porcine slaughterhouse hearts (N = 7) to porcine hearts that are harvested following the golden standard in laboratory animals (N = 6). METHODS: All hearts received modified St Thomas 2 crystalloid cardioplegia prior to 4 hours of cold oxygenated machine perfusion. Hearts were perfused with homemade modified Steen heart solution with a perfusion pressure of 20-25 mmHg to achieve a coronary flow between 100-200 mL/min. Reperfusion and testing was performed for 4 hours on a normothermic, oxygenated diluted whole blood loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mmHg. RESULTS: Both groups showed 100% functional survival, with laboratory hearts displaying superior cardiac function. Both groups showed similar decline in function over time. CONCLUSION: We conclude that the slaughterhouse heart can be used as an alternative to laboratory hearts and provides a cost-effective method for future ex-situ heart perfusion studies.

Investigating the physiology of normothermic ex vivo heart perfusion in an isolated slaughterhouse porcine model used for device testing and training.

BACKGROUND: The PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and able to validate cardiac devices and techniques in working mode. Despite perfusion, myocardial edema and time-dependent function degradation are reported. Therefore, monitoring several variables is necessary to identify which of these should be controlled to preserve the heart function. This study presents biochemical, electrophysiological and hemodynamic changes in the PhysioHeart™ to understand the pitfalls of ex vivo slaughterhouse heart hemoperfusion. METHODS: Seven porcine hearts were harvested, arrested and revived using the PhysioHeart™. Cardiac output, SaO2, glucose and pH were maintained at physiological levels. Blood analyses were performed hourly and unipolar epicardial electrograms (UEG), pressures and flows were recorded to assess the physiological performance. RESULTS: Normal cardiac performance was attained in terms of mean cardiac output (5.1 ± 1.7 l/min) and pressures but deteriorated over time. Across the experiments, homeostasis was maintained for 171.4 ± 54 min, osmolarity and blood electrolytes increased significantly between 10 and 80%, heart weight increased by 144 ± 41 g, free fatty acids (- 60%), glucose and lactate diminished, ammonia increased by 273 ± 76% and myocardial necrosis and UEG alterations appeared and aggravated. Progressively deteriorating electrophysiological and hemodynamic functions can be explained by reperfusion injury, waste product intoxication (i.e. hyperammonemia), lack of essential nutrients, ion imbalances and cardiac necrosis as a consequence of hepatological and nephrological plasma clearance absence. CONCLUSIONS: The PhysioHeart™ is an acute model, suitable for cardiac device and therapy assessment, which can precede conventional animal studies. However, observations indicate that ex vivo slaughterhouse hearts resemble cardiac physiology of deteriorating hearts in a multi-organ failure situation and signalize the need for plasma clearance during perfusion to attenuate time-dependent function degradation. The presented study therefore provides an in-dept understanding of the sources and reasons causing the cardiac function loss, as a first step for future effort to prolong cardiac perfusion in the PhysioHeart™. These findings could be also of potential interest for other cardiac platforms.

Impact of Laser Power and Firing Angle on Coagulation Efficiency in Laser Treatment for Twin-Twin Transfusion Syndrome: An ex vivo Placenta Study.

OBJECTIVE: To assess the impact of laser power and firing angle on coagulation efficiency for closing placental anastomoses in the treatment of twin-twin transfusion syndrome. METHODS: We used an ex vivo blood-perfused human placenta model to compare time to complete coagulation using 30 vs. 50 W of neodymium-doped yttrium aluminum garnet laser power and using a firing angle of 90° vs. 45°. Placentas were perfused with pig blood at 5 mL/min. Differences were analyzed using independent-samples t test, Mann-Whitney U test, or χ2 test as appropriate. RESULTS: Coagulation took less time and energy using 50 W (n = 53) compared to 30 W (n = 52), 11 vs. 22 s (p < 0.001), and 557 vs. 659 J (p = 0.007). Perpendicular coagulation (n = 53) took less time and energy compared to a 45° angle (n = 21), 11 vs. 17 s (p = 0.004), and 557 vs. 871 J (p = 0.004). Bleeding complicated 2 (3%) measurements in the 50-W group, 5 (10%) in the 30-W group, and 3 (14%) in the 45° group. DISCUSSION: In a highly controlled model, a 50-W laser power setting was more energy efficient than 30 W in coagulating a placental vein. A more perpendicular laser firing angle resulted in more efficient coagulation. Furthermore, bleeding due to vessel wall disruption occurred more often with lower power and a more tangential approach.

Ex vivo proof-of-concept of end-to-end scaffold-enhanced laser-assisted vascular anastomosis of porcine arteries.

OBJECTIVE: The low welding strength of laser-assisted vascular anastomosis (LAVA) has hampered the clinical application of LAVA as an alternative to suture anastomosis. To improve welding strength, LAVA in combination with solder and polymeric scaffolds (ssLAVA) has been optimized in vitro. Currently, ssLAVA requires proof-of-concept in a physiologically representative ex vivo model before advancing to in vivo studies. This study therefore investigated the feasibility of ex vivo ssLAVA in medium-sized porcine arteries. METHODS: Scaffolds composed of poly(ε-caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) were impregnated with semisolid solder and placed over coapted aortic segments. ssLAVA was performed with a 670-nm diode laser. In the first substudy, the optimum number of laser spots was determined by bursting pressure analysis. The second substudy investigated the resilience of the welds in a Langendorf-type pulsatile pressure setup, monitoring the number of failed vessels. The type of failure (cohesive vs adhesive) was confirmed by electron microscopy, and thermal damage was assessed histologically. The third substudy compared breaking strength of aortic repairs made with PLGA and semisolid genipin solder (ssLAVR) to repairs made with BioGlue. RESULTS: ssLAVA with 11 lasing spots and PLGA scaffold yielded the highest bursting pressure (923 ± 56 mm Hg vs 703 ± 96 mm Hg with PCL ssLAVA; P = .0002) and exhibited the fewest failures (20% vs 70% for PCL ssLAVA; P = .0218). The two failed PLGA ssLAVA arteries leaked at 19 and 22 hours, whereas the seven failed PCL ssLAVA arteries burst between 12 and 23 hours. PLGA anastomoses broke adhesively, whereas PCL welds failed cohesively. Both modalities exhibited full-thickness thermal damage. Repairs with PLGA scaffold yielded higher breaking strength than BioGlue repairs (323 ± 28 N/cm(2) vs 25 ± 4 N/cm(2), respectively; P = .0003). CONCLUSIONS: PLGA ssLAVA yields greater anastomotic strength and fewer anastomotic failures than PCL ssLAVA. Aortic repairs with BioGlue were inferior to those produced with PLGA ssLAVR. The results demonstrate the feasibility of ssLAVA/R as an alternative method to suture anastomosis or tissue sealant. Further studies should focus on reducing thermal damage.

Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure.

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.

Hemofiltration Improves Blood Perfusate Conditions Leading to Improved Ex Situ Heart Perfusion.

The aim was to optimize the perfusate composition by including a hemofiltrator to the PhysioHeartplatform for ex situ heart perfusion of porcine slaughterhouse hearts. Fourteen hearts were harvested from Dutch Landrace pigs and slaughtered for human consumption. All hearts were preserved for 4 hours using static cold storage before reperfusion for 4 hours on the PhysioHeart platform. Seven hearts were assigned to the hemofiltration group, where a hemofiltrator was added to the perfusion circuit, while the control group did not receive hemofiltration. In the hemofiltration group, the perfusion fluid was filtrated for 1 hour with a flow of 1 L/hour before reperfusion. After mounting the heart, hemofiltration was maintained at 1 L/hour, and cardiac function and blood samples were analyzed at multiple time points. Preserved cardiac function was defined as a cardiac output >3.0 L/min with a mean aortic pressure >60 mm Hg and a left atrial pressure <15 mm Hg. Hemofiltration resulted in a significantly reduced potassium concentration at all time points ( p < 0.001), while sodium levels remained at baseline values ( p < 0.004). Furthermore, creatinine and ammonia levels decreased over time. Functional assessment demonstrated a reduced left atrial pressure ( p < 0.04) and a reduction of the required dobutamine dose to support myocardial function ( p < 0.003) in the hemofiltration group. Preserved cardiac function did not differ between groups. Hemofiltration results in an improved biochemical composition of the whole blood perfusate and preserves cardiac function better during normothermic perfusion based on a reduced left atrial pressure (LAP) and dobutamine requirement to support function.

Autoregulation of coronary blood flow in the isolated beating pig heart.

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step-wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473 ± 40 g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well-controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments.

The evolution of technical prerequisites and local boundary conditions for optimization of mitral valve interventions-Emphasis on skills development and institutional risk performance.

This viewpoint report describes how the evolution of transcatheter mitral valve intervention (TMVI) is influenced by lessons learned from three evolutionary tracks: (1) the development of treatment from mitral valve surgery (MVS) to transcutaneous procedures; (2) the evolution of biomedical engineering for research and development resulting in predictable and safe clinical use; (3) the adaptation to local conditions, impact of transcatheter aortic valve replacement (TAVR) experience and creation of infrastructure for skills development and risk management. Thanks to developments in computer science and biostatistics, an increasing number of reports regarding clinical safety and effectiveness is generated. A full toolbox of techniques, devices and support technology is now available, especially in surgery. There is no doubt that the injury associated with a minimally invasive access reduces perioperative risks, but it may affect the effectiveness of the treatment due to incomplete correction. Based on literature, solutions and performance standards are formulated with an emphasis in technology and positive outcome. Despite references to Heart Team decision making, boundary conditions such as hospital infrastructure, caseload, skills training and perioperative risk management remain underexposed. The role of Biomedical Engineering is exclusively defined by the Research and Development (R&D) cycle including the impact of human factor engineering (HFE). Feasibility studies generate estimations of strengths and safety limitations. Usability testing reveals user friendliness and safety margins of clinical use. Apart from a certification requirement, this information should have an impact on the definition of necessary skills levels and consequent required training. Physicians Preference Testing (PPT) and use of a biosimulator are recommended. The example of the interaction between two Amsterdam heart centers describes the evolution of a professional ecosystem that can facilitate innovation. Adaptation to local conditions in terms of infrastructure, referrals and reimbursement, appears essential for the evolution of a complete mitral valve disease management program. Efficacy of institutional risk management performance (IRMP) and sufficient team skills should be embedded in an appropriate infrastructure that enables scale and offers complete and safe solutions for mitral valve disease. The longstanding evolution of mitral valve therapies is the result of working devices embedded in an ecosystem focused on developing skills and effective risk management actions.

MarioHeart: Novel In-Vitro Flow Model for Testing Heart Valve Prostheses and Anticoagulant Therapies.

Mechanical heart valve (MHV) prostheses present a risk of thromboembolic complications despite antithrombotic therapy. Further steps in the development of more hemocompatible MHVs and new anticoagulants are impeded due to the lack of adequate in-vitro models. With the development of a novel in-vitro model (MarioHeart), a pulsatile flow similar to the arterial circulation is emulated. The MarioHeart design owns unique features as 1) a single MHV within a torus with low surface/volume ratio, 2) a closed loop system, and 3) a dedicated external control system driving the oscillating rotational motion of the torus. For verification purposes, a blood analog fluid seeded with particles was used to assess fluid velocity and flow rate using a speckle tracking method on high-speed video recordings of the rotating model. The flow rate resembled the physiological flow rate in the aortic root, in both shape and amplitude. Additional in-vitro runs with porcine blood showed thrombi on the MHV associated with the suture ring, which is similar to the in-vivo situation. MarioHeart is a simple design which induces well-defined fluid dynamics resulting in physiologically nonturbulent flow without stasis of the blood. MarioHeart seems suitable for testing the thrombogenicity of MHVs and the potential of new anticoagulants.

Cold Oxygenated Machine Perfusion Improves Functional Survival of Slaughterhouse Porcine Hearts.

The aim of our study was to explore the effect of cold oxygenated machine perfusion in slaughterhouse porcine hearts on functional myocardial survival compared to static cold storage (SCS). Seventeen hearts were harvested from Dutch Landrace Hybrid pigs, which were sacrificed for human consumption and randomly assigned to the 4 hours SCS group (N = 10) or the 4 hours cold oxygenated machine perfusion group (N = 7). Hearts were perfused with a homemade Heart Solution with a perfusion pressure of 20-25 mm Hg to achieve a coronary flow between 100 and 200 ml/minute. After 4 hours of preservation, all hearts were functionally assessed during 4 hours on a normothermic, oxygenated diluted whole blood (1:2) loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mm Hg. Survival was significantly better in the cold oxygenated machine perfusion group, where 100% of the hearts reached the 4 hours end-point, as compared with 30% in the SCS group ( p = 0.006). Interestingly, warm ischemic time was inversely related to survival in the SCS group with a correlation coefficient of -0.754 ( p = 0.012). Cold oxygenated machine perfusion improves survival of the slaughterhouse porcine heart.

At the Crossroads of Minimally Invasive Mitral Valve Surgery-Benching Single Hospital Experience to a National Registry: A Plea for Risk Management Technology.

Almost 30 years after the first endoscopic mitral valve repair, Minimally Invasive Mitral Valve Surgery (MIMVS) has become the standard at many institutions due to optimal clinical results and fast recovery. The question that arises is can already good results be further improved by an Institutional Risk Management Performance (IRMP) system in decreasing risks in minimally invasive mitral valve surgery (MIMVS)? As of yet, there are no reports on IRMP and learning systems in the literature. (2) Methods: We described and appraised our five-year single institutional experience with MIMVS in isolated valve surgery included in the Netherlands Heart Registry (NHR) and investigated root causes of high-impact complications. (3) Results: The 120-day and 12-month mortality were 1.1% and 1.9%, respectively, compared to the average of 4.3% and 5.3% reported in the NHR. The regurgitation rate was 1.4% compared to 5.2% nationwide. The few high-impact complications appeared not to be preventable. (4) Discussion: In MIMVS, freedom from major and minor complications is a strong indicator of an effective IRMP but remains concealed from physicians and patients, despite its relevance to shared decision making. Innovation adds to the complexity of MIMVS and challenges surgical competence. An IRMP system may detect and control new risks earlier. (5) Conclusion: An IRMP system contributes to an effective reduction of risks, pain and discomfort; provides relevant input for shared decision making; and warrants the safe introduction of new technology. Crossroads conclusions: investment in machine learning and AI for an effective IRMP system is recommended and the roles for commanding and operating surgeons should be considered.

Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts.

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.

Attenuated cardiac function degradation in ex vivo pig hearts.

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, -14.9 ± 6.3%/h vs -9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, -11.8 ± 3.4%/h vs -5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

Low CT temporal sampling rates result in a substantial underestimation of myocardial blood flow measurements.

The purpose of this study was to evaluate the effect of temporal sampling rate in dynamic CT myocardial perfusion imaging (CTMPI) on myocardial blood flow (MBF). Dynamic perfusion CT underestimates myocardial blood flow compared to PET and SPECT values. For accurate quantitative analysis of myocardial perfusion with dynamic perfusion CT a stable calibrated HU measurement of MBF is essential. Three porcine hearts were perfused using an ex-vivo Langendorff model. Hemodynamic parameters were monitored. Dynamic CTMPI was performed using third generation dual source CT at 70 kVp and 230-350 mAs/rot in electrocardiography(ECG)-triggered shuttle-mode (sampling rate, 1 acquisition every 2-3 s; z-range, 10.2 cm), ECG-triggered non-shuttle mode (fixed table position) with stationary tube rotation (1 acquisition every 0.5-1 s, 5.8 cm), and non-ECG-triggered continuous mode (1 acquisition every 0.06 s, 5.8 cm). Stenosis was created in the circumflex artery, inducing different fractional flow reserve values. Volume perfusion CT Myocardium software was used to analyze ECG-triggered scans. For the non-ECG triggered scans MASS research version was used combined with an in-house Matlab script. MBF (mL/g/min) was calculated for non-ischemic segments. True MBF was calculated using input flow and heart weight. Significant differences in MBF between shuttle, non-shuttle and continuous mode were found, with median MBF of 0.87 [interquartile range 0.72-1.00], 1.20 (1.07-1.30) and 1.65 (1.40-1.88), respectively. The median MBF in shuttle mode was 56% lower than the true MBF. In non-shuttle and continuous mode, the underestimation was 41% and 18%. Limited temporal sampling rate in standard dynamic CTMPI techniques contributes to substantial underestimation of true MBF.

Feasibility of mapping and cannulation of the porcine epicardial lymphatic system for sampling and decompression in heart failure research.

BACKGROUND AND AIM: The cardiac lymphatic system drains excess fluid from the cardiac interstitium. Any impairment or dysfunction of the lymph structures can result in the accumulation of interstitial fluid, and may lead to edema and eventually cardiac dysfunction. Lymph originates directly from the interstitium and carries real-time information about the metabolic state of cells in specific regions of the heart. The detailed anatomy of the epicardial lymphatic system in individuals is broadly unknown. Generally, the epicardial lymphatic system is not taken into consideration during heart surgery. This study investigates the feasibility of detailed mapping and cannulation of the porcine epicardial lymphatic system for use in preservation of explanted hearts and heart failure studies in pigs and humans. METHODS: The anatomy of the epicardial lymphatic systems of forty pig hearts was studied and documented. Using a 27 G needle, India ink was introduced directly into the epicardial lymphatic vessels in order to visualise them. Based on the anatomical findings thus obtained, two cannulation regions for the left and right principal trunks were identified. These regions were cannulated with a 26 G intravenous Venflon cannula-over-needle, and a Galeo Hydro Guide F014 wire was used to verify that the lumen was patent. RESULTS: The main epicardial lymphatic collectors were found to follow the main coronary arteries. Most of the lymph vessels drained into the left ventricular trunk, which evacuates fluid from the left heart and also partially from the right heart. The right trunk was often found to drain into the left trunk anterior basally. Right heart drainage was highly variable compared to the left. In addition, the overall cannulation success rate of the selected cannulation sites was only 57%. CONSLUSIONS: Mapping of the porcine epicardial lymphatic anatomy is feasible. The right ventricular drainage system had a higher degree of variability than the left, and the right cardiac lymph system was found to be partially cleared through the left lymphatic trunk. To improve cannulation success rate, we proposed two sites for cannulation based on these findings and the use of Venflon cannulas (26 G) for cannulation and lymph collection. This method might be helpful for future studies that focus on biochemical sample analysis and decompression. RELEVANCE FOR PATIENTS: Real-time biochemical assessment and decompression of lymph may contribute to the understanding of heart failure and eventually result in preventive measures. First its relevance should be established by additional research in both arrested and working porcine hearts. Imaging and mapping of the epicardial lymphatics may enable sampling and drainage and contribute to the prevention or treatment of heart failure. We envision that this approach may be considered in patients with a high risk of postoperative left and right heart failure during open-heart surgery.

Full-field analysis of epicardial strain in an in vitro porcine heart platform.

The quantitative assessment of cardiac strain is increasingly performed to provide valuable insights on heart function. Currently, the most frequently used technique in the clinic is ultrasound-based speckle tracking echocardiography (STE). However, verification and validation of this modality are still under investigation and further reference measurements are required to support this activity. The aim of this work was to enable these reference measurements using a dynamic beating heart simulator to ensure reproducible, controlled, and realistic haemodynamic conditions and to validate the reliability of optical-based three-dimensional digital image correlation (3D-DIC) for a dynamic full-field analysis of epicardial strain. Specifically, performance assessment of 3D-DIC was carried out by evaluating the accuracy and repeatability of the strain measurements across multiple cardiac cycles in a single heart and between five hearts. Moreover, the ability of this optical method to differentiate strain variations when different haemodynamic conditions were imposed in the same heart was examined. Strain measurements were successfully accomplished in a region of the lateral left ventricle surface. Results were highly repeatable over heartbeats and across hearts (intraclass correlation coefficient = 0.99), whilst strain magnitude was significantly different between hearts, due to change in anatomy and wall thickness. Within an individual heart, strain variations between different haemodynamic scenarios were greater than the estimated error of the measurement technique. This study demonstrated the feasibility of applying 3D-DIC in a dynamic passive heart simulator. Most importantly, non-contact measurements were obtained at a high spatial resolution (~ 1.5 mm) allowing resolution of local variation of strain on the epicardial surface during ventricular filling. The experimental framework developed in this paper provides detailed measurement of cardiac strains under controlled conditions, as a reference for validation of clinical cardiac strain imaging modalities.

Ex Vivo Pilot Study of Cardiac Magnetic Resonance Velocity Mapping for Quantification of Aortic Regurgitation in a Porcine Model in the Presence of a Transcatheter Heart Valve.

Accuracy of aortic regurgitation (AR) quantification by magnetic resonance (MR) imaging in the presence of a transcatheter heart valve (THV) remains to be established. We evaluated the accuracy of cardiac MR velocity mapping for quantification of antegrade flow (AF) and retrograde flow (RF) across a THV and the optimal slice position to use in cardiac MR imaging. In a systematic and fully controlled laboratory ex vivo setting, two THVs (Edwards SAPIEN XT, Medtronic CoreValve) were tested in a porcine model (n = 1) under steady flow conditions. Results showed a high level of accuracy and precision. For both THVs, AF was best measured at left ventricular outflow tract level, and RF at ascending aorta level. At these levels, MR had an excellent repeatability (ICC > 0.99), with a tendency to overestimate (4.6 ± 2.4% to 9.4 ± 7.0%). Quantification of AR by MR velocity mapping in the presence of a THV was accurate, precise, and repeatable in this pilot study, when corrected for the systematic error and when the best MR slice position was used. Confirmation of these results in future clinical studies would be a step forward in increasing the accuracy of the assessment of paravalvular AR severity.

An isolated beating pig heart platform for a comprehensive evaluation of intracardiac blood flow with 4D flow MRI: a feasibility study.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) in large animals is cumbersome for various reasons, including ethical considerations, costs of housing and maintenance, and need for anaesthesia. Our primary purpose was to show the feasibility of an isolated beating pig heart model for four-dimensional (4D) flow MRI for investigating intracardiac blood flow patterns and flow parameters using slaughterhouse side products. In addition, the feasibility of evaluating transcatheter aortic valve replacement (TAVR) in the model was investigated. METHODS: Seven slaughterhouse pig hearts were installed in the MRI-compatible isolated beating pig heart platform. First, Langendorff perfusion mode was established; then, the system switched to working mode, in which blood was actively pumped by the left ventricle. A pacemaker ensured a stable HR during 3-T MRI scanning. All hearts were submitted to human physiological conditions of cardiac output and stayed vital for several hours. Aortic flow was measured from which stroke volume, cardiac output, and regurgitation fraction were calculated. RESULTS: 4D flow MRI acquisitions were successfully conducted in all hearts. Stroke volume was 31 ± 6 mL (mean ± standard deviation), cardiac output 3.3 ± 0.9 L/min, and regurgitation fraction 16% ± 9%. With 4D flow, intracardiac and coronary flow patterns could be visualised in all hearts. In addition, we could study valve function and regurgitation in two hearts after TAVR. CONCLUSIONS: The feasibility of 4D flow MRI in an isolated beating pig heart loaded to physiological conditions was demonstrated. The platform is promising for preclinical assessment of cardiac blood flow and function.

The dynamic cardiac biosimulator: A method for training physicians in beating-heart mitral valve repair procedures.

OBJECTIVE: Previously, cardiac surgeons and cardiologists learned to operate new clinical devices for the first time in the operating room or catheterization laboratory. We describe a biosimulator that recapitulates normal heart valve physiology with associated real-time hemodynamic performance. METHODS: To highlight the advantages of this simulation platform, transventricular extruded polytetrafluoroethylene artificial chordae were attached to repair flail or prolapsing mitral valve leaflets. Guidance for key repair steps was by 2-dimensional/3-dimensional echocardiography and simultaneous intracardiac videoscopy. RESULTS: Multiple surgeons have assessed the use of this biosimulator during artificial chordae implantations. This simulation platform recapitulates normal and pathologic mitral valve function with associated hemodynamic changes. Clinical situations were replicated in the simulator and echocardiography was used for navigation, followed by videoscopic confirmation. CONCLUSIONS: This beating heart biosimulator reproduces prolapsing mitral leaflet pathology. It may be the ideal platform for surgeon and cardiologist training on many transcatheter and beating heart procedures.

Beating heart porcine high-fidelity simulator for the training of edge-to-edge mitral valve repair.

Transcatheter treatment of structural heart disease is becoming an everyday reality for an increasing number of surgeons, and effective training modalities for basic guide-wire skills, catheter handling, and periprocedural imaging are of growing relevance. In this video tutorial we present a beating-heart porcine model used as a high-fidelity training simulator for transcatheter cardiac valve procedures.  We demonstrate a complete transcatheter edge-to-edge mitral valve repair procedure, including periprocedural imaging, clip deployment, and quality control. Various mitral valve pathologies can be simulated, including the demonstrated leaflet prolapse. Trainees practice clip navigation within the left atrium, transmitral passage, and clip orientation as well as grasping mitral valve leaflets to treat mitral regurgitation.  Periprocedural imaging is achieved via epicardial echocardiography and left ventricular cardioscopy, and these imaging modalities are also relied on to guide surgeons during the simulations, as required. The beating heart model enables realistic demonstration of the hemodynamic consequences of valve repair, and we believe that this simulator represents a valuable adjunct to surgical training.