Improved Ablation Efficiency in PVI Guided by Contact Force and Local Impedance: Chronic Canine Model.

Background: The purpose of this study was to assess the effect local impedance (LI) has on an ablation workflow when combined with a contact force (CF) ablation catheter. Methods: Left pulmonary vein isolation was performed in an in vivo canine model (N = 8) using a nominal (30 W) or an elevated (50 W) power strategy with a CF catheter. The catheter was enabled to measure LI prior to and during ablation. LI was visible for only one of the vein isolations. Results: Chronic block was achieved in all animals when assessed 30 ± 5 days post-ablation procedure with a median LI drop during RF ranging from 23.0 to 34.0 Ω. In both power cohorts, the median radiofrequency (RF) duration decreased if LI was visible to the operator (30 W only CF: 17.0 s; 30 W CF + LI: 14.0 s, p = 0.009; 50 W only CF: 6.0 s; 50 W CF + LI: 4.0 s, p = 0.019). An inverse relationship between the LI prior to RF delivery and the RF duration required to achieve an effective lesion was observed. There was no correlation between the magnitude of the applied force and the drop in LI, once at least 5 g was achieved. Conclusions: An elevated power strategy with the context of CF and LI led to the most efficient titration of successful RF energy delivery. The combination of feedback allows for customization of the ablation strategy based on local tissue variation rather than a uniform approach that could potentially lead to overtreatment. Higher LI drops were more readily achievable when an elevated power strategy was utilized, especially in conditions where the catheter was coupled against tissue with low resistivity. Clinical study is warranted to determine if there is an additive safety benefit to visualizing the dynamics of the tissue response to RF energy with LI when an elevated power strategy is used.

Ultrathin Injectable Sensors of Temperature, Thermal Conductivity, and Heat Capacity for Cardiac Ablation Monitoring.

Knowledge of the distributions of temperature in cardiac tissue during and after ablation is important in advancing a basic understanding of this process, and for improving its efficacy in treating arrhythmias. Technologies that enable real-time temperature detection and thermal characterization in the transmural direction can help to predict the depths and sizes of lesion that form. Herein, materials and designs for an injectable device platform that supports precision sensors of temperature and thermal transport properties distributed along the length of an ultrathin and flexible needle-type polymer substrate are introduced. The resulting system can insert into the myocardial tissue, in a minimally invasive manner, to monitor both radiofrequency ablation and cryoablation, in a manner that has no measurable effects on the natural mechanical motions of the heart. The measurement results exhibit excellent agreement with thermal simulations, thereby providing improved insights into lesion transmurality.

Imaging of Ventricular Fibrillation and Defibrillation: The Virtual Electrode Hypothesis.

Ventricular fibrillation is the major underlying cause of sudden cardiac death. Understanding the complex activation patterns that give rise to ventricular fibrillation requires high resolution mapping of localized activation. The use of multi-electrode mapping unraveled re-entrant activation patterns that underlie ventricular fibrillation. However, optical mapping contributed critically to understanding the mechanism of defibrillation, where multi-electrode recordings could not measure activation patterns during and immediately after a shock. In addition, optical mapping visualizes the virtual electrodes that are generated during stimulation and defibrillation pulses, which contributed to the formulation of the virtual electrode hypothesis. The generation of virtual electrode induced phase singularities during defibrillation is arrhythmogenic and may lead to the induction of fibrillation subsequent to defibrillation. Defibrillating with low energy may circumvent this problem. Therefore, the current challenge is to use the knowledge provided by optical mapping to develop a low energy approach of defibrillation, which may lead to more successful defibrillation.

Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy.

Advanced materials and fractal design concepts form the basis of a 3D conformal electronic platform with unique capabilities in cardiac electrotherapies. Fractal geometries, advanced electrode materials, and thin, elastomeric membranes yield a class of device capable of integration with the entire 3D surface of the heart, with unique operational capabilities in low power defibrillation. Co-integrated collections of sensors allow simultaneous monitoring of physiological responses. Animal experiments on Langendorff-perfused rabbit hearts demonstrate the key features of these systems.

Quantification of the transmural dynamics of atrial fibrillation by simultaneous endocardial and epicardial optical mapping in an acute sheep model.

BACKGROUND: Therapy strategies for atrial fibrillation based on electric characterization are becoming viable personalized medicine approaches to treat a notoriously difficult disease. In light of these approaches that rely on high-density surface mapping, this study aims to evaluate the presence of 3-dimensional electric substrate variations within the transmural wall during acute episodes of atrial fibrillation. METHODS AND RESULTS: Optical signals were simultaneously acquired from the epicardial and endocardial tissue during acute fibrillation in ovine isolated left atria. Dominant frequency, regularity index, propagation angles, and phase dynamics were assessed and correlated across imaging planes to gauge the synchrony of the activation patterns compared with paced rhythms. Static frequency parameters were well correlated spatially between the endocardium and the epicardium (dominant frequency, 0.79 ± 0.06 and regularity index, 0.93 ± 0.009). However, dynamic tracking of propagation vectors and phase singularity trajectories revealed discordant activity across the transmural wall. The absolute value of the difference in the number, spatial stability, and temporal stability of phase singularities between the epicardial and the endocardial planes was significantly >0 with a median difference of 1.0, 9.27%, and 19.75%, respectively. The number of wavefronts with respect to time was significantly less correlated and the difference in propagation angle was significantly larger in fibrillation compared with paced rhythms. CONCLUSIONS: Atrial fibrillation substrates are dynamic 3-dimensional structures with a range of discordance between the epicardial and the endocardial tissue. The results of this study suggest that transmural propagation may play a role in atrial fibrillation maintenance mechanisms.

Patient-specific flexible and stretchable devices for cardiac diagnostics and therapy.

Advances in material science techniques and pioneering circuit designs have led to the development of electronic membranes that can form intimate contacts with biological tissues. In this review, we present the range of geometries, sensors, and actuators available for custom configurations of electronic membranes in cardiac applications. Additionally, we highlight the desirable mechanics achieved by such devices that allow the circuits and substrates to deform with the beating heart. These devices unlock opportunities to collect continuous data on the electrical, metabolic, and mechanical state of the heart as well as a platform on which to develop high definition therapeutics.

Mitochondrial depolarization and electrophysiological changes during ischemia in the rabbit and human heart.

Instability of the inner mitochondrial membrane potential (ΔΨm) has been implicated in electrical dysfunction, including arrhythmogenesis during ischemia-reperfusion. Monitoring ΔΨm has led to conflicting results, where depolarization has been reported as sporadic and as a propagating wave. The present study was designed to resolve the aforementioned difference and determine the unknown relationship between ΔΨm and electrophysiology. We developed a novel imaging modality for simultaneous optical mapping of ΔΨm and transmembrane potential (Vm). Optical mapping was performed using potentiometric dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts. Our data showed that during ischemia, ΔΨm depolarization is sporadic and changes asynchronously with electrophysiological changes. Spatially, ΔΨm depolarization was associated with action potential duration shortening but not conduction slowing. Analysis of focal activity indicated that ΔΨm is not different within the myocardium where the focus originates compared with normal ventricular tissue. Overall, our data suggest that during ischemia, mitochondria maintain their function at the expense of sarcolemmal electrophysiology, but ΔΨm depolarization does not have a direct association to ischemia-induced arrhythmias.

A shocking past: a walk through generations of defibrillation development.

Defibrillation is one of the most successful and widely recognized applications of electrotherapy. Yet the historical road to its first successful application in a patient and the innovative adaptation to an implantable device is marred with unexpected turns, political and personal setbacks, and public and scientific condemnation at each new idea. Driven by dedicated scientists and ever-advancing creative applications of new technologies, from electrocardiography to high density mapping and computational simulations, the field of defibrillation persevered and continued to evolve to the life-saving tool it is today. In addition to critical technological advances, the history of defibrillation is also marked by the plasticity of the theory of defibrillation. The advancing theories of success have propelled the campaign for reducing the defibrillation energy requirement, instilling hope in the development of a painless and harmless electrical defibrillation strategy.

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.

Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock.

OBJECTIVES: The goal of this study was to develop a low-energy, implantable device-based multistage electrotherapy (MSE) to terminate atrial fibrillation (AF). BACKGROUND: Previous attempts to perform cardioversion of AF by using an implantable device were limited by the pain caused by use of a high-energy single biphasic shock (BPS). METHODS: Transvenous leads were implanted into the right atrium (RA), coronary sinus, and left pulmonary artery of 14 dogs. Self-sustaining AF was induced by 6 ± 2 weeks of high-rate RA pacing. Atrial defibrillation thresholds of standard versus experimental electrotherapies were measured in vivo and studied by using optical imaging in vitro. RESULTS: The mean AF cycle length (CL) in vivo was 112 ± 21 ms (534 beats/min). The impedances of the RA-left pulmonary artery and RA-coronary sinus shock vectors were similar (121 ± 11 Ω vs. 126 ± 9 Ω; p = 0.27). BPS required 1.48 ± 0.91 J (165 ± 34 V) to terminate AF. In contrast, MSE terminated AF with significantly less energy (0.16 ± 0.16 J; p < 0.001) and significantly lower peak voltage (31.1 ± 19.3 V; p < 0.001). In vitro optical imaging studies found that AF was maintained by localized foci originating from pulmonary vein-left atrium interfaces. MSE Stage 1 shocks temporarily disrupted localized foci; MSE Stage 2 entrainment shocks continued to silence the localized foci driving AF; and MSE Stage 3 pacing stimuli enabled consistent RA-left atrium activation until sinus rhythm was restored. CONCLUSIONS: Low-energy MSE significantly reduced the atrial defibrillation thresholds compared with BPS in a canine model of AF. MSE may enable painless, device-based AF therapy.

Three-dimensional printing physiology laboratory technology.

Since its inception in 19th-century Germany, the physiology laboratory has been a complex and expensive research enterprise involving experts in various fields of science and engineering. Physiology research has been critically dependent on cutting-edge technological support of mechanical, electrical, optical, and more recently computer engineers. Evolution of modern experimental equipment is constrained by lack of direct communication between the physiological community and industry producing this equipment. Fortunately, recent advances in open source technologies, including three-dimensional printing, open source hardware and software, present an exciting opportunity to bring the design and development of research instrumentation to the end user, i.e., life scientists. Here we provide an overview on how to develop customized, cost-effective experimental equipment for physiology laboratories.