Autonomic nervous system control of the heart is a dynamic process in both health and disease. A multilevel neural network is responsible for control of chronotropy, lusitropy, dromotropy, and ...inotropy. Intrinsic autonomic dysfunction arises from diseases that directly affect the autonomic nerves, such as diabetes mellitus and the syndromes of primary autonomic failure. Extrinsic autonomic dysfunction reflects the changes in autonomic function that are secondarily induced by cardiac or other disease. An array of tests interrogate various aspects of cardiac autonomic control in either resting conditions or with physiological perturbations from resting conditions. The prognostic significance of these assessments have been well established. Clinical usefulness has not been established, and the precise mechanistic link to mortality is less well established. Further efforts are required to develop optimal approaches to delineate cardiac autonomic dysfunction and its adverse effects to develop tools that can be used to guide clinical decision-making.
We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for ...generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing.
Permanent His-bundle pacing (HBP) has the potential to physiologically normalize wide QRS duration in patients with bundle branch block and cardiomyopathy.
The purpose of this study was to assess the ...feasibility of incorporating a His-bundle lead for cardiac resynchronization therapy (CRT) in lieu of a coronary sinus lead.
Patients with an indication for CRT (n = 21) underwent attempted implantation of an HBP placed into the left ventricular (LV) lead port. Intracardiac intervals, QRS duration, New York Heart Association functional class, ejection fraction (EF), echocardiography, and lead characteristics were measured at baseline and at follow-up.
Of the 21 patients in whom implantation was attempted, HBP was successfully implanted in 16 (age 62 ± 18 years, 4 females, EF 25 ± 8). A significant reduction in mean QRS was observed, with narrowing from 180 ± 23 ms to 129 ± 13 ms (P <.0001). During the follow-up period, median New York Heart Association functional class improved from III to II (P <.001), and mean LV EF and left ventricular internal dimension in diastole (LVIDd) improved from 27% ± 10% to 41% ± 13% (P <.001) and from 5.4 ± 0.4 cm to 4.5 ± 0.3 cm (P <.001), respectively. At median 12-month follow-up, no dislodgments were observed, and only one patient lost nonselective capture that resolved with increased pacing output.
Permanent HBP is feasible for patients with an indication for CRT using the LV port in lieu of a coronary sinus lead. In this initial experience, narrowing of QRS duration was achieved in 76% of patients with bundle branch block, and improvements in clinical and echocardiographic measures were observed with HBP. Future prospective comparative studies with HBP to achieve CRT are justifiable.
The long QT syndrome (LQTS) is largely treated pharmacologically with β‐blockers, despite the role of sympathetic activity in LQTS being poorly understood. Using the trigger–substrate model of ...cardiac arrhythmias in this review, we amalgamate current experimental and clinical data from both animal and human studies to explain the mechanism of adrenergic stimulation and blockade on LQT arrhythmic risk and hence assess the efficacy of β‐adrenoceptor blockade in the management of LQTS. In LQTS1 and LQTS2, sympathetic stimulation increases arrhythmic risk by enhancing early afterdepolarizations and transmural dispersion of repolarization. β‐Blockers successfully reduce cardiac events by reducing these triggers and substrates; however, these effects are less marked in LQTS2 compared with LQTS1. In LQTS3, clinical and experimental investigations of the effects of sympathetic stimulation and β‐blocker use have produced contradictory findings, resulting in significant clinical uncertainty. We offer explanations for these contradicting results relating to study sample size, the dose of the β‐blocker administered associated with its off‐target Na+ channel effects, as well as the type of β‐blocker used. We conclude that the antiarrhythmic efficacy of β‐blockers is a genotype‐specific phenomenon, and hence the use of β‐blockers in clinical practice should be genotype dependent.
Our review amalgamates current experimental and clinical data from both animal and human studies to explain the mechanism of adrenergic stimulation and blockade on LQT arrhythmic risk and hence assess the efficacy of β‐adrenoceptor blockade in the management of LQTS.
Abstract Background Cardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart ...disease (SHD) and recurrent ventricular tachyarrhythmias (VT). Objectives This study assessed the value of CSD and the characteristics associated with outcomes in this population. Methods Patients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD. Results Between 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided–only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up. Conclusions CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided–only procedure.
Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). ...Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.
Understanding three‐dimensional cardiac anatomy is fundamental for the practice of clinical cardiology. However, if three‐dimensional images are displayed on two‐dimensional monitors, they fail to ...provide depth perception. Currently, novel technologies, including the three‐dimensional printing, three‐dimensional monitors/projectors, and virtual reality applications can provide real three‐dimensionality with depth perception. However, their relatively high cost and limited user‐friendliness prevent their wide application. We introduce novel and commercially available holographic display, which allows multiple observers to see the full‐color holographic images simultaneously without any specific glasses and headgear. This leading‐edge technology is immediately applicable in both educational and clinical settings.
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