Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (58 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2013)

The cardiac sympathetic nervous system (SNS) exerts profound influence on

ventricular myocardial excitability. Disturbances in excitability result in ventricular arrhythmias (VAs). Remodeling of cardiac SNS is associated with risk of VAs, however the mechanistic underpinnings of this relationship remain poorly understood.

To characterize structural intra-cardiac (ventricular) SNS remodeling (ICNR),

ventricular myocardium from humans and porcine with ischemic or non-ischemic cardiomyopathy (ICM and NICM respectively), and normal controls (CON) of both species were subjected to detailed histologic and immuno-histochemical (IHC) analyses. Similarly, structural characterization of extra-cardiac neural remodeling (ECNR) within left and right stellate ganglia (LSG and RSG respectively) were performed using histologic and IHC methods to determine neuronal characteristics in normal vs. ICM and NICM. Lastly, the functional consequences of ICNR and ECNR were studied in porcine with myocardial infarcts (MI), and compared to CON.

In myocardium, structural sympathetic nerve remodeling consists of increased

sympathetic nerve density at border-zones of scar and normal myocardium. In stellate ganglia of humans with ICM and NICM (and porcine with MI), neuronal size was significantly increased. LSG and RSG from porcine with MI, also showed a decrease in the percentage of non-adrenergic neurons, compared to CON, indicating that ECNR also consisted of a shift from non-adrenergic to adrenergic phenotypes. Functional mapping of myocardial activation recovery intervals (ARIs), an accepted surrogate for action potential duration (APD) in normal porcine hearts showed that RSG innervation predominated on the anterior wall, while LSG innervation predominated on the posterior wall. After MI, ICNR and ECNR resulted in loss of innervation patterns seen in normal. Further, dispersion of repolarization (DOR) was increased in the infarct and border zone

regions of infarcted porcine compared to other cardiac regions, but this was not the case in CON. In addition, global DOR (including or excluding the infarct zones) was greater in the hearts of infarcted animals compared to normal controls.

In conclusion, following MI significant remodeling of stellate ganglion neurons,

and nerve terminals within the heart occurs. This results in significant functional alteration of innervation patterns, and worsening of repolarization heterogeneity. These mechanisms partly explain the association between SNS remodeling and arrhythmogenesis.

    Cover page: Intra- and Extra-Cardiac Neural Remodeling In Mammalian Ventricle: Implications For Arrhythmogenesis.
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2014)
    Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT.
      Cover page: Ventricular tachycardia in ischemic heart disease substrates.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2016)
      His bundle pacing is increasingly used to avoid chronic right ventricular pacing, and electrically resynchronize ventricular activation by narrowing or normalizing the QRS interval in left and right bundle branch block. The mechanisms by which this occurs remain poorly understood. In this review, the proposed mechanisms and evidence supporting them are discussed. Also discussed are aspects of mechanisms that are not completely supported by the evidence. We also review the differences and physiological bases for direct vs. indirect His bundle capture, and the physiological mechanisms for QRS narrowing vs. normalization following His bundle pacing.
        Cover page: Physiological mechanisms of QRS narrowing in bundle branch block patients undergoing permanent His bundle pacing
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2019)
        PURPOSE OF REVIEW:This review aims to describe the latest advances in autonomic neuromodulation approaches to treating cardiac arrhythmias, with a focus on ventricular arrhythmias. RECENT FINDINGS:The increasing understanding of neuronal remodeling in cardiac diseases has led to the development and improvement of novel neuromodulation therapies targeting multiple levels of the autonomic nervous system. Thoracic epidural anesthesia, spinal cord stimulation, stellate ganglion modulatory therapies, vagal stimulation, renal denervation, and interventions on the intracardiac nervous system have all been studied in preclinical models, with encouraging preliminary clinical data. The autonomic nervous system regulates all the electrical processes of the heart and plays an important role in the pathophysiology of cardiac arrhythmias. Despite recent advances in the clinical application of cardiac neuromodulation, our comprehension of the anatomy and function of the cardiac autonomic nervous system is still limited. Hopefully in the near future, more preclinical data combined with larger clinical trials will lead to further improvements in neuromodulatory treatment for heart rhythm disorders.
          Cover page: Neuromodulation Approaches for Cardiac Arrhythmias: Recent Advances
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2014)
          Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            Atrial fibrillation (AF) is the most common arrhythmia prompting clinical presentation, is associated with significant morbidity and mortality. The incidence and prevalence of this arrhythmia is expected to grow significantly in the coming decades. Of the available pharmacologic and non-pharmacologic treatment options, the fastest growing and most intensely studied is catheter-based ablation therapy for AF. Given the varying success rates for AF ablation, the increasingly complex factors that need to be taken into account when deciding to proceed with ablation, as well as varying definitions of procedural success, accurate detection of arrhythmia recurrence and its burden is of significance. Detecting and monitoring AF recurrence following catheter ablation is therefore an important consideration. Multiple studies have demonstrated the close relationship between the intensity of rhythm monitoring with wearable ambulatory cardiac monitors, or implantable cardiac rhythm monitors and the detection of arrhythmia recurrence. Other studies have employed algorithms dependent on intensive monitoring and arrhythmia detection in the decision tree on whether to proceed with repeat ablation or medical therapy. In this review, we discuss these considerations, types of monitoring devices, and implications for monitoring AF recurrence following catheter ablation.
              Cover page: Detecting and monitoring arrhythmia recurrence following catheter ablation of atrial fibrillation
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2023)
              Photogrammetry generates a 3-dimensional high-resolution model from multiple 2-dimensional photographs. Herein, we demonstrate a photogrammetry of a perfusion-fixed cardiac sample around the left ventricular summit. The single photogrammetric model can be observed from almost all directions and illustrates important anatomical features for the general cardiologist. (Level of Difficulty: Advanced.).
                Cover page: Photogrammetry of Perfusion-Fixed Heart: Innovative Approach to Study 3-Dimensional Cardiac Anatomy.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2021)

                Purpose

                This review aimed to provide a complete overview of the current stance and recent developments in antiarrhythmic neuromodulatory interventions, focusing on lifethreatening vetricular arrhythmias.

                Methods

                Both preclinical studies and clinical studies were assessed to highlight the gaps in knowledge that remain to be answered and the necessary steps required to properly translate these strategies to the clinical setting.

                Results

                Cardiac autonomic imbalance, characterized by chronic sympathoexcitation and parasympathetic withdrawal, destabilizes cardiac electrophysiology and promotes ventricular arrhythmogenesis. Therefore, neuromodulatory interventions that target the sympatho-vagal imbalance have emerged as promising antiarrhythmic strategies. These strategies are aimed at different parts of the cardiac neuraxis and directly or indirectly restore cardiac autonomic tone. These interventions include pharmacological blockade of sympathetic neurotransmitters and neuropeptides, cardiac sympathetic denervation, thoracic epidural anesthesia, and spinal cord and vagal nerve stimulation.

                Conclusion

                Neuromodulatory strategies have repeatedly been demonstrated to be highly effective and very promising anti-arrhythmic therapies. Nevertheless, there is still much room to gain in our understanding of neurocardiac physiology, refining the current neuromodulatory strategic options and elucidating the chronic effects of many of these strategic options.
                  Cover page: Autonomic modulation of ventricular electrical activity: recent developments and clinical implications
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2021)

                  Cardiovascular autonomic dysfunction (AD) among cancer survivors is increasingly being recognized. However, the mechanisms and incidence are poorly understood. In this review, the clinical features, diagnostic modalities, proposed mechanisms, and currently available treatments of cardiovascular AD in cancer survivors are described.

                  Much of our current understanding of cardiovascular AD is based on disease states such as diabetes, multisystem atrophy, and Parkinson's disease. Several non-invasive tests, measurements, and scoring systems have been developed as surrogates for autonomic function, with some even demonstrating associations with all-cause mortality. The mechanism of cardiovascular AD specifically in the cancer population, however, has not been directly studied. The etiology of cardiovascular AD in cancer survivors is likely multifactorial, and proposed mechanisms include direct nerve damage by chemoradiation, the pro-inflammatory state associated with malignancy, and paraneoplastic syndromes. It may also be that cardiovascular AD is an early marker of global cardiomyopathy rather than its own condition. Current pharmacologic options for cardiovascular AD are extrapolated from how it has been treated in other disease processes, and these agents have not been studied in the cancer population or compared head-to-head. Cardiovascular AD in cancer survivors can cause significant debilitation and may be associated with all-cause mortality. Current diagnostic modalities have several limitations, such as standardization and validity. However, given the nonspecific nature of cardiovascular AD, these tools provide an objective marker for diagnosis and tracking treatment response. While the mechanism of cardiovascular AD in cancer survivors has not been directly studied, it may be useful to evoke mechanisms of cardiovascular AD in other disease states such as diabetes, Parkinson's disease, and multisystem atrophy in addition to identifying unique conditions associated with malignancy like a pro-inflammatory state. Until further studies are performed, management of cardiovascular AD as seen in other disease states may serve as a guide for symptom management in cancer survivors.

                    Cover page: Chemotherapy and Radiation-Associated Cardiac Autonomic Dysfunction.
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2017)

                    Background

                    The efficacy of percutaneous stellate ganglion block (SGB) for managing electrical storm (ES) is not well understood.

                    Objective

                    To characterize the efficacy of SGB as a treatment for ES.

                    Methods

                    We conducted literature searches using PubMed/Medline and Google Scholar, for mixed combinations of terms including "stellate ganglion block", *ganglion block (ade)", "sympathetic block (ade)" and "arrhythmia", "ventricular arrhythmia (VA)" or "tachycardia" (VT), "ventricular fibrillation" (VF), "electrical storm". Inclusion criteria were presentation with guideline-defined ES and treatment with SGB. Exclusion criteria: presentation with any supraventricular arrhythmia, VA without ES, or surgical sympathectomy. Studies lacking basic demographic data, arrhythmia description, and outcomes were excluded.

                    Results

                    Of 3,374 publications reviewed, 38 patients from 23 studies met study criteria (52 ± 19.1 years, 11 F, 17 with ischemic cardiomyopathy). Anti-arrhythmics were used in all patients. Mean Left ventricular ejection fraction was 31 ± 10%. ES was triggered by acute myocardial infarction in 15 patients and QT prolongation in 7 patients. The most common local anesthetic used for SGB was bupivacaine (0.25-0.5%). SGB resulted in a significant decrease in VA burden (12.4±8.8 vs. 1.04±2.12 episodes/day, p< 0.001) and number of external and ICD shocks (10.0±9.1 vs. 0.05±0.22 shocks/day, p< 0.01). Following SGB, 80.6% of patients survived to discharge.

                    Conclusion

                    SGB is an effective acute treatment for ES. However, larger prospective randomized studies are needed to better understand the role of SGB in ES and other VAs.
                      Cover page: Efficacy of Stellate Ganglion Blockade in&nbsp;Managing Electrical Storm A Systematic Review
                      Top