Catheter-tissue contact optimizes pulsed electric field ablation with a large area focal catheter.

INTRODUCTION: Pulsed electric field (PEF) ablation relies on the intersection of a critical voltage gradient with tissue to cause cell death. Field-based lesion formation with PEF technologies may still depend on catheter-tissue contact (CTC). The purpose of this study was to assess the impact of CTC on PEF lesion formation with an investigational large area focal (LAF) catheter in a preclinical model. METHODS: PEF ablation via a 10-spline LAF catheter was used to create discrete right ventricle (RV) lesions and atrial lesion sets in 10 swine (eight acute, two chronic). Local impedance (LI) was used to assess CTC. Lesions were assigned to three cohorts using LI above baseline: no tissue contact (NTC: ≤∆10 Ω, close proximity to tissue), low tissue contact (LTC: ∆11-29 Ω), and high tissue contact (HTC: ≥∆30 Ω). Acute animals were infused with triphenyl tetrazolium chloride (TTC) and killed ≥2 h post-treatment. Chronic animals were remapped 30 days post-index procedure and stained with infused TTC. RESULTS: Mean (± SD) RV treatment sizes between LTC (n = 14) and HTC (n = 17) lesions were not significantly different (depth: 5.65 ± 1.96 vs. 5.68 ± 2.05 mm, p = .999; width: 15.68 ± 5.22 vs. 16.98 ± 4.45 mm, p = .737), while mean treatment size for NTC lesions (n = 6) was significantly smaller (1.67 ± 1.16 mm depth, 5.97 ± 4.48 mm width, p < .05). For atrial lesion sets, acute and chronic conduction block were achieved with both LTC (N = 7) and HTC (N = 6), and NTC resulted in gaps. CONCLUSIONS: PEF ablation with a specialized LAF catheter in a swine model is dependent on CTC. LI as an indicator of CTC may aid in the creation of consistent transmural lesions in PEF ablation.

Effects of Contact Force on Lesion Size During Pulsed Field Catheter Ablation: Histochemical Characterization of Ventricular Lesion Boundaries.

BACKGROUND: Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model. METHODS: A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining. RESULTS: Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.

Local Impedance Drop Predicts Durable Conduction Block in Patients With Paroxysmal Atrial Fibrillation.

OBJECTIVES: This analysis was performed to evaluate the transition of local impedance (LI) drop during pulmonary vein isolation (PVI) to durable block and mature lesion formation based on 3-month mapping procedures. BACKGROUND: A radiofrequency catheter measuring LI has been shown to be effective for performing PVI in patients with paroxysmal atrial fibrillation. Previous analysis has demonstrated LI drop to be predictive of pulmonary vein segment conduction block during an atrial fibrillation ablation procedure. METHODS: Fifty-eight patients who had undergone LI-blinded de novo PVI returned for a 3-month mapping procedure. PVI ablation circles were divided into 16 anatomic segments for classification (durable block or gap), and the median LI drop within segments with an interlesion distance of ≤6 mm was compared. A total of 51 data sets met the criteria for segmental analysis of LI performance. RESULTS: At the 3-month procedure, PV connection was confirmed in at least 1 PV segment in 35 of the included patients. LI drop outperformed generator impedance drop as a predictor of durable conduction block (area under the receiver-operating characteristic curve: 0.79 vs 0.68; P = 0.003). Optimal LI drops were identified by left atrial region (anterior/superior: 16.9 Ω [sensitivity: 69.1%; specificity: 85.0%; positive predictive value for durable conduction block: 97.7%]; posterior/inferior:14.2 Ω [sensitivity: 73.8%; specificity: 78.3%; positive predictive value: 96.9%]). Starting LI before radiofrequency (RF) application was significantly different among healthy, gap, and mature scar tissue and was also a contributing factor to achieving an optimal LI drop (85.2% of RF applications with a starting LI of ≥110 Ω achieved the optimal regional drop or greater). CONCLUSIONS: LI drop is predictive of durable PV segment isolation. Preablation starting LI is associated with the magnitude of LI drop. These findings suggest that a regional approach to RF ablation guided by LI combined with careful interlesion distance control may be beneficial in patients with paroxysmal atrial fibrillation (Electrical Coupling Information From the Rhythmia HDx System and DirectSense Technology in Subjects With Paroxysmal Atrial Fibrillation [LOCALIZE]; NCT03232645).

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

Local catheter impedance drop during pulmonary vein isolation predicts acute conduction block in patients with paroxysmal atrial fibrillation: initial results of the LOCALIZE clinical trial.

AIMS: Radiofrequency ablation creates irreversible cardiac damage through resistive heating and this temperature change results in a generator impedance drop. Evaluation of a novel local impedance (LI) technology measured exclusively at the tip of the ablation catheter found that larger LI drops were indicative of more effective lesion formation. We aimed to evaluate whether LI drop is associated with conduction block in patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI). METHODS AND RESULTS: Sixty patients underwent LI-blinded de novo PVI using a point-by-point ablation workflow. Pulmonary vein rings were divided into 16 anatomical segments. After a 20-min waiting period, gaps were identified on electroanatomic maps. Median LI drop within segments with inter-lesion distance ≤6 mm was calculated offline. The diagnostic accuracy of LI drop for predicting segment block was assessed using receiver operating characteristic analysis. For segments with inter-lesion distance ≤6 mm, acutely blocked segments had a significantly larger LI drop [19.8 (14.1-27.1) Ω] compared with segments with gaps [10.6 (7.8-14.7) Ω, P < 0.001). In view of left atrial wall thickness differences, the association between LI drop and block was further evaluated for anterior/roof and posterior/inferior segments. The optimal LI cut-off value for anterior/roof segments was 16.1 Ω (positive predictive value for block: 96.3%) and for posterior/inferior segments was 12.3 Ω (positive predictive value for block: 98.1%) where inter-lesion distances were ≤6 mm. CONCLUSION: The magnitude of LI drop was predictive of acute PVI segment conduction block in patients with paroxysmal AF. The thinner posterior wall required smaller LI drops for block compared with the thicker anterior wall.

Combined local impedance and contact force for radiofrequency ablation assessment.

BACKGROUND: The combination of contact force (CF) and local impedance (LI) may improve tissue characterization and lesion prediction during radiofrequency (RF) ablation. OBJECTIVE: The purpose of this study was to evaluate the utility of LI combined with CF in assessing RF ablation efficacy. METHODS: An LI catheter with CF sensing was evaluated in swine (n = 11) and in vitro (n = 14). The relationship between LI and CF in different tissue types was evaluated in vivo. Discrete lesions were created in vitro and in vivo at a range of forces, powers, and durations. Finally, an intercaval line was created in 3 groups at 30 W: 30s, Δ20Ω, and Δ30Ω. In the Δ20Ω and Δ30Ω groups, the user ablated until a 20 or 30 Ω LI drop. In the 30s group, the user was blinded to LI. RESULTS: In vivo, distinction in LI was found between the blood pool and the myocardium (blood pool: 122 ± 7.02 Ω; perpendicular contact: 220 ± 29 Ω; parallel contact: 207 ± 31 Ω). LI drop correlated with lesion depth both in vitro (R = 0.84) and in vivo (R = 0.79), informing sufficient lesion creation (LI drop >20 Ω) and warning of excessive heating (LI drop >65 Ω). When creating an intercaval line, the total RF time was significantly reduced when using LI guidance (6.4 ± 2 minutes in Δ20Ω and 8.1 ± 1 minutes in Δ30Ω) compared with a standard 30-second workflow (18 ± 7 minutes). Acute conduction block was achieved in all Δ30Ω and 30s lines. CONCLUSION: The addition of LI to CF provides feedback on both electrical and mechanical loads. This provides information on tissue type and catheter-tissue coupling; provides feedback on whether volumetric tissue heating is inadequate, sufficient, or excessive; and reduces ablation time.

Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation: Results From the STARLIGHT Study.

BACKGROUND: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping. METHODS: Patients with persistent atrial fibrillation (n=14; mean age, 61±8 years; ejection fraction, 59±10%) underwent simultaneous biatrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase, and subsequent spatiotemporal mapping was performed to identify phase singularities (PSs). RESULTS: PSs were located in both atria, but we observed more PSs in the left atrium compared with the right atrium (779±302, 552±235; P=0.015). Although some PSs of duration sufficient to complete >1 rotation were detected, the maximum PS duration was only 1150 ms, and the vast majority (97%) of PSs persisted for too short a period to complete a full rotation. Although in selected patients there was evidence of PS local clustering, overall, PSs were distributed globally throughout both chambers with no clear anatomic predisposition. In a subset of patients (n=7), analysis was repeated using an alternative established atrial PS mapping technique, which confirmed our initial findings. CONCLUSIONS: No sustained rotors or localized drivers were detected, and instead, the mechanism of arrhythmia maintenance was consistent with the multiple wavelet hypothesis, with passive activation of short-lived rotational activity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01765075.

Novel Measure of Local Impedance Predicts Catheter-Tissue Contact and Lesion Formation.

BACKGROUND: Coupling between the ablation catheter and myocardium is critical to resistively heat tissue with radiofrequency ablation. The objective of this study was to evaluate whether a novel local impedance (LI) measurement on an ablation catheter identifies catheter-tissue coupling and is predictive of lesion formation. METHODS AND RESULTS: LI was studied in explanted hearts (n=10 swine) and in vivo (n=10; 50-70 kg swine) using an investigational electroanatomic mapping system that measures impedance from an ablation catheter with mini-electrodes incorporated in the distal electrode (Rhythmia and IntellaNav MiFi OI, Boston Scientific). Explanted tissue was placed in a warmed (37 °C) saline bath mounted on a scale, and LI was measured 15 mm away from tissue to 5 mm of catheter-tissue compression at multiple catheter angles. Lesions were created with 31 and 50 W for 5 to 45 seconds (n=90). During in vivo evaluation of LI, measurements of myocardium (n=90) and blood pool (n=30) were guided by intracardiac ultrasound while operators were blinded to LI data. Lesions were created with 31 and 50 W for 45 seconds in the ventricles (n=72). LI of myocardium (119.7 Ω) was significantly greater than that of blood pool (67.6 Ω; P<0.01). Models that incorporate LI drop (ΔLI) to predict lesion size had better performance than models that incorporate force-time integral (R2=0.75 versus R2=0.54) and generator impedance drop (R2=0.82 versus R2=0.58). Steam pops displayed a significantly higher starting LI and larger ΔLI compared with successful radiofrequency applications (P<0.01). CONCLUSIONS: LI recorded from miniature electrodes provides a valuable measure of catheter-tissue coupling, and ΔLI is predictive of lesion formation during radiofrequency ablation.

Practical Considerations of Mapping Persistent Atrial Fibrillation With Whole-Chamber Basket Catheters.

OBJECTIVES: This study sought to evaluate basket catheter deployment, catheter-tissue contact, and time-space stability of unipolar atrial electrograms (aEGMs) recorded in persistent atrial fibrillation (AF) patients. BACKGROUND: Panoramic mapping of human AF using multiple-electrode basket catheters may identify AF sources. Although clinical results using this technique are provocative, questions remain about its effectiveness. METHODS: Data were collected from patients (N = 25) undergoing catheter ablation for AF during the multicenter STARLIGHT (Signal Transfer of Atrial Fibrillation Data to Guide Human Treatment) trial (NCT01765075). Left and right aEGM signals were recorded using basket catheters during baseline AF, following ablation and during sinus rhythm. Data were analyzed for basket deployment, peak-to-peak voltage, and electrogram stability and organization. Electrogram stability and organization were evaluated via time-frequency analysis (TFA). RESULTS: Basket catheters displayed equatorial bunching when deployed in atria. Interspline spacing ranged from 1.7 to 64.0 mm in the right atrial and from 1.5 to 85.08 mm in the left atrial basket. Approximately one-third of mapping electrodes failed to demonstrate a median peak-to-peak voltage >2× the low-voltage threshold. Time-space stability and organization was observed in 13 of 22 (59.09%) right atrial and 10 of 22 (45.45%) left atrial baskets. CONCLUSIONS: Despite poor deployment and a large number of low-voltage electrodes, stability and organization was observed in about one-half of the mapped patients. Although this study suggests that basket catheters have limitations for patient-specific AF mapping, concordant activation occurs in some persistent AF patients, which may be amenable to high-density mapping techniques.

Electrophysiological changes correlated with temperature increases induced by high-intensity focused ultrasound ablation.

To gain better understanding of the detailed mechanisms of high-intensity focused ultrasound (HIFU) ablation for cardiac arrhythmias, we investigated how the cellular electrophysiological (EP) changes were correlated with temperature increases and thermal dose (cumulative equivalent minutes [CEM43]) during HIFU application using Langendorff-perfused rabbit hearts. Employing voltage-sensitive dye di-4-ANEPPS, we measured the EP and temperature during HIFU using simultaneous optical mapping and infrared imaging. Both action potential amplitude (APA) and action potential duration at 50% repolarization (APD50) decreased with temperature increases, and APD50 was more thermally sensitive than APA. EP and tissue changes were irreversible when HIFU-induced temperature increased above 52.3 ± 1.4°C and log10(CEM43) above 2.16 ± 0.51 (n = 5), but were reversible when temperature was below 50.1 ± 0.8°C and log10(CEM43) below -0.9 ± 0.3 (n = 9). EP and temperature/thermal dose changes were spatially correlated with HIFU-induced tissue necrosis surrounded by a transition zone.

Nanoscale three-dimensional imaging of the human myocyte.

The ventricular human myocyte is spatially organized for optimal ATP and Ca(2+) delivery to sarcomeric myosin and ionic pumps during every excitation-contraction cycle. Comprehension of three-dimensional geometry of the tightly packed ultrastructure has been derived from discontinuous two-dimensional images, but has never been precisely reconstructed or analyzed in human myocardium. Using a focused ion beam scanning electron microscope, we created nanoscale resolution serial images to quantify the three-dimensional ultrastructure of a human left ventricular myocyte. Transverse tubules (t-tubule), lipid droplets, A-bands, and mitochondria occupy 1.8, 1.9, 10.8, and 27.9% of the myocyte volume, respectively. The complex t-tubule system has a small tortuosity (1.04±0.01), and is composed of long transverse segments with diameters of 317±24nm and short branches. Our data indicates that lipid droplets located well beneath the sarcolemma are proximal to t-tubules, where 59% (13 of 22) of lipid droplet centroids are within 0.50µm of a t-tubule. This spatial association could have an important implication in the development and treatment of heart failure because it connects two independently known pathophysiological alterations, a substrate switch from fatty acids to glucose and t-tubular derangement.

3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium.

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

A fully implantable pacemaker for the mouse: from battery to wireless power.

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.

3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique.

This paper presents a two-frequency binary phase-shifting technique to measure three-dimensional (3D) absolute shape of beating rabbit hearts. Due to the low contrast of the cardiac surface, the projector and the camera must remain focused, which poses challenges for any existing binary method where the measurement accuracy is low. To conquer this challenge, this paper proposes to utilize the optimal pulse width modulation (OPWM) technique to generate high-frequency fringe patterns, and the error-diffusion dithering technique to produce low-frequency fringe patterns. Furthermore, this paper will show that fringe patterns produced with blue light provide the best quality measurements compared to fringe patterns generated with red or green light; and the minimum data acquisition speed for high quality measurements is around 800 Hz for a rabbit heart beating at 180 beats per minute.

Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes.

Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists regarding the optimum methods. The specific methods chosen to process optical mapping data are important because inappropriate data processing can affect the content of the data and thus alter the conclusions of the studies. Details of the different steps in processing optical imaging data, including image segmentation, spatial filtering, temporal filtering, and baseline drift removal, are provided in this review. We also provide descriptions of the common analyses performed on data obtained from cardiac optical imaging, including activation mapping, action potential duration mapping, repolarization mapping, conduction velocity measurements, and optical action potential upstroke analysis. Optical mapping is often used to study complex arrhythmias, and we also discuss dominant frequency analysis and phase mapping techniques used for the analysis of cardiac fibrillation.

Mapping cardiac surface mechanics with structured light imaging.

Cardiovascular disease often manifests as a combination of pathological electrical and structural heart remodeling. The relationship between mechanics and electrophysiology is crucial to our understanding of mechanisms of cardiac arrhythmias and the treatment of cardiac disease. While several technologies exist for describing whole heart electrophysiology, studies of cardiac mechanics are often limited to rhythmic patterns or small sections of tissue. Here, we present a comprehensive system based on ultrafast three-dimensional (3-D) structured light imaging to map surface dynamics of whole heart cardiac motion. Additionally, we introduce a novel nonrigid motion-tracking algorithm based on an isometry-maximizing optimization framework that forms correspondences between consecutive 3-D frames without the use of any fiducial markers. By combining our 3-D imaging system with nonrigid surface registration, we are able to measure cardiac surface mechanics at unprecedented spatial and temporal resolution. In conclusion, we demonstrate accurate cardiac deformation at over 200,000 surface points of a rabbit heart recorded at 200 frames/s and validate our results on highly contrasting heart motions during normal sinus rhythm, ventricular pacing, and ventricular fibrillation.

Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue.

BACKGROUND: High intensity focused ultrasound (HIFU) has been introduced for treatment of cardiac arrhythmias because it offers the ability to create rapid tissue modification in confined volumes without directly contacting the myocardium. In spite of the benefits of HIFU, a number of limitations have been reported, which hindered its clinical adoption. METHODS AND RESULTS: In this study, we used a multimodal approach to evaluate thermal and nonthermal effects of HIFU in cardiac ablation. We designed a computer controlled system capable of simultaneous fluorescence mapping and HIFU ablation. Using this system, linear lesions were created in isolated rabbit atria (n=6), and point lesions were created in the ventricles of whole-heart (n=6) preparations by applying HIFU at clinical doses (4-16 W). Additionally, we evaluate the gap size in ablation lines necessary for conduction in atrial preparations (n=4). The voltage sensitive dye di-4-ANEPPS was used to assess functional damage produced by HIFU. Optical coherence tomography and general histology were used to evaluate lesion extent. Conduction block was achieved in 1 (17%) of 6 atrial preparations with a single ablation line. Following 10 minutes of rest, 0 (0%) of 6 atrial preparations demonstrated sustained conduction block from a single ablation line. Tissue displacement of 1 to 3 mm was observed during HIFU application due to acoustic radiation force along the lesion line. Additionally, excessive acoustic pressure and high temperature from HIFU generated cavitation, causing macroscopic tissue damage. A minimum gap size of 1.5 mm was found to conduct electric activity. CONCLUSIONS: This study identified 3 potential mechanisms responsible for the failure of HIFU ablation in cardiac tissues. Both acoustic radiation force and acoustic cavitation, in conjunction with inconsistent thermal deposition, can increase the risk of lesion discontinuity and result in gap sizes that promote ablation failure.

Structured light imaging of epicardial mechanics.

There is a need for accurate measurements of mechanical strain and motion of the heart both in vitro and in vivo. We have developed a new structured-light imaging system capable of epicardial shape measurement at 333 fps at a resolution of 768 × 768 pixels. Here we present proof-of-concept data from our system applied to a beating rabbit heart in vitro to measure epicardial mechanics. This method will allow high resolution mapping of epicardial strain and virtual immobilization of the heart for removal of motion artifacts from epicardial recordings with fluorescence dyes. This will allow mapping of transmembrane potential and calcium transients in a beating heart, including in vivo.

Connexin 43 expression delineates two discrete pathways in the human atrioventricular junction.

Gap junction expression has been studied in the atrioventricular junction (AVJ) of many species, however, their distribution in the human AVJ is unknown. The AVJ expression of the gap junction protein connexin 43 (Cx43) is species dependent; therefore we investigated its distribution in the human AVJ. Using Masson trichrome histology, we reconstructed the AVJ of three normal human hearts and one with dilated cardiomyopathy in three dimensions. Cx43 was immunolabeled with vimentin and alpha-actinin to determine the cellular origin of Cx43 and was quantified in the following structures: interatrial septum (IAS), His bundle, compact node (CN), lower nodal bundle (LNB), leftward and rightward nodal extensions (LE and RE), and inferior, endocardial, and left-sided transitional cells. Histology revealed two nodal extensions in three of four hearts. Cx43 was found in the myocytes, but not fibroblasts, of the AVJ. LE and CN Cx43 was lower than the IAS (P < 0.05) and the RE, LNB, and His all expressed Cx43 similarly, with approximately half of IAS expression (RE: 44 +/- 36%; LNB: 50 +/- 26%; His: 48 +/- 12%, P = NS compared with IAS). Cx43 levels in transitional cells were similar to the IAS (P = not significant). Cx43 was found in myocytes of the human AVJ, and its expression pattern delineates two separate continuous structures: one consists of the LE and CN with little Cx43, and the other consists of the His, LNB, and RE expressing approximately half the Cx43 of the IAS. The differential Cx43 expression may provide each structure with unique conduction properties, contributing to arrhythmias arising from the AVJ.