Porcine Heart Research Articles

A Ring-Shaped MEMS-Based Piezoresistive Force Sensor for Cardiac Ablation Catheters

Catheter ablation, a minimally invasive surgical procedure that uses radiofrequency (RF), has simplified the treatment process of cardiac arrhythmias. The success of cardiac ablation procedures greatly depends on the effective lesion formation, which relies on the contact force between tissue and the tip. Thus, a real-time estimate of catheter tip contact force is essential during cardiac ablation procedures. We present the design, fabrication, and characterization of a piezoresistive Micro-Electro-Mechanical System (MEMS)-based force sensor for measuring catheter tip contact force in real-time. The sensor has four bridges with boron-doped piezoresistive elements for detecting the contact force. The sensor dimensions and the piezoresistors doping concentrations were optimized using finite element analysis. The sensor is designed to measure a catheter tip contact force between 0 – 0.8 N. An in-house indentation setup is developed and integrated with a commercial load cell to characterize the fabricated sensor. The sensor results showed a linearity of 99.5 %, maximum hysteresis of 5 %, and sensitivity of 108 ± <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$11 \Omega $ </tex-math></inline-formula> /N. A customized catheter tip integrated with the fabricated force sensor was tested on excised porcine heart tissues to measure the catheter tip contact force.

Cardiac mesh morphing method for finite element modeling of heart failure with preserved ejection fraction

Numerical modeling of heart biomechanics can realistically capture morphological variations in diseases and has been helpful in advancing our understanding of the physiology. Subject-specific models require anatomic representation of medical images, and it is desirable to have a consistently repeatable models for any given morphology. In this study, we propose a novel and easily adaptable cardiac reconstruction algorithm by morphing an existing discretized mesh of an advanced finite element (FE) model, to match anatomies acquired from porcine cardiac magnetic resonance imaging (cMRI) scans. The morphing algorithm involves iterative FE simulations with visco-hyperelastic material properties. The living heart porcine model (LHPM) was chosen as the input baseline FE mesh, in order to preserve detailed anatomical features that cannot be captured in routine scans such as myofiber orientations and conduction pathways. The algorithm was demonstrated for the recreation of porcine hearts of a healthy subject and of a subject induced with heart failure with preserved ejection fraction (HFpEF) conditions, where there were substantial hypertrophy and anatomical alterations. We further used the morphed meshes for FE modeling of cardiac contraction and relaxation, thus demonstrating the applicability of the proposed algorithm in producing viable meshes. The results show that our algorithm can recreate the characteristic anatomical changes of cardiac remodeling, including heart muscle thickening, as well as replicate the reduction in ventricular volume. This algorithm allows for the creation of subject-specific models with the same mesh connectivity, thus enabling spatial comparison and analysis of pathologic progress.

Detachment Force of the Helical Anchor in Mitral Annulus

Helical anchors are used in transcatheter mitral valve repair. The aim of the current study was to investigate effect of helical anchor design, anchored position and biting depth on the detachment force in an in-vitro experiment. Mitral annulus was excised from 36 fresh porcine hearts and mounted in an unaxial test rig. Seven helical anchors were made of stainless steel based on the geometric parameters: outer diameter, wire diameter, and pitch. The helical anchors were screwed in at 3 to 9 o'clock positions of the posterior annulus, namely, P3-9, and pulled out. The pullout force was measured with the maximal pullout force defined as the detachment force. The detachment force within the medial, lateral and central positions were comparable (p ​> ​=0.069). The detachment force at P6 was lowest compared with the medial and lateral positions, and was 5.459 ​± ​0.193 ​N, 5.586 ​± ​0.113 ​N, 8.911 ​± ​0.250 ​N for the anchors in the outer diameters of 3, 4, 5 ​mm, respectively at the pitch of 2 ​mm and the wire diameter of 0.4 ​mm and biting depth of 3 coils. The detachment force increased with the outer and wire diameters, but was not affected by the pitch at the biting depth of 3 coils (p ​≥ ​0.279). The detachment force of the helical anchor is lowest in the central posterior annulus region, and the biting depth in 3 or more coils is recommended. The helical anchor is stronger than the suture.

Extrapolation of Ventricular Activation Times From Sparse Electroanatomical Data Using Graph Convolutional Neural Networks.

Electroanatomic mapping is the gold standard for the assessment of ventricular tachycardia. Acquiring high resolution electroanatomic maps is technically challenging and may require interpolation methods to obtain dense measurements. These methods, however, cannot recover activation times in the entire biventricular domain. This work investigates the use of graph convolutional neural networks to estimate biventricular activation times from sparse measurements. Our method is trained on more than 15,000 synthetic examples of realistic ventricular depolarization patterns generated by a computational electrophysiology model. Using geometries sampled from a statistical shape model of biventricular anatomy, diverse wave dynamics are induced by randomly sampling scar and border zone distributions, locations of initial activation, and tissue conduction velocities. Once trained, the method accurately reconstructs biventricular activation times in left-out synthetic simulations with a mean absolute error of 3.9 ms ± 4.2 ms at a sampling density of one measurement sample per cm2. The total activation time is matched with a mean error of 1.4 ms ± 1.4 ms. A significant decrease in errors is observed in all heart zones with an increased number of samples. Without re-training, the network is further evaluated on two datasets: (1) an in-house dataset comprising four ischemic porcine hearts with dense endocardial activation maps; (2) the CRT-EPIGGY19 challenge data comprising endo- and epicardial measurements of 5 infarcted and 6 non-infarcted swines. In both setups the neural network recovers biventricular activation times with a mean absolute error of less than 10 ms even when providing only a subset of endocardial measurements as input. Furthermore, we present a simple approach to suggest new measurement locations in real-time based on the estimated uncertainty of the graph network predictions. The model-guided selection of measurement locations allows to reduce by 40% the number of measurements required in a random sampling strategy, while achieving the same prediction error. In all the tested scenarios, the proposed approach estimates biventricular activation times with comparable or better performance than a personalized computational model and significant runtime advantages.

Thrombin and factor Xa promote premature senescence and remodeling in areas at risk of the left appendage and in atrial endothelial cells: potential modulation by SGLT1 and/or SGLT2 inhibition

Abstract Introduction Atrial fibrillation (AF), the most common cardiac arrhythmia, promotes prothrombotic responses particularly in the distal part of the left atrial appendage (LAA) characterized by reduced flow and low shear stress. AF occurrence and duration are closely associated with endothelial dysfunction and left atrium remodeling. The contribution of coagulation factors thrombin and factor Xa (FXa) to LA remodeling remains poorly studied. This study investigated whether thrombin and FXa promote endothelial dysfunction and profibrotic and prothrombotic responses in the distal and proximal parts of the LAA. Since SGLT2 inhibitors have shown pronounced cardiac protection, the contribution of SGLT2 was examined. Methods LAAs were harvested from porcine hearts. Proximal (low stasis, high shear) and distal (high stasis, low shear) parts were cut and incubated with a coagulation factor (thrombin or FXa). Left atrial endothelial cells (AECs) were collected enzymatically, cultured and used at passage 1. The level of oxidative stress was assessed using the redox-sensitive probe dihydroethidium (DHE), fibrosis by Sirius red histological staining, senescence-associated β-galactosidase (SA-β-gal) activity using X-gal staining in tissues and the fluorogenic substrate C12FDG and flow cytometry in cells. The expression of target proteins was detected by immunofluorescence staining and Western blot analysis. Results The distal part of LAA displayed higher levels of oxidative stress in the endothelium and the atrial wall than the proximal part. SA-β-gal activity, ICAM-1, VCAM-1, and MMP-9 staining was more pronounced in the endothelium of the distal part compared to the proximal part whereas eNOS staining was decreased. The distal LAA wall showed higher levels of fibrosis. Western blot analysis showed higher expression levels of tissue factor (TF), VCAM-1, MCP-1, MMP-9, TGF-β and SGLT-2 in the distal part compared to the proximal one. Both thrombin and FXa increased these signals to a greater extent in the distal part of the LAA whereas the eNOS expression level was decreased. Exposure of AECs to either thrombin or FXa induced a pro-oxidant response and increased the expression level of ICAM-1, TGF-β, MMP-2, MMP-9, SGLT1 and SGLT-2. Thrombin promoted SA-β-gal activity in AECs. The selective SGLT-2 inhibitor empagliflozin and the dual SGLT1/2 inhibitor sotagliflozin prevented the pro-oxidant response and SA-β-gal activity in response to thrombin. Conclusion Thus, the distal part of the LAA is prematurely affected by endothelial dysfunction and senescence associated with a pro-oxidant, pro-remodeling and pro-inflammatory response that is further increased by thrombin and FXa. Hence, the coagulation cascade appears to prematurely promote atrial endothelium and wall dysfunction predominantly in areas at risk that may pave the way to thrombus formation. The findings also suggest a potential protective effect of SGLT1 and/or SGLT2 inhibition on atrial dysfunction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted research grant from Boehringer Ingelheim Pharma GmbH &amp; Co. KG, Biberach, Germany

Insulin-Degrading Enzyme Regulates the Proliferation and Apoptosis of Porcine Skeletal Muscle Stem Cells via Myostatin/MYOD Pathway.

Identifying the genes relevant for muscle development is pivotal to improve meat production and quality in pigs. Insulin-degrading enzyme (IDE), a thiol zinc-metalloendopeptidase, has been known to regulate the myogenic process of mouse and rat myoblast cell lines, while its myogenic role in pigs remained elusive. Therefore, the current study aimed to identify the effects of IDE on the proliferation and apoptosis of porcine skeletal muscle stem cells (PSMSCs) and underlying molecular mechanism. We found that IDE was widely expressed in porcine tissues, including kidney, lung, spleen, liver, heart, and skeletal muscle. Then, to explore the effects of IDE on the proliferation and apoptosis of PSMSCs, we subjected the cells to siRNA-mediated knockdown of IDE expression, which resulted in promoted cell proliferation and reduced apoptosis. As one of key transcription factors in myogenesis, MYOD, its expression was also decreased with IDE knockdown. To further elucidate the underlying molecular mechanism, RNA sequencing was performed. Among transcripts perturbed by the IDE knockdown after, a downregulated gene myostatin (MSTN) which is known as a negative regulator for muscle growth attracted our interest. Indeed, MSTN knockdown led to similar results as those of the IDE knockdown, with upregulation of cell cycle-related genes, downregulation of MYOD as well as apoptosis-related genes, and enhanced cell proliferation. Taken together, our findings suggest that IDE regulates the proliferation and apoptosis of PSMSCs via MSTN/MYOD pathway. Thus, we recruit IDE to the gene family of regulators for porcine skeletal muscle development and propose IDE as an example of gene to prioritize in order to improve pork production.

1695 Undergraduate Cardiothoracic Surgery: Pumping Up Knowledge and Inspiration with High-Fidelity Simulation

Abstract Introduction Alongside declining ST3 applications, cardiothoracic surgery (CTS) is underrepresented in the medical curriculum with 90% of medical students reporting no exposure to the specialty in medical school placements. This may result in clinicians having difficulties recognising emergency presentations, with subsequent referrals made inappropriately. Method A simulation course involving teaching around common CTS conditions and procedures was delivered by CTS trainees to undergraduate medical students (n = 50). This involved both theory and high-fidelity simulations of coronary anastomoses using cardiac surgical equipment on porcine hearts and ureters. Delegates were given pre and post-test questionnaires, and another at six-weeks to test knowledge retention. Results were statistically analysed using paired and independent sample t-tests. Results Delegates demonstrated significant improvements in post-test knowledge of 56% (p&amp;lt;0.01), and sustained improvement of 51% (p&amp;lt;0.01) six-weeks later compared to baseline. 64% of delegates reported an increased interest in pursuing CTS as a career; 40% reported improved confidence performing a coronary anastomosis. Conclusions Immediate and long-term knowledge retention of key CTS concepts and ability to assess common CTS pathological scenarios were demonstrated in this study. CTS simulation therefore represents an effective mechanism by which key concepts can be taught to undergraduate medical students, whilst enhancing interest in pursuing CTS as a career. As an educational adjunct, simulation can help bridge the gap between taught theory and applied practice, with the potential to empower future doctors to make more informed referrals and management decisions.

PSVI-26 Optimized small tissue specific protein isolation trough complexed diafiltration technique

Abstract Physiologically active and pure small tissue specific proteins are in demand in various fundamental and applied areas due to its bioactive properties. It is known that proteins can aggregate, as well as form a highly concentrated layer at the border of the filtration membrane or adhere to it, which significantly interferes with filtration. To eliminate these effects, protein-peptide extracts are recommended to be diluted, as well as using special agents, among them amino acids are more suitable for food industry. The purpose of the study is to develop the isolation and purification of proteins with molecular weight lower 50kDa from porcine hearts and aortas, using different amino acids and its combination. It was previously revealed, that family of fatty acid binding proteins (FABP) is one of the most stable and physiologically active protein in such raw materials. The final technology includes extraction, centrifugation, dilution of extract, diafiltration, lyophilization, dissolving in a small volume of distilled water, dialization and final drying. Concentration of 1.0% glycine and 0.1M proline in both diluted extract and exchange solution was revealed to be most effective to prevent protein aggregation. Dialysates were dried lyophilically and O’Farrell 2DE-electrophoresis with MALDI-TOF MS and MS/MS mass spectrometry identification were used. No proteins of 50kDa and bigger were detected. Proteins of lipid metabolism, peroxiredoxin 2, transgelins etc. with molecular weight lower 50kDa were found. The developed technology allows increasing cardiac and adipocytic isoforms of FABP family content. Cardiac isoform was previously identified in raw material, while adipocytic was newly detected. Adipocytic isoform content is lower than cardiac one; therefore, it was not detected in raw material, but application of complexed diafiltration technique led to increasing its content in dialysate. The developed technology can be used for separation and purification of animal proteins in native and stable forms.

Relationship of Laser-Doppler-Flow and coronary perfusion and a concise update on the importance of coronary microcirculation in donor heart machine perfusion.

Machine perfusion (MP) is a novel method for donor heart preservation. The coronary microvascular function is important for the transplantation outcome. However, current research on MP in heart transplantation focuses mainly on contractile function. We aim to present the application of Laser-Doppler-Flowmetry to investigate coronary microvascular function during MP. Furthermore, we will discuss the importance of microcirculation monitoring for perfusion-associated studies in HTx research. Porcine hearts were cardioplegically arrested and harvested (Control group, N = 4). In an ischemia group (N = 5), we induced global ischemia of the animal by the termination of mechanical ventilation before harvesting. All hearts were mounted on an MP system for blood perfusion. After 90 minutes, we evaluated the effect of coronary perfusion pressures from 20 to 100 mmHg while coronary laser-doppler-flow (LDF) was measured. Ischemic hearts showed a significantly decreased relative LDF compared to control hearts (1.07±0.06 vs. 1.47±0.15; p = 0.034). In the control group, the coronary flow was significantly lower at 100 mmHg of perfusion pressure than in the ischemia group (895±66 ml vs. 1112±32 ml; p = 0.016). Laser-Doppler-Flowmetry is able to reveal coronary microvascular dysfunction during machine perfusion of hearts and is therefore of substantial interest for perfusion-associated research in heart transplantation.

Impedance fluctuation and steam pop occurrence during radiofrequency current ablation: An experimental in vitro model.

The radiofrequency impedance measurement is one of the basic parameters monitored during ablation procedures. An abrupt rise in impedance is often observed corresponding to a steam pop. The exact correlation between the occurrence of steam pop and subsequent rise in impedance has not been experimentally described so far. To evaluate the relationship between steam pop occurrence and impedance fluctuations observed during radiofrequency ablation (RFA). Porcine heart tissue specimens were appropriately prepared and placed in an experimental setup connected to electrophysiological equipment with 3D anatomical mapping facilities. The RFA lesions were performed in standardized conditions with the use of contact force measurement-enabled open irrigation ablation catheter (ThermoCool SmartTouch™, 3.5 mm tip, F-J curvature; Biosense Webster, Irvine, USA) in the power-control mode. The RFA delivery was stopped when the steam pop occurred. Time taken for the steam pop to occur and to the subsequent abrupt impedance rise was recorded, along with the impedance fluctuations during an application. In total, 25 experimental radiofrequency (RF) current deliveries ended up with steam pops, which occurred after 30-60 s. The time recorded from the beginning of the application up to the steam pop was shorter if increased power was applied (35 W compared to 30 W: 41.5 ±9.9 s compared to 49.9 ±8.2 s; p = 0.046). During all RF applications, impedance significantly but gradually decreased from 122.9 ±7.9 Ω to 87.5 ±3.6 Ω (p < 0.001) with a mean drop rate of 0.8 ±0.2 Ω/s. During all experiments, the abrupt and significant impedance increase (8.2 ±2.0 Ω, p < 0.001) was observed always after steam pop occurrence (207.4 ±155.9 ms). During RF current delivery which ended up with steam pop, an abrupt impedance increase was always registered after the occurrence of this phenomenon. Therefore, the impedance rise observed during steam popping cannot be used for its prediction. The time to steam pop was shorter for applications with increased power but not with greater contact force.

Vasa nervorum of epicardial nerves and valves of small veins investigated in porcine heart by two types of vascular injections.

The morphology of the vascular supply of peripheral branches of cardiac nerves has not been systematically described until now. The aim of this study was to describe the architectonics of the vasa nervorum of epicardial nerves in porcine hearts by using two injection techniques. Twenty-three hearts from young healthy pigs were used. In 10 hearts India ink solution was injected into the origin of the anterior interventricular branch. In another 10 hearts India ink solution was injected retrogradely through the coronary sinus. The hearts were then analyzed using a magnifying glass and light microscopy. The arterial injection showed the entirety of the rich venous components of the vasa nervorum, which often consisted of paired veins accompanying the epicardial nerves. The thickness of the nerves ranged from 50 to 815 μm. The vasa nervorum drained into larger subepicardial veins. In seven of the hearts prepared with venous injections the vasa nervorum of epicardial nerves were visualized in the same detail as in the arterial preparations and India ink solution filled the right ventricle via the smallest cardiac veins. The histological analysis of these seven hearts showed complete dehiscence and functional insufficiency of small and larger veins valves. In the other three hearts prepared with venous injections the valves were competent, which prevented retrograde filling of larger and smaller veins. The results obtained expand the current knowledge on epicardial nerves vasa nervorum and provide anatomical evidence behind the mechanism of retrograde application of cardioplegic solutions in cardiac surgery.

Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle ‘metabolon’ which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was present together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.

Catheter contact area strongly correlates with lesion area in radiofrequency cardiac ablation: an ex vivo porcine heart study

PurposeOur previous study confirmed that not only force but also the catheter contact angle substantially impacted the contact area and its morphology. Therefore, in this study, we aimed to further investigate the relationship between the catheter contact area and the dimensions of the ablation lesion area as a function of catheter contact angle and force in radiofrequency catheter ablation.MethodsThe radiofrequency catheter ablation test was performed for 5 contact angles and 8 contact forces at a fixed ablation time of 30 s. The initial impedance was 92.5 ± 2.5 Ω, the temperature during ablation was 30 °C, and the power was 30 W. The irrigation rate during ablation was set to 17 mL/min. Each experiment was repeated 6 times.ResultsThe catheter contact area showed a strong correlation with the ablation lesion area (r = 0.8507). When the contact area was increased, the lesion area also increased linearly in a monotonic manner. The relationships between catheter contact force and ablation lesion area and between catheter contact force and ablation lesion depth are logarithmic functions in which increased contact force was associated with increased lesion area and depth. The catheter contact angle is also an important determinant of the lesion area. The lesion area progressively increased when the contact angle was decreased. In contrast, the lesion depth progressively increased when the contact angle was increased.ConclusionsThe catheter contact area was strongly correlated with the ablation lesion area. Additionally, catheter contact force and contact angle significantly impacted the dimensions of the lesion in radiofrequency catheter ablation procedures.

Abstract MP254: Decellularized Extracellular Matrix Hydrogel Lowers Fibrosis And Fibroblast Differentiation In Post-injury Mice Hearts Through Capg

Hypothesis and objective: We hypothesize that transplantation of decellularized cardiac extracellular matrix (dECM) lowers fibrosis and fibroblast differentiation. In this study we investigated collagen deposition and fibroblast differentiation in post-MI hearts and heart explants of various stiffness after dECM hydrogel treatments. The objectives are 1) determining if dECM derived from fetal and adult porcine hearts reduces fibrosis in injured hearts; and 2) identifying specific signaling pathways that regulate fibroblasts differentiation induced by extracellular proteins. Methods: Porcine dECM was injected immediately after ligating coronary artery in P1 mice. Histology was conducted on day 7 post-myocardial infarction (MI). A mice ventricle explant model was used to investigate the molecular mechanisms. Results: We observed that fetal dECM treatment lowered fibrosis and fibroblast differentiation in post-MI hearts (Fig.1). Fibroblast differentiation as indicated by α-smooth muscle actin expression in vimentin or platelet derived growth factor receptor α positive cells showed an inhibitory effect of fetal dECM on fibroblast differentiation. Using a heart explant model of modulated microenvironment stiffness, we demonstrated that increasing tissue stiffness stimulates fibroblast differentiation and collagen deposition. Fetal dECM treatment, however, inhibited fibroblast differentiation induced by increasing microenvironment stiffness. Transcriptome analysis revealed that two cytoskeleton-related genes, macrophage capping protein (CAPG) and leupaxin (LPXN), are modulated by dECM treatments. Using cytoskeleton polymerization modulators and siRNA, we demonstrated that fetal dECM lowers fibroblast differentiation through CAPG.

Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart

Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a considerable proportion of coronary artery disease patients remain symptomatic. Gene therapy-mediated therapeutic angiogenesis offers a novel therapeutic method for improving myocardial perfusion and relieving symptoms. Gene therapy with different angiogenic factors has been studied in few clinical trials. Due to the novelty of the method, the progress of myocardial gene therapy is a continuous path from bench to bedside. Therefore, large animal models are needed for evaluating the safety and efficacy. The more the large animal model identifies the original disease and the endpoints used in clinics, the more predictable outcomes are from clinical trials. Here, we introduce a large animal model for evaluating the efficacy of the gene therapy in the ischemic porcine heart. We use clinically relevant imaging methods such as ultrasound imaging and 15H2O-PET. For targeting the gene transfers into the desired area, electroanatomical mapping is used. The aim of this method is: (1) to mimic chronic coronary artery disease, (2) to induce therapeutic angiogenesis at hypoxic areas of the heart, and (3) to evaluate the safety and efficacy of the gene therapy by using relevant endpoints.

Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart.

Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a considerable proportion of coronary artery disease patients remain symptomatic. Gene therapy-mediated therapeutic angiogenesis offers a novel therapeutic method for improving myocardial perfusion and relieving symptoms. Gene therapy with different angiogenic factors has been studied in few clinical trials. Due to the novelty of the method, the progress of myocardial gene therapy is a continuous path from bench to bedside. Therefore, large animal models are needed for evaluating the safety and efficacy. The more the large animal model identifies the original disease and the endpoints used in clinics, the more predictable outcomes are from clinical trials. Here, we introduce a large animal model for evaluating the efficacy of the gene therapy in the ischemic porcine heart. We use clinically relevant imaging methods such as ultrasound imaging and 15H2O-PET. For targeting the gene transfers into the desired area, electroanatomical mapping is used. The aim of this method is: (1) to mimic chronic coronary artery disease, (2) to induce therapeutic angiogenesis at hypoxic areas of the heart, and (3) to evaluate the safety and efficacy of the gene therapy by using relevant endpoints.

Commissural repositioning in bicuspid aortic valve repair: an in vitro acute model to explore and explain different results.

Commissural orientation <160° is a recognized risk factor for bicuspid aortic valve repair failure. Based on this observation, repairing this subtype of aortic valve by reorienting the 2 commissures at 180° has recently been proposed. Nine porcine hearts with aortic annulus diameters of 25 mm were selected. A pathological model of a Sievers 1 bicuspid aortic valve was obtained by suturing the coaptation line between the left and right leaflets. Each heart underwent reimplantation procedures both in the native (120°) and the reoriented (180°) configuration. After the operation, each sample was tested on a pulse duplicator at rest (heart rate 60 beats per min) and with mild exercise (heart rate 90 beats per min) conditions. No statistically significant difference was noted in mean and peak transvalvular aortic gradients between the 2 configurations at rest (18.6 ± 5 vs 17.5 ± 4 for the mean aortic gradient; 42.8 ± 12.7 vs 36.3 ± 5.8 for the peak aortic gradient) but the group with the 120°-oriented commissures had significantly higher mean transaortic gradients compared to the group with the 180°-oriented commissures at initial exercise stress conditions (30.1 ± 9.1 vs 24.9 ± 3.8; p value 0.002). The 180° commissural reorientation of the asymmetrical bicuspid aortic valve does not improve the transvalvular aortic gradient in an acute model at rest conditions, but it could do so under stress situations. Even if it is surgically more complex and time-consuming, this approach could be a good strategy to improve long-term results, particularly in young patients.

B-IN01-03 FOCUSED ELECTRIC FIELD ABLATION: A NOVEL ABLATION TECHNOLOGY INCREASES ABLATION LESION DEPTH WITH IMPROVED SAFETY

RF ablation has limited ability to deliver deep lesions, as most of the energy is dissipated in the first few mm of tissue from the catheter and lesion expansion occurs by conduction of heat. Focused Electric Field (FEF) is a novel technology using a concave-tipped catheter to create an electric field that falls off slowly with distance, increasing the amount of tissue ablated by resistive heating. FEF technology has the potential to create deeper lesions while avoiding the risk of steam pops. To introduce FEF technology and demonstrate its feasibility as an ablation tool. Using an FEF catheter we performed ablation in ex vivo porcine left ventricles, using real-time infrared imaging as well as tissue histology to monitor lesion formation and compare FEF to Thermocool catheters. We tested our FEF catheter by ablating in ex vivo porcine hearts. The FEF catheter was able to create deeper lesions (15.2±1.1mm deep at 20W compared to 6.1±1.0mm for Thermocool at 40W). Steam pops were less frequent with FEF technology (6.7% vs. 37.5%). Real-time thermal imaging shows that in contrast to an irrigated tip RF catheter which generates high temperatures near the catheter tip, FEF generates a more uniform temperature profile down to depths of over 15mm with few areas of high temperatures. FEF ablation creates lesions with a more uniform temperature profile and avoids overheating of tissue thus allowing much deeper lesion formation with a lower risk of steam pops. Compared to RF technology, FEF ablation has the potential to allow significantly deeper ablation than current technology with an improved safety margin.

B-PO03-122 DELINEATION OF 3D REENTRANT CIRCUITS USING EPICARDIAL-ENDOCARDIAL ELECTROCARDIOGRAPHIC IMAGING

Studies of VT mechanisms are largely based on a 2D portrait of reentrant circuits on one surface of the heart. This oversimplifies the 3D circuit that involves the depth of the myocardium. Simultaneous epicardial and endocardial (epi-endo) mapping was shown to facilitate a 3D delineation of VT circuits, which is however difficult via invasive mapping. We study the feasibility of noninvasive epi-endo electrocardiographic imaging (ECGi) in delineating 3D VT circuits. 120-lead ECGs of VT in combination with subject-specific heart-torso geometry are used to compute unipolar electrograms (CEGM) on ventricular epicardium and endocardia. Activation isochrones are constructed, and the percentage of activation within VT cycle length is calculated on each surface. This classifies VT circuits into 2D (surface only), uniform transmural, nonuniform transmural, and mid-myocardial (focal on surfaces). Critical circuit components, including exits and central isthmuses, are further localized. We analyzed 23 simulated and four in-vivo VT circuits on post-infarction porcine hearts. In simulated circuits, ECGi classified 21% as 2D and 78% as 3D: 82.6% of these were correctly classified (see Fig 1). In in-vivo circuits, ECGi classified 25% as 2D and 75% as 3D: in all cases, circuit exits and entrances were consistent with potential critical isthmus delineated from combined LGE-MRI and catheter mapping data. ECGi epi-endo mapping has the potential for fast delineation of 3D VT circuits, which may augment detailed catheter mapping for VT ablation.

B-PO01-014 FOCUSED ELECTRIC FIELD ABLATION: A NOVEL ABLATION TECHNOLOGY INCREASES ABLATION LESION DEPTH WITH IMPROVED SAFETY

RF ablation has limited ability to deliver deep lesions, as most of the energy is dissipated in the first few mm of tissue from the catheter and lesion expansion occurs by conduction of heat. Focused Electric Field (FEF) is a novel technology using a concave-tipped catheter to create an electric field that falls off slowly with distance, increasing the amount of tissue ablated by resistive heating. FEF technology has the potential to create deeper lesions while avoiding the risk of steam pops. To introduce FEF technology and demonstrate its feasibility as an ablation tool. Using an FEF catheter we performed ablation in ex vivo porcine left ventricles, using real-time infrared imaging as well as tissue histology to monitor lesion formation and compare FEF to Thermocool catheters. We tested our FEF catheter by ablating in ex vivo porcine hearts. The FEF catheter was able to create deeper lesions (15.2±1.1mm deep at 20W compared to 6.1±1.0mm for Thermocool at 40W). Steam pops were less frequent with FEF technology (6.7% vs. 37.5%). Real-time thermal imaging shows that in contrast to an irrigated tip RF catheter which generates high temperatures near the catheter tip, FEF generates a more uniform temperature profile down to depths of over 15mm with few areas of high temperatures. FEF ablation creates lesions with a more uniform temperature profile and avoids overheating of tissue thus allowing much deeper lesion formation with a lower risk of steam pops. Compared to RF technology, FEF ablation has the potential to allow significantly deeper ablation than current technology with an improved safety margin.