Electrophysiologic Characterization of the Arrhythmogenic Substrate in Reentrant Atrial and Ventricular Arrhythmias Insights from the Clinical and Experimental Electrophysiology Laboratories

This thesis encompasses an overview and critical analysis of 11 publications of clinical and translational cardiac electrophysiology research that has been executed over the last seven years. The focus of this dissertation and the selected papers is on the use of electroanatomic mapping technology to define the arrhythmogenic substrate in patients with structural heart disease and ventricular arrhythmias. Such advancements in elucidating the mechanisms and pathophysiology underlying scar-related ventricular tachycardia have yielded improved clinical outcomes for patients with drug-refractory ventricular arrhythmias. Chapter 1 describes the epidemiologic background and introduces the concept of intracardiac mapping and the technological evolution that has provided the basis for this current body of work. Chapter 2 and Chapter 3 provide a detailed description of how electroanatomic mapping studies have provided critical insight into disease pathogenesis in patients with dilated nonischemic cardiomyopathy arrhythmogenic right ventricular cardiomyopathy (ARVC). The clinical impact and relevance of these studies are discussed based on conventional electroanatomic mapping technologies to define abnormal physiological substrates. Chapter 3 also addresses important considerations regarding percutaneous epicardial mapping and ablation that have been derived from extensive clinical experience. Chapter 4 and Chapter 5 describe the evolution of mapping technologies and the use of high-resolution mapping system technologies. These chapters discuss the potential clinical advantages of these technologies during substrate and activation mapping, particularly in post-infarct ventricular scar and VT. Finally, Chapter 6 concludes this thesis with final thoughts on the broader context of the lessons that have been learned from the studies that are presented in this thesis and implications for future work

Compensation for unconstrained catheter shaft motion in cardiac catheters

Abstract— Cardiac catheterization with ultrasound (US) imaging catheters provides real time US imaging from within the heart, but manually navigating a four degree of freedom (DOF) imaging catheter is difficult and requires extensive training. Existing work has demonstrated robotic catheter steering in constrained bench top environments. Closed-loop control in an unconstrained setting, such as patient vasculature, remains a significant challenge due to friction, backlash, and physiological disturbances. In this paper we present a new method for closed-loop control of the catheter tip that can accurately and robustly steer 4-DOF cardiac catheters and other flexible manipulators despite these effects. The performance of the system is demonstrated in a vasculature phantom and an in vivo porcine animal model. During bench top studies the robotic system converged to the desired US imager pose with submillimeter and sub-degree-level accuracy. During animal trials the system achieved 2.0 mm and 0.65° accuracy. Accurate and robust robotic navigation of flexible manipulators will enable enhanced visualization and treatment during procedures.Engineering and Applied Science

Instrument Tracking and Visualization for Ultrasound Catheter Guided Procedures

We present an instrument tracking and visualization system for intra-cardiac ultrasound catheter guided procedures, enabled through the robotic control of ultrasound catheters. Our system allows for rapid acquisition of 2D ultrasound images and accurate reconstruction and visualization of a 3D volume. The reconstructed volume addresses the limited field of view, an inherent problem of ultrasound imaging, and serves as a navigation map for procedure guidance. Our robotic system can track a moving instrument by continuously adjusting the imaging plane and visualizing the instrument tip. The overall instrument tracking accuracy is 2.2mm RMS in position and 0.8◦ in angleEngineering and Applied Science

Esophageal cooling for protection during left atrial ablation : a systematic review and meta-analysis

Thermal damage to the esophagus is a risk from radiofrequency (RF) ablation of the left atrium for the treatment of atrial fibrillation (AF). The most extreme type of thermal injury results in atrio-esophageal fistula (AEF) and a correspondingly high mortality rate. Various strategies for reducing esophageal injury have been developed, including power reduction, esophageal deviation, and esophageal cooling. One method of esophageal cooling involves the direct instillation of cold water or saline into the esophagus during RF ablation. Although this method provides limited heat-extraction capacity, studies of it have suggested potential benefit. We sought to perform a meta-analysis of published studies evaluating the use of esophageal cooling via direct liquid instillation for the reduction of thermal injury during RF ablation. We searched PubMed for studies that used esophageal cooling to protect the esophagus from thermal injury during RF ablation. We then performed a meta-analysis using a random effects model to calculate estimated effect size with 95% confidence intervals, with an outcome of esophageal lesions stratified by severity, as determined by post-procedure endoscopy. A total of 9 studies were identified and reviewed. After excluding preclinical and mathematical model studies, 3 were included in the meta-analysis, totaling 494 patients. Esophageal cooling showed a tendency to shift lesion severity downward, such that total lesions did not show a statistically significant change (OR 0.6, 95% CI 0.15 to 2.38). For high-grade lesions, a significant OR of 0.39 (95% CI 0.17 to 0.89) in favor of esophageal cooling was found, suggesting that esophageal cooling, even with a low-capacity thermal extraction technique, reduces the severity of lesions resulting from RF ablation. Esophageal cooling reduces the severity of the lesions that may result from RF ablation, even when relatively low heat extraction methods are used, such as the direct instillation of small volumes of cold liquid. Further investigation of this approach is warranted, particularly with higher heat extraction capacity techniques

Esophageal cooling for protection during left atrial ablation: a systematic review and meta-analysis.

PURPOSE: Thermal damage to the esophagus is a risk from radiofrequency (RF) ablation of the left atrium for the treatment of atrial fibrillation (AF). The most extreme type of thermal injury results in atrio-esophageal fistula (AEF) and a correspondingly high mortality rate. Various strategies for reducing esophageal injury have been developed, including power reduction, esophageal deviation, and esophageal cooling. One method of esophageal cooling involves the direct instillation of cold water or saline into the esophagus during RF ablation. Although this method provides limited heat-extraction capacity, studies of it have suggested potential benefit. We sought to perform a meta-analysis of published studies evaluating the use of esophageal cooling via direct liquid instillation for the reduction of thermal injury during RF ablation. METHODS: We searched PubMed for studies that used esophageal cooling to protect the esophagus from thermal injury during RF ablation. We then performed a meta-analysis using a random effects model to calculate estimated effect size with 95% confidence intervals, with an outcome of esophageal lesions stratified by severity, as determined by post-procedure endoscopy. RESULTS: A total of 9 studies were identified and reviewed. After excluding preclinical and mathematical model studies, 3 were included in the meta-analysis, totaling 494 patients. Esophageal cooling showed a tendency to shift lesion severity downward, such that total lesions did not show a statistically significant change (OR 0.6, 95% CI 0.15 to 2.38). For high-grade lesions, a significant OR of 0.39 (95% CI 0.17 to 0.89) in favor of esophageal cooling was found, suggesting that esophageal cooling, even with a low-capacity thermal extraction technique, reduces the severity of lesions resulting from RF ablation. CONCLUSIONS: Esophageal cooling reduces the severity of the lesions that may result from RF ablation, even when relatively low heat extraction methods are used, such as the direct instillation of small volumes of cold liquid. Further investigation of this approach is warranted, particularly with higher heat extraction capacity techniques

Mechanisms and Clinical Management of Ventricular Arrhythmias following Blunt Chest Trauma

Nonpenetrating, blunt chest trauma is a serious medical condition with varied clinical presentations and implications. This can be the result of a dense projectile during competitive and recreational sports but may also include other etiologies such as motor vehicle accidents or traumatic falls. In this setting, the manifestation of ventricular arrhythmias has been observed both acutely and chronically. This is based on two entirely separate mechanisms and etiologies requiring different treatments. Ventricular fibrillation can occur immediately after chest wall injury (commotio cordis) and requires rapid defibrillation. Monomorphic ventricular tachycardia can develop in the chronic stage due to underlying structural heart disease long after blunt chest injury. The associated arrhythmogenic tissue may be complex and provides the necessary substrate to form a reentrant VT circuit. Ventricular tachycardia in the absence of overt structural heart disease appears to be focal in nature with rapid termination during ablation. Regardless of the VT mechanism, patients with recurrent episodes, despite antiarrhythmic medication in the chronic stage following blunt chest injury, are likely to require ablation to achieve VT control. This review article will describe the mechanisms, pathophysiology, and treatment of ventricular arrhythmias that occur in both the acute and chronic stages following blunt chest trauma

Feasibility of electroanatomic mapping and radiofrequency catheter ablation in Boxer dogs with symptomatic ventricular tachycardia

Abstract Background Treatment for Boxers with ventricular tachycardia (VT) is limited. Electroanatomic mapping (EAM) facilitates identification of arrhythmogenic substrate for radiofrequency catheter ablation (RFCA). Objective Describe the use of EAM to guide RFCA in Boxers with VT. Animals Five client‐owned Boxers with symptomatic VT or persistent VT despite antiarrhythmic medications. Methods Case series evaluating clinical, EAM, and before and after RFCA Holter data. Results Sustained VT was inducible in 3 dogs, but required aggressive stimulation protocols. Low‐voltage areas consistent with electroanatomic scar were found in 2 dogs, located at the right ventricular (RV) outflow tract and cranial RV. Two dogs had a focal activation pattern of VT and 1 dog had a reentrant mechanism. After RFCA, all dogs no longer collapsed and had fewer runs of VT, 3 of which had 0 runs of VT. Number of ventricular premature beats increased in 3 dogs and decreased in 2 dogs, 1 of which had nearly complete resolution of all arrhythmias. Procedural complications included ventricular fibrillation (n = 2) with successful defibrillation, bruising or hemorrhage at the vascular access site (n = 4), retroperitoneal hemorrhage (n = 1), aortic and mitral regurgitation (n = 1), onset of frequent supraventricular tachycardia (n = 1), and persistent right pelvic limb lameness (n = 1). Conclusions and Clinical Importance Electroanatomic mapping and RFCA are feasible in Boxers with VT. Based on this small cohort, RFCA may help decrease runs of VT and improve clinical signs. The anatomic substrate and electrophysiologic mechanisms are variable and require further study

Overcoming challenges in the management of arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) appears in most patients to be an inherited disease characterized by fibrofatty replacement of myocytes extending from the epicardium to the endocardium in the right ventricle. The disease process results in life‑threatening ventricular arrhythmias and ventricular dysfunction. In the absence of a gold‑standard diagnostic test and despite the progress in imaging techniques, ARVC is often misdiagnosed and earlier detection of the disease is challenging. Preprocedural identification and localization of the substrate can be determined from the analysis of surface electrocardiography and cardiac magnetic resonance imaging. Typically, perivalvular arrhythmogenic substrate, defined by electroanatomic mapping, is present and can be isolated to the epicardium. Ablation targets are further identified with activation, entrainment, and local electrogram abnormalities based on detailed electroanatomic mapping. Extensive combined endo / epicardial ablation performed in experienced centers is frequently required to prevent ventricular tachycardia (VT). Catheter ablation significantly reduces recurrences of VT, appropriate implantable cardioverter‑defibrillator shocks, and the use of antiarrhythmic drugs and cardiac transplant as a management strategy for refractory arrhythmias is rarely required. Progression of the disease is poorly understood and may require a distinct triggering mechanism. Biventricular involvement is more common than previously recognized. However, left ventricular involvement leading to significant terminal heart failure is fortunately uncommon and left ventricular tachycardias are also infrequent. Many questions remain regarding prevention and management of coexisting tricuspid valve regurgitation, atrial arrhythmias, and intracardiac thrombosis. Although data on genotype‑phenotype correlations is growing, long‑term follow‑up studies of families with ARVC are still lacking. Ongoing research will contribute to better understanding of this pathological condition

Three-dimensional holographic visualization of high-resolution myocardial scar on HoloLens.

Visualization of the complex 3D architecture of myocardial scar could improve guidance of radio-frequency ablation in the treatment of ventricular tachycardia (VT). In this study, we sought to develop a framework for 3D holographic visualization of myocardial scar, imaged using late gadolinium enhancement (LGE), on the augmented reality HoloLens. 3D holographic LGE model was built using the high-resolution 3D LGE image. Smooth endo/epicardial surface meshes were generated using Poisson surface reconstruction. For voxel-wise 3D scar model, every scarred voxel was rendered into a cube which carries the actual resolution of the LGE sequence. For surface scar model, scar information was projected on the endocardial surface mesh. Rendered layers were blended with different transparency and color, and visualized on HoloLens. A pilot animal study was performed where 3D holographic visualization of the scar was performed in 5 swines who underwent controlled infarction and electroanatomic mapping to identify VT substrate. 3D holographic visualization enabled assessment of the complex 3D scar architecture with touchless interaction in a sterile environment. Endoscopic view allowed visualization of scar from the ventricular chambers. Upon completion of the animal study, operator and mapping specialist independently completed the perceived usefulness questionnaire in the six-item usefulness scale. Operator and mapping specialist found it useful (usefulness rating: operator, 5.8; mapping specialist, 5.5; 1-7 scale) to have scar information during the intervention. HoloLens 3D LGE provides a true 3D perception of the complex scar architecture with immersive experience to visualize scar in an interactive and interpretable 3D approach, which may facilitate MR-guided VT ablation