Swine Hearts Research Articles

Right ventricular insertion promotes reinitiation of ventricular fibrillation in defibrillation failure

Shocks near defibrillation threshold (nDFT) strength commonly extinguish all ventricular fibrillation (VF) wavefronts, but a train of rapid, well-organized postshock activations (PAs) typically appears before sinus rhythm ensues. If one of the PA waves undergoes partial propagation block (wavebreak), reentry may be induced, causing VF to reinitiate and the shock to fail. The purpose of this study was to determine whether wavebreak leading to VF reinititation following nDFT shocks occurs preferentially at the right ventricular insertion (RVI), which previous studies have identified as a key site for wavebreak. We used panoramic optical mapping to image the ventricular epicardium of 6 isolated swine hearts during nDFT defibrillation episodes. After each experiment, the hearts were fixed and their geometry scanned with magnetic resonance imaging (MRI). The MRI and mapping datasets were spatially coregistered. For failed shocks, we identified the site of the first wavebreak of a PA wave during VF reinitiation. We recorded 59 nDFT failures. In 31 of these, the first wavebreak event occurred within 1 cm of the RVI centerline, most commonly on the anterior side of the right ventricular insertion (aRVI) (23/31). The aRVI region occupies 16.8% ± 2.5% of the epicardial surface and would be expected to account for only 10 wavebreaks if they were uniformly distributed. By χ2 analysis, aRVI wavebreaks were significantly overrepresented. The anterior RVI is a key site in promoting nDFT failure. Targeting this site to prevent wavebreak could convert defibrillation failure to success and improve defibrillation efficacy.

4D Printing of Bioinspired Absorbable Left Atrial Appendage Occluders: A Proof-of-Concept Study.

The significant mismatch of mechanical properties between the implanted medical device and biological tissue is prone to cause wear and even perforation. In addition, the limited biocompatibility and nondegradability of commercial Nitinol-based occlusion devices can easily lead to other serious complications, such as allergy and corrosion. The present study aims to develop a 4D printed patient-specific absorbable left atrial appendage occluder (LAAO) that can match the deformation of left atrial appendage (LAA) tissue to reduce complications. The desirable bioinspired network is explored by iterative optimization to mimic the stress-strain curve of LAA tissue and LAAOs are designed based on the optimal network. In vitro degradation tests are carried out to evaluate the effects of degradation on mechanical properties. In addition, 48 weeks of long-term subcutaneous implantation of the occluder shows favorable biocompatibility, and the 20-cycle compression test demonstrates outstanding durability of LAAO. Besides, a rapid, complete, and remote-controlled 4D transformation process of LAAO is achieved under the trigger of the magnetic field. The deployment of the LAAO in an isolated swine heart initially exhibits its feasibility for transcatheter LAA occlusion. To the best of our knowledge, this is the first demonstration of the 4D printed LAA occlusion device. It is worth noting that the bioinspired design concept is not only applicable to occlusion devices, but also to many other implantable medical devices, which is conducive to reducing complications, and a broad range of appealing application prospects can be foreseen.

UPGRADE OF THE LANGENDORFF APPARATUS USING THE INFRARED THERMO-CONTROL SYSTEM AND AN INTELLIGENT HEATER

Biological experiments involving isolated organs and tissues demand precise temperature monitoring and regulation. An automatic temperature control system was proposed and optimised on real isolated swine hearts and the prototype is described in this work. The traditional Langendorff apparatus consists of a heart holder, a reservoir of perfusion solution flowing to aortic cannula and a heating bath allowing passive heat transfer to the reservoir of perfusion solution. The commercial infrared camera FLIR T62101 was added to this basic set-up and used for very precise monitoring of the temperature kinetic of the organ and connected with an electronic feedback loop, which allowed real-time and precise regulation of heat transfer from the heating bath to the perfusion solution and in turn indirectly to the heart tissue. This provides real time control and active regulation of the myocardial tissue temperature. The infrared camera was tested in several modes and several variants of detection were optimised for ideal measurement of the region of interest of the ex vivo organ. The kinetics of the temperature changes and temperature stability of the tissue were recorded and calibrated by external electronic thermometers (type Pt100, inserted in tissue). The time lapse from the hang-up of the hypo termed organ (30 °C) until optimal warming (37 °C) was less than eight minutes in the final instrument prototype. The final stability of the 37 °C tissue temperature was approved; the temperature fluctuation of left ventricle tissue was characterised as 36.8 ± 0.5 °C. This upgraded traditional instrument could be used in specific preclinical and clinical transplantation and analytical projects in future.

Impact of Catheter Contact Angle on Lesion Formation and Durability of Pulmonary Vein Isolation

Objectives: This study aimed to evaluate the impact of catheter contact angle on lesion formation and durability of pulmonary vein isolation (PVI). Background: Little is known on the effect of catheter contact angle on lesion formation and durability of PVI. Methods: Both in vitro experiment and retrospective observational study were conducted. For in vitro experiment, radiofrequency lesions were created on explanted swine hearts in three different catheter contact angles (0{degree sign}, 45{degree sign}, and 90{degree sign}). In the retrospective observational study, we assessed patients who had undergone repeat catheter ablation due to atrial fibrillation recurrence after initial PVI. When pulmonary vein (PV) reconnection was observed, we analyzed the previous ablation points within and without the gap area. The gap areas were where ablation had changed the PV activation sequence or eliminated the PV potential in the repeat session. Results: In the in vitro experiment, lesion width was the smallest (5.3 {plus minus} 0.4 mm) in perpendicular contact compared to 0{degree sign} (vs 5.8 {plus minus} 0.5 mm, p=0.040) and 45{degree sign} (vs 6.4 {plus minus} 0.4 mm, p<0.001). In the retrospective observational study, we assessed 666 tags of 16 patients with PV reconnections, and 60 tags were in the gap area. Tags in the gap area had longer interlesion distance (odds ratio [OR] 1.49, p < 0.001), greater contact force variability (OR 1.03, p = 0.008), and higher rate of perpendicular contact (OR 3.26, p < 0.001) on multivariate analysis. Conclusion:Perpendicular contact was associated with a smaller lesion and higher rate of PV reconnection

On the Role of Ionic Modeling on the Signature of Cardiac Arrhythmias for Healthy and Diseased Hearts

Computational cardiology is rapidly becoming the gold standard for innovative medical treatments and device development. Despite a worldwide effort in mathematical and computational modeling research, the complexity and intrinsic multiscale nature of the heart still limit our predictability power raising the question of the optimal modeling choice for large-scale whole-heart numerical investigations. We propose an extended numerical analysis among two different electrophysiological modeling approaches: a simplified phenomenological one and a detailed biophysical one. To achieve this, we considered three-dimensional healthy and infarcted swine heart geometries. Heterogeneous electrophysiological properties, fine-tuned DT-MRI -based anisotropy features, and non-conductive ischemic regions were included in a custom-built finite element code. We provide a quantitative comparison of the electrical behaviors during steady pacing and sustained ventricular fibrillation for healthy and diseased cases analyzing cardiac arrhythmias dynamics. Action potential duration (APD) restitution distributions, vortex filament counting, and pseudo-electrocardiography (ECG) signals were numerically quantified, introducing a novel statistical description of restitution patterns and ventricular fibrillation sustainability. Computational cost and scalability associated with the two modeling choices suggests that ventricular fibrillation signatures are mainly controlled by anatomy and structural parameters, rather than by regional restitution properties. Finally, we discuss limitations and translational perspectives of the different modeling approaches in view of large-scale whole-heart in silico studies.

Transesophageal echocardiography in swine: evaluation of left and right ventricular structure, function and myocardial work

This study aimed to determine standard left (LV) and right ventricular (RV) transesophageal echocardiographic (TEE) measurements in swine. Additionally, global myocardial work index (GWI) was estimated using pressure-strain loops (PSL). A comprehensive TEE examination was conducted in ten anesthetized, intubated and mechanically ventilated healthy female German landrace swine, weighing 44 to 57 kg. For GWI calculation, we performed LV and RV segmental strain analysis and used invasively measured LV and RV pressure to obtain PSL. The GWI and further myocardial work indices were calculated from the area of the PSL using commercially available software. Furthermore, hemodynamic measurements were obtained using indwelling catheters. We obtained complete standardized baseline values for left and right ventricular dimensions and function. Biplane LV ejection fraction was 63 ± 7 % and the LV end-diastolic volume was 70.5 ± 5.9 ml. Tissue Doppler estimated peak tricuspid annular systolic velocity was 13.1 ± 1.8 cm/s. The Doppler estimated LV and RV stroke volume index were 75.6 ± 7.2 ml/m2 and 76.7 ± 7.8 ml/m2 respectively. Pulsed wave Doppler derived cardiac output correlated well with cardiac output estimated using the thermodilution method (7.0 ± 1.2 l/min vs. 7.0 ± 1.1 l/min, r = 0.812, p = 0.004). The LV global longitudinal strain was -21.3 ± 3.9 % and the RV global longitudinal strain was -15.4 ± 2.5 %. LV GWI was 1885(1281–2121) mmHg*% and 297 ± 62 mmHg*% for the RV. LV global myocardial work efficiency was 82.6 ± 4 % and 83(72–88) % for the RV. TEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. Myocardial contractility and mechanics can be reliably evaluated with the non-invasive GWI derived from echocardiography without additional invasive measures.

1,5-Disubstituted-1,2,3-triazoles as inhibitors of the mitochondrial Ca2+ -activated F1 FO -ATP(hydrol)ase and the permeability transition pore.

The mitochondrial permeability transition pore (mPTP), a high-conductance channel triggered by a sudden Ca2+ concentration increase, is composed of the F1 FO -ATPase. Since mPTP opening leads to mitochondrial dysfunction, which is a feature of many diseases, a great pharmacological challenge is to find mPTP modulators. In our study, the effects of two 1,5-disubstituted 1,2,3-triazole derivatives, five-membered heterocycles with three nitrogen atoms in the ring and capable of forming secondary interactions with proteins, were investigated. Compounds 3a and 3b were selected among a wide range of structurally related compounds because of their chemical properties and effectiveness in preliminary studies. In swine heart mitochondria, both compounds inhibit Ca2+ -activated F1 FO -ATPase without affecting F-ATPase activity sustained by the natural cofactor Mg2+ . The inhibition is mutually exclusive, probably because of their shared enzyme site, and uncompetitive with respect to the ATP substrate, since they only bind to the enzyme-ATP complex. Both compounds show the same inhibition constant (K'i ), but compound 3a has a doubled inactivation rate constant compared with compound 3b. Moreover, both compounds desensitize mPTP opening without altering mitochondrial respiration. The results strengthen the link between Ca2+ -activated F1 FO -ATPase and mPTP and suggest that these inhibitors can be pharmacologically exploited to counteract mPTP-related diseases.

Abstract 342: Cortical Bone Stem Cell Therapy Alters Macrophage Phenotype and Reduces Cardiac Cell Death After Myocardial Infarction

Acute injuries to the heart, like myocardial infarction (MI), contribute to the development and pathology of heart failure (HF). Reperfusion of the ischemic heart greatly increases survival but results in reperfusion injury that can account for up to 50% of the final infarct size. The inflammatory response to MI-induced myocardial injury is thought to be responsible for the propagation of reperfusion injury into the infarct border zone, expanding myocardial damage. We have previously shown in a swine model of MI that intramyocardial injections of cortical bone-derived stem cells (CBSCs) into the infarct border zone has no acute cardioprotective effect but reduces scar size by half and prevents the decline of ejection fraction and LV dilation 3 months after MI. Our new preliminary data show that CBSCs have potent immunoregulatory capabilities. Therefore, we hypothesize that CBSC treatment has an effect on the immune response to MI that improves the wound healing response to myocardial injury and mitigates LV remodeling and infarct size 3 months later. To test this hypothesis, we characterized the effects of CBSC paracrine factors on macrophages in vitro and found that CBSC-treated macrophages express higher levels of CD206, produce more IL-1RA and IL-10, and phagocytose apoptotic myocytes more efficiently. In addition, macrophages were increased in CBSC-treated swine hearts 7 days after MI compared to controls with a corresponding increase in IL-1RA and TIMP-2. Apoptosis was decreased overall and in macrophages specifically in CBSC-treated animals. From these data we conclude CBSCs may exert an acute pro-reparative effect on the immune response after MI, reducing reperfusion injury and adverse remodeling resulting in improved functional outcomes at later time points.

In-silico study of the cardiac arrhythmogenic potential of biomaterial injection therapy

Biomaterial injection is a novel therapy to treat ischemic heart failure (HF) that has shown to reduce remodeling and restore cardiac function in recent preclinical studies. While the effect of biomaterial injection in reducing mechanical wall stress has been recently demonstrated, the influence of biomaterials on the electrical behavior of treated hearts has not been elucidated. In this work, we developed computational models of swine hearts to study the electrophysiological vulnerability associated with biomaterial injection therapy. The propagation of action potentials on realistic biventricular geometries was simulated by numerically solving the monodomain electrophysiology equations on anatomically-detailed models of normal, HF untreated, and HF treated hearts. Heart geometries were constructed from high-resolution magnetic resonance images (MRI) where the healthy, peri-infarcted, infarcted and gel regions were identified, and the orientation of cardiac fibers was informed from diffusion-tensor MRI. Regional restitution properties in each case were evaluated by constructing a probability density function of the action potential duration (APD) at different cycle lengths. A comparative analysis of the ventricular fibrillation (VF) dynamics for every heart was carried out by measuring the number of filaments formed after wave braking. Our results suggest that biomaterial injection therapy does not affect the regional dispersion of repolarization when comparing untreated and treated failing hearts. Further, we found that the treated failing heart is more prone to sustain VF than the normal heart, and is at least as susceptible to sustained VF as the untreated failing heart. Moreover, we show that the main features of VF dynamics in a treated failing heart are not affected by the level of electrical conductivity of the biogel injectates. This work represents a novel proof-of-concept study demonstrating the feasibility of computer simulations of the heart in understanding the arrhythmic behavior in novel therapies for HF.

A Novel Quantitative Ex Vivo Model of Functional Mitral Regurgitation.

Durability of mitral valve (MV) repair for functional mitral regurgitation (FMR) remains suboptimal. We sought to create a highly reproducible, quantitative ex vivo model of FMR that functions as a platform to test novel repair techniques. Fresh swine hearts (n = 10) were pressurized with air to a left ventricular pressure of 120 mmHg. The left atrium was excised and the altered geometry of FMR was created by radially dilating the annulus and displacing the papillary muscle tips apically and radially in a calibrated fashion. This was continued in a graduated fashion until coaptation was exhausted. Imaging of the MV was performed with a 3-dimensional (3D) structured-light scanner, which records 3D structure, texture, and color. The model was validated using transesophageal echocardiography in patients with normal MVs and severe FMR. Compared to controls, the anteroposterior diameter in the FMR state increased 32% and the annular area increased 35% (P < 0.001). While the anterior annular circumference remained fixed, the posterior circumference increased by 20% (P = 0.026). The annulus became more planar and the tenting height increased 56% (9 to 14 mm, P < 0.001). The median coaptation depth significantly decreased (anterior leaflet: 5 vs 2 mm; posterior leaflet: 7 vs 3 mm, P < 0.001). The ex vivo normal and FMR models had similar characteristics as clinical controls and patients with severe FMR. This novel quantitative ex vivo model provides a simple, reproducible, and inexpensive benchtop representation of FMR that mimics the systolic valvular changes of patients with FMR.

Intra-myocardial alginate hydrogel injection acts as a left ventricular mid-wall constraint in swine

Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n = 5), ischemic HF (n = 5), and ischemic HF treated with alginate hydrogel injection therapy (n = 5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.68 ± 0.10μm [treated] vs. 1.78 ± 0.15μm [untreated], p<0.001). Systolic contractility in treated animals improved substantially (ejection fraction = 43.9 ± 2.8% [treated] vs. 34.7 ± 2.7% [untreated], p<0.01). The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. Statement of SignificanceHeart failure is considered a growing epidemic and hence an important health problem in the US and worldwide. Its high prevalence (5.8 million and 23 million, respectively) is expected to increase by 25% in the US alone by 2030. Heart failure is associated with high morbidity and mortality, has a 5-year mortality rate of 50%, and contributes considerably to the overall cost of health care ($53.1 billion in the US by 2030). Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge concerning the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To understand the mechanism of action, we combined high-resolution ex vivo magnetic resonance imaging and histological data in swine with state-of-the-art subject-specific computational model simulations. The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as a left ventricular mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated heart failure controls without causing negative secondary outcomes to cardiac function. Moreover, if the hydrogel can be delivered percutaneously rather than via the currently used open-chest procedure, this therapy may become routine for heart failure treatment. A minimally invasive procedure would be in the best interest of this patient population; i.e., one that cannot tolerate general anesthesia and surgery, and it would be significantly more cost-effective than surgery.

Pharmacological Conditioning Reduces Damage from Ischemia-Reperfusion Injury in Porcine Skeletal Muscle and Ex-Vivo Functional Hearts

Heart transplantation is commonly considered to be the only option available for patients with congenital heart defects and/or individuals with terminal heart failure. Myocardial ischemia-reperfusion injury (IRI) can damage the heart and prolong recovery. Common complications of IRI include graft rejection, cardiac allograft vasculopathy, graft dysfunction, and chronic kidney disease. Solutions of omega-3/omega-6 fatty acids and bear bile acids have been found to attenuate IRI. This study observes the protection conferred by these agents in isolated muscle bundles as well as on ex-vivo perfused hearts METHODS: Diaphragm skeletal muscle bundles are harvested from swine. Each individual bundle is placed in an isolated tissue bath measuring twitch force. Muscle bundles are stimulated and the force of contraction is recorded. Baseline and pretreatment data is collected for 1 hour each. Following pretreatment nitrogen gas is bubbled to induce hypoxia. Recovery force data is collected for 5 hours. Recorded data is normalized to baseline and analyzed.Additionally, swine hearts were pretreated for 1 hour before explant and subsequent reanimation on the Visible Heart Apparatus. Left ventricular pressure was collected for 2 hours post-reanimation. Preliminary results indicate pretreatment protects and increases muscle contractile function compared to controls. Increased function was observed in bundles that received omega-3 and omega-6 treatment before hypoxia and improved recovery was observed when combined with bear bile acids. Reanimated hearts show an increased left ventricular pressure differential after pretreatment CONCLUSION: The preliminary investigations in diminishing IRI suggest there are promising applications of omega-3, omega-6, and bear bile acid treatments, specifically in heart transplantation.

Creatine kinase rate constant in the human heart at 7T with 1D-ISIS/2D CSI localization.

PurposeCreatine Kinase (CK) reaction plays an important role in energy metabolism and estimate of its reaction rate constant in heart provides important insight into cardiac energetics. Fast saturation transfer method ( nominal) to measure CK reaction rate constant (kf) was previously demonstrated in open chest swine hearts. The goal of this work is to further develop this method for measuring the kf in human myocardium at 7T. approach is combined with 1D-ISIS/2D-CSI for in vivo spatial localization and myocardial CK forward rate constant was then measured in 7 volunteers at 7T.Methods method uses two partially relaxed saturation transfer (ST) spectra and correction factor to determine CK rate constant. Correction factor is determined by numerical simulation of Bloch McConnell equations using known spin and experimental parameters. Optimal parameters and error estimate in calculation of CK reaction rate constant were determined by simulations. The technique was validated in calf muscles by direct comparison with saturation transfer measurements. pulse sequence was incorporated with 1D-image selected in vivo spectroscopy, combined with 2D-chemical shift spectroscopic imaging (1D-ISIS/2D-CSI) for studies in heart. The myocardial CK reaction rate constant was then measured in 7 volunteers.ResultsSkeletal muscle kf determined by conventional approach and approach were the same 0.31 ± 0.02 s-1 and 0.30 ± 0.04 s-1 demonstrating the validity of the technique. Results are reported as mean ± SD. Myocardial CK reaction rate constant was 0.29 ± 0.05 s-1, consistent with previously reported studies.Conclusion method enables acquisition of 31P saturation transfer MRS under partially relaxed conditions and enables 2D-CSI of kf in myocardium. This work enables applications for in vivo CSI imaging of energetics in heart and other organs in clinically relevant acquisition time.

Phenylglyoxal inhibition of the mitochondrial F1FO-ATPase activated by Mg2+ or by Ca2+ provides clues on the mitochondrial permeability transition pore

Phenylglyoxal (PGO), known to cause post-translational modifications of Arg residues, was used to highlight the role of arginine residues of the F1FO-ATPase, which may be crucial to yield the mitochondrial permeability transition pore (mPTP). In swine heart mitochondria PGO inhibits ATP hydrolysis by the F1FO-ATPase either sustained by the natural cofactor Mg2+ or by Ca2+ by a similar uncompetitive inhibition mechanism, namely the tertiary complex (ESI) only forms when the ATP substrate is already bound to the enzyme, and with similar strength, as shown by the similar K'i values (0.82 ± 0.07 mM in presence of Mg2+ and 0.64 ± 0.05 mM in the presence of Ca2+). Multiple inhibitor analysis indicates that features of the F1 catalytic sites and/or the FO proton binding sites are apparently unaffected by PGO. However, PGO and F1 or FO inhibitors can bind the enzyme combine simultaneously. However they mutually hinder to bind the Mg2+-activated F1FO-ATPase, whereas they do not mutually exclude to bind the Ca2+-activated F1FO-ATPase. The putative formation of PGO-arginine adducts, and the consequent spatial rearrangement in the enzyme structure, inhibits the F1FO-ATPase activity but, as shown by the calcium retention capacity evaluation in intact mitochondria, apparently favours the mPTP formation.

High Frame Rate Ultrasound for Electromechanical Wave Imaging to Differentiate Endocardial From Epicardial Myocardial Activation

Differentiation between epicardial and endocardial ventricular activation remains a challenge despite the latest technologies available. The aim of the present study was to develop a new tool method, based on electromechanical wave imaging (EWI), to improve arrhythmogenic substrate activation analysis. Experiments were conducted on left ventricles (LVs) of four isolated working mode swine hearts. The protocol aimed at demonstrating that different patterns of mechanical activation could be observed whether the ventricle was in sinus rhythm, paced from the epicardium or from the endocardium. A total of 72 EWI acquisitions were recorded on the anterior, lateral and posterior segments of the LV. A total of 54 loop records were blindly assigned to two readers. EWI sequences interpretations were correct in 89% of cases. The overall agreement rate between the two readers was 83%. When in a paced ventricle, the origin of the wave front was focal and originated from the endocardium or the epicardium. In sinus rhythm, wave front was global and activated within the entire endocardium toward the epicardium at a speed of 1.7 ± 0.28 m·s−1. Wave front speeds were respectively measured when the endocardium or the epicardium were paced at a speed of 1.1 ± 0.35 m·s−1 versus 1.3 ± 0.34 m·s−1 (p = NS). EWI activation mapping allows activation localization within the LV wall and calculation of the wave front propagation speed through the muscle. In the future, this technology could help localize activation within the LV thickness during complex ablation procedures.

Transapical septal myectomy in the beating heart via a minimally invasive approach: a feasibility study in swine

The aim of this study was to establish an original transapical septal myectomy procedure that can be performed in the beating heart via a minimally invasive approach for the treatment of hypertrophic obstructive cardiomyopathy. We designed an original intracardiac septum resection device to conduct off-pump septal myectomy in swine. A subxiphoid minithoracotomy was performed to access the apex of the heart. This resection device was inserted into the left ventricular outflow tract of the heart via the apex. The basal anteroseptal myocardium beneath the right aortic cusp was identified using a combination of transoesophageal and transthoracic echocardiography and then resected and collected by the device. Six consecutive operations were successfully and accurately performed using the custom-made device under echocardiographic guidance. All pigs survived and appeared to be normal until planned euthanasia 1 week after operation. A 300-700 mg portion of the septal myocardium was resected from the normal swine heart. Echocardiography and electrocardiogram revealed no abnormalities after resection. One exception was the fifth pig, in which mild annular regurgitation of the aortic valve occurred after repetitive resection. Postmortem necropsy demonstrated that all resections were correctly located at the basal anteroseptal septum beneath the right aortic cusp. Our study provides the first proof-of-concept evidence for a novel beating heart transapical septal myectomy procedure, which showed promising translational potential for the treatment of hypertrophic obstructive cardiomyopathy. This procedure would probably reduce operative risks and improve outcomes and reduce the demanding expertise required to perform conventional surgical myectomy.

P2862Complementary use of contact force and local catheter impedance during RF ablation reduces ablation time in an in vivo swine model

Abstract Catheter-tissue coupling is crucial for effective delivery of radiofrequency (RF) energy during catheter ablation. Force sensing catheters provide a metric of mechanical tissue contact and catheter stability, while local impedance has been shown to provide sensitive information on real-time tissue heating. The complementary use of force and local impedance during RF ablation procedures could provide an advantage over the use of one metric alone. This study evaluates a prototype ablation catheter that measures both contact force (CF) using inductive sensors and local catheter impedance (LI) using only catheter electrodes. The complementary nature was assessed with discrete lesions in vitro and an intercaval line in vivo. A force-sensing catheter with LI was evaluated in explanted swine hearts (n=14) in an in vivo swine model (n=9, 50–70kg) using investigational electroanatomical mapping software. In vitro, discrete lesions were created in ventricular tissue at a range of forces (0–40g) controlled externally. RF energy was applied at a range of powers (20W, 30W, and 40W), durations (10s-60s), and catheter orientations (0°, 45°, and 90°). Lesions were stained with TTC and measured. LI drop relative to baseline during RF in the bench studies was used to inform the in vivo study. In a separate subset of animals in vivo, an intercaval line was created in three experimental groups: LI blinded, 20Ω ΔLI, and 30Ω ΔLI. CF was maintained between 15 and 25g in all groups. All ablations were performed with a power of 30W. In the LI blinded group, all lesions were delivered for 30s. In the 20Ω ΔLI group, the investigator ablated until a 20Ω drop or 30 seconds was achieved. Likewise, in the 30Ω ΔLI, the investigator ablated until a 30Ω drop or 30 seconds was achieved. In vitro, 137 discrete ventricular lesions were created. LI drop during ablation correlated strongly with lesion depth using a monoexponential fit (R=0.84) while force time integral (FTI) did not correlate as strongly (R=0.56). In the intercaval LI blinded group, starting LI ranged from 126–163Ω with a median of 138Ω. LI drops ranged from 13Ω-44Ω, with a median of 26Ω. In the 20Ω ΔLI group, starting LI ranged from 137–211Ω with a median of 161Ω and LI drop ranged from 7Ω-35Ω, with a median of 22Ω. In the 30Ω ΔLI group, starting LI ranged from 130–256Ω with a median of 171Ω and LI drop ranged from 20Ω-52Ω, with a median of 31Ω. Notably, RF time for the LI blinded group was 13±0.1 minutes while RF time in the 20Ω ΔLI group was 6.4±1.9 minutes and 7.5±0.7 minutes in the 30Ω ΔLI group. A catheter incorporating CF-sensing and LI capabilities provides a powerful tool for RF ablation. Bench studies demonstrate a strong correlation between LI drop and lesion dimensions, which guided the use of LI in vivo. In vivo, the confirmation of stable mechanical contact and viewing of real-time LI drops enabled a significant reduction in RF time while creating a continuous intercaval line. Acknowledgement/Funding This study was funded by Boston Scientific.

TCT-444 Left Ventricular Thinning and Distension to Mimic Heart Failure and Functional Mitral Regurgitation in Swine Hearts: A Platform to Test New Transcatheter Mitral and Heart Failure Devices

The need for clinically relevant experimental platforms of functional mitral regurgitation (FMR) are necessary to test new transcatheter mitral valve devices. Isolated mitral valve models of FMR have been reported previously, but they lack a left ventricle (LV). This study reports a novel model of

A High-Resolution Triaxial Catheter Tip Force Sensor With Miniature Flexure and Suspended Optical Fibers

This article reports a miniature, high-resolution fiber Bragg grating (FBG)-based triaxial force sensor to detect the catheter tip–tissue interaction forces. This sensor counts on a delicate three-dimensional-printed flexure comprising a cylinder with an inner elliptical cavity for detecting lateral forces and a hybrid elastomer to enhance axial elasticity for improving z -directional force sensitivity. Four suspended optical fibers inscribed with FBG each are deployed inside the flexure. Such configurations are designed to maximize the decoupling among three force components, achieve temperature compensation, and raise the sensor's robustness under biofluid-filled environments. The sensor characterization results indicate a high resolution of 0.52 and 0.64 mN for both lateral forces within –0.8 to 0.8 N and 0.63 mN for axial direction force within 0–0.8 N. Validation with dynamic loadings along different azimuth angles shows that the sensor can provide a high-accuracy measurement of three force components with an rms error of less than 3.00%. Temperature-induced errors for force detection are considerably alleviated, showing less than 6.5% in the range of 25 °C–50 °C. Ex vivo experiments on a swine heart further validate the performances of the designed sensor.

In Vitro and Ex Vivo Hemodynamic Testing of an Innovative Occluder for Paravalvular Leak After Transcather Aortic Valve Implantation.

This study aims at achieving a proof-of-concept for a novel device designed to occlude the orifices that may form between transcatheter valves and host tissues after TAVI. The device effect on the performance of a SAPIEN XT with a paravalvular gap was assessed into an in vitro and ex vivo pulse duplicator. The in vitro tests were performed complying with the standard international regulations, measuring the trasvalvular pressure and regurgitant volumes with and without the paravalvular gap, and with the occluder correctly positioned into the gap. In the second series of tests, the leakage reduction due to the presence of the occluder was assessed for the same setup, into a beating swine heart. The occluder implantation decreased the regurgitant fraction of about 50% for the in vitro assessment and 75% for the ex vivo test, under rest operating conditions. These results suggest that suitably designed occluders can lead to important benefit in the PVL treatment.