63 research outputs found

    Nanosecond Stimulation and Defibrillation of Langendorff-Perfused Rabbit Hearts

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    The search for novel defibrillation methodologies focuses on minimizing deposition of energy to the heart, as this is an indicator for side effects including pain and tissue death. In this work, we investigate the effect of reducing the duration of the applied shocks from low milliseconds to the nanosecond range. 300 ns defibrillation was observed and confirmed to require lower energy than monophasic shocks by almost an order of magnitude with no tissue damage. Additionally, the safety factor, the ratio of median effective doses for electroporative damage and defibrillation, was similar for both durations. To predict how defibrillation shocks of any duration affect the heart, the stimulation strength-duration curve from 200 ns to 10 ms was determined. To investigate whether high frequency trains of nanosecond shocks (MHz compression) are capable of reducing the electric field and energy of defibrillation, they were compared with a single shock of the same duration. The average voltage for the pulse trains was slightly lower than for long shocks, but the energy almost doubled. Finally, to understand how shocks even shorter than 300 ns perform, we attempted to determine the defibrillation threshold of 60 ns shocks. Both the estimated electric field and energy were markedly higher than for 300 ns. We also investigated the stimulation threshold of 60 ns shocks followed by a negative phase of varying amplitude and showed that the negative phase reduces the ability of the shocks to stimulate. In conclusion, this work contributes to the understanding of how nanosecond shocks interact with cardiac tissues. It shows that 300 ns defibrillation is effective and similarly safe as 10 ms shocks, while requiring almost an order of magnitude less energy. The stimulation strength duration curve for cardiac tissue follows the same trend, with lower than expected thresholds for nanosecond shocks. However, low voltage MHz compressed nanosecond shocks are similarly effective as long shocks of the same duration, indicating that the greater efficacy of nanosecond defibrillation is linked to the effects of high voltage. Finally, investigations in 60 ns shocks show defibrillation and stimulation are possible, and that bipolar cancellation occurs in cardiac tissue

    High Resolution Multi-parametric Diagnostics and Therapy of Atrial Fibrillation: Chasing Arrhythmia Vulnerabilities in the Spatial Domain

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    After a century of research, atrial fibrillation (AF) remains a challenging disease to study and exceptionally resilient to treatment. Unfortunately, AF is becoming a massive burden on the health care system with an increasing population of susceptible elderly patients and expensive unreliable treatment options. Pharmacological therapies continue to be disappointingly ineffective or are hampered by side effects due to the ubiquitous nature of ion channel targets throughout the body. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, ablation procedures can be complex, leading to varying levels of recurrence, and have a number of serious risks. The high recurrence rate could be due to the difficulty of accurately predicting where to draw the ablation lines in order to target the pathophysiology that initiates and maintains the arrhythmia or an inability to distinguish sub-populations of patients who would respond well to such treatments. There are electrical cardioversion options but there is not a practical implanted deployment of this strategy. Under the current bioelectric therapy paradigm there is a trade-off between efficacy and the pain and risk of myocardial damage, all of which are positively correlated with shock strength. Contrary to ventricular fibrillation, pain becomes a significant concern for electrical defibrillation of AF due to the fact that a patient is conscious when experiencing the arrhythmia. Limiting the risk of myocardial injury is key for both forms of fibrillation. In this project we aim to address the limitations of current electrotherapy by diverging from traditional single shock protocols. We seek to further clarify the dynamics of arrhythmia drivers in space and to target therapy in both the temporal and spatial domain; ultimately culminating in the design of physiologically guided applied energy protocols. In an effort to provide further characterization of the organization of AF, we used transillumination optical mapping to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acutely induced episodes of AF. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms, with a demonstrated range of discordance between the epicardial and endocardial dynamic propagation patterns. After confirming the presence of epi-endo dyssynchrony in multiple animal models, we further investigated the anatomical structure to look for regional trends in transmural fiber orientation that could help explain the spectrum of observed patterns. Simultaneously, we designed and optimized a multi-stage, multi-path defibrillation paradigm that can be tailored to individual AF frequency content in the spatial and temporal domain. These studies continue to drive down the defibrillation threshold of electrotherapies in an attempt to achieve a pain-free AF defibrillation solution. Finally, we designed and characterized a novel platform of stretchable electronics that provide instrumented membranes across the epicardial surface or implanted within the transmural wall to provide physiological feedback during electrotherapy beyond just the electrical state of the tissue. By combining a spatial analysis of the arrhythmia drivers, the energy delivered and the resulting damage, we hope to enhance the biophysical understanding of AF electrical cardioversion and xiii design an ideal targeted energy delivery protocol to improve upon all limitations of current electrotherapy

    New concepts for use in low-energy cardiac defibrillation

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    The presence of three-dimensional rotating action potential waves, called scroll waves, in the heart causes ventricular fibrillation. Recently, there has been interest in developing low-energy methods, consisting of applying an electric field to terminate these waves, as a means of defibrillation. The success of these methods often depends on the orientation of the waves. We present computer simulations of a method that applies multiple electrical fields in a hemispherical shell system representative of the ventricles of the heart. Scroll waves in this system persist when the filament (the curve around which the wave rotates) connects the inside and outside surfaces. Our scheme for applying electric fields aims to disconnect these filaments from the surfaces. Once the filaments no longer connect the inside and outside surfaces, they contract and disappear, terminating the scroll wave. Importantly, as opposed to most existing schemes, the idea on which this scheme is based is applicable irrespective of how many scroll waves are present, where they are located, or where they are in their rotation. We discuss the success of this scheme both for different numbers of waves and for different wave orientations and present potential failure mechanisms. The effects of other conditions, such as the stability of the waves and heart geometry, remain to be studied. In the future, the presented low-energy method for termination of scroll waves may be a useful means of cardiac defibrillation

    Design and clinical validation of novel imaging strategies for analysis of arrhythmogenic substrate

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    _CURRENT CHALLENGES IN ELECTROPHYSIOLOGY_ Technical advances in cardiovascular electrophysiology have resulted in an increasing number of catheter ablation procedures reaching 200 000 in Europe for the year 2013. These advanced interventions are often complex and time consuming and may cause significant radiation exposure. Furthermore, a substantial number of ablation procedures remain associated with poor (initial) outcomes and frequently require ≥1 redo procedures. Innovations in modalities for substrate imaging could facilitate our understanding of the arrhythmogenic substrate, improve the design of patient-specific ablation strategies and improve the results of ablation procedures. _NOVEL SUBSTRATE IMAGING MODALITIES_ __Cardiac magnetic resonance__ Cardiac magnetic resonance imaging (CMR) can be considered the most comprehensive and suitable modality for the complete electrophysiology and catheter ablation workup (including patient selection, procedural guidance, and [procedural] follow-up). Utilizing inversion recovery CMR, fibrotic myocardium can be visualized and quantified 10–15 min after intravenous administration of Gadolinium contrast. This imaging technique is known as late Gadolinium enhancement (LGE) imaging. Experimental models have shown excellent agreement between size and shape in LGE CMR and areas of myocardial infarction by histopathology. Recent studies have also demonstrated how scar size, shape and location from pre-procedural LGE can be useful in guiding ventricular tachycardia’s (VT) ablation or atrial fibrillation (AF) ablation. These procedures are often time-consuming due to the preceding electrophysiological mapping study required to identify slow conduction zones involved in re-entry circuits. Post-processed LGE images provide scar maps, which could be integrated with electroanatomic mapping systems to facilitate these procedures. __Inverse potential mapping__ Through the years, various noninvasive electrocardiographic imaging techniques have emerged that estimate epicardial potentials or myocardial activation times from potentials recorded on the thorax. Utilizing an inverse procedure, the potentials on the heart surface or activation times of the myocardium are estimated with the recorded body surface potentials as source data. Although this procedure only estimates the time course of unipolar epicardial electrograms, several studies have demonstrated that the epicardial potentials and electrograms provide substantial information about intramyocardial activity and have great potential to facilitate risk-stratification and generate personalized ablation strategies. __Objectives of this thesis__ 1. To evaluate the utility of cardiac magnetic resonance derived geometrical and tissue characteristic information for patient stratification and guidance of AF ablation. 2. To design and evaluate the performance of a finite element model based inverse potential mapping in predicting the arrhythmogenic focus in idiopathic ventricular tachycardia using invasive electro-anatomical activation mapping as a reference standard

    Current Issues and Recent Advances in Pacemaker Therapy

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    Patients with implanted pacemakers or defibrillators are frequently encountered in various healthcare settings. As these devices may be responsible for, or contribute to a variety of clinically significant issues, familiarity with their function and potential complications facilitates patient management. This book reviews several clinically relevant issues and recent advances of pacemaker therapy: implantation, device follow-up and management of complications. Innovations and research on the frontiers of this technology are also discussed as they may have wider utilization in the future. The book should provide useful information for clinicians involved in the management of patients with implanted antiarrhythmia devices and researchers working in the field of cardiac implants
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