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Trends in Cardiovascular Medicine Jul 2020Bradycardia is a commonly observed arrhythmia and a frequent occasion for cardiac consultation. Defined as a heart rate of less than 50-60 bpm, bradycardia can be... (Review)
Review
Bradycardia is a commonly observed arrhythmia and a frequent occasion for cardiac consultation. Defined as a heart rate of less than 50-60 bpm, bradycardia can be observed as a normal phenomenon in young athletic individuals, and in patients as part of normal aging or disease (Table 1). Pathology that produces bradycardia may occur within the sinus node, atrioventricular (AV) nodal tissue, and the specialized His-Purkinje conduction system. Given the overlap of heart rate ranges with non-pathologic changes, assessment of symptoms is a critical component in the evaluation and management of bradycardia. Treatment should rarely be prescribed solely on the basis of a heart rate lower than an arbitrary cutoff or a pause above certain duration. In the 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay (referred to hereafter as the 2018 Bradycardia Guideline), there was a significant shift in emphasis from prior guidelines that emphasized device-based implantation recommendations to a focus on evaluation and management of disease states [1,2]. In this review, we will highlight the changes in the new guideline as well as describe the key elements in evaluation and management of patients presenting with bradycardia.
Topics: Action Potentials; Atrioventricular Block; Bradycardia; Cardiac Pacing, Artificial; Clinical Decision-Making; Heart Conduction System; Heart Rate; Humans; Pacemaker, Artificial; Patient Selection; Sick Sinus Syndrome; Treatment Outcome
PubMed: 31311698
DOI: 10.1016/j.tcm.2019.07.001 -
Circulation Oct 2020Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and... (Review)
Review
Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient's arrythmia could be drug-induced is important.
Topics: American Heart Association; Arrhythmias, Cardiac; Electrocardiography; Risk Factors; United States
PubMed: 32929996
DOI: 10.1161/CIR.0000000000000905 -
Frontiers in Cardiovascular Medicine 2021Cardiac pacing is an effective therapy for treating patients with bradycardia due to sinus node dysfunction or atrioventricular block. However, traditional right... (Review)
Review
Cardiac pacing is an effective therapy for treating patients with bradycardia due to sinus node dysfunction or atrioventricular block. However, traditional right ventricular apical pacing (RVAP) causes electric and mechanical dyssynchrony, which is associated with increased risk for atrial arrhythmias and heart failure. Therefore, there is a need to develop a physiological pacing approach that activates the normal cardiac conduction and provides synchronized contraction of ventricles. Although His bundle pacing (HBP) has been widely used as a physiological pacing modality, it is limited by challenging implantation technique, unsatisfactory success rate in patients with wide QRS wave, high pacing capture threshold, and early battery depletion. Recently, the left bundle branch pacing (LBBP), defined as the capture of left bundle branch (LBB) via transventricular septal approach, has emerged as a newly physiological pacing modality. Results from early clinical studies have demonstrated LBBP's feasibility and safety, with rare complications and high success rate. Overall, this approach has been found to provide physiological pacing that guarantees electrical synchrony of the left ventricle with low pacing threshold. This was previously specifically characterized by narrow paced QRS duration, large R waves, fast synchronized left ventricular activation, and correction of left bundle branch block. Therefore, LBBP may be a potential alternative pacing modality for both RVAP and cardiac resynchronization therapy with HBP or biventricular pacing (BVP). However, the technique's widespread adaptation needs further validation to ascertain its safety and efficacy in randomized clinical trials. In this review, we discuss the current knowledge of LBBP.
PubMed: 33834042
DOI: 10.3389/fcvm.2021.630399 -
Arrhythmia & Electrophysiology Review Apr 2022The name Ivan Mahaim is well-known to electrophysiologists. However, alternative anatomical substrates can produce the abnormal rhythms initially interpreted on the... (Review)
Review
The name Ivan Mahaim is well-known to electrophysiologists. However, alternative anatomical substrates can produce the abnormal rhythms initially interpreted on the basis of the pathways he first described. These facts have prompted suggestions that Mahaim should be deprived of his eponym. It is agreed that specificity is required when describing the pathways that produce the disordered cardiac conduction, and that the identified pathways should now be described in an attitudinally appropriate fashion. The authors remain to be convinced that understanding will be enhanced simply by discarding the term 'Mahaim physiology' from the lexicon. It is fascinating to look back at the history of accessory atrioventricular junctional conduction pathways outside the normal accessory atrioventricular conduction system, and their possible role in rhythm disturbances. It took both the anatomist and the clinical arrhythmologist quite some time to understand the complex anatomical architecture and the ensuing electrophysiological properties. Over the years, the name Mahaim was often mentioned in those discussions, although these pathways were not the ones that produced the eponym. The reason for this review, therefore, is to present relevant information about the person and what followed thereafter.
PubMed: 35990105
DOI: 10.15420/aer.2022.12 -
Frontiers in Pharmacology 2020This review is focusing on the understanding of various factors and components governing and controlling the occurrence of ventricular arrhythmias including (i) the role... (Review)
Review
This review is focusing on the understanding of various factors and components governing and controlling the occurrence of ventricular arrhythmias including (i) the role of various ion channel-related changes in the action potential (AP), (ii) electrocardiograms (ECGs), (iii) some important arrhythmogenic mediators of reperfusion, and pharmacological approaches to their attenuation. The transmembrane potential in myocardial cells is depending on the cellular concentrations of several ions including sodium, calcium, and potassium on both sides of the cell membrane and active or inactive stages of ion channels. The movements of Na, K, and Ca cell membranes produce various currents that provoke AP, determining the cardiac cycle and heart function. A specific channel has its own type of gate, and it is opening and closing under specific transmembrane voltage, ionic, or metabolic conditions. APs of sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje cells determine the pacemaker activity (depolarization phase 4) of the heart, leading to the surface manifestation, registration, and evaluation of ECG waves in both animal models and humans. AP and ECG changes are key factors in arrhythmogenesis, and the analysis of these changes serve for the clarification of the mechanisms of antiarrhythmic drugs. The classification of antiarrhythmic drugs may be based on their electrophysiological properties emphasizing the connection between basic electrophysiological activities and antiarrhythmic properties. The review also summarizes some important mechanisms of ventricular arrhythmias in the ischemic/reperfused myocardium and permits an assessment of antiarrhythmic potential of drugs used for pharmacotherapy under experimental and clinical conditions.
PubMed: 32477118
DOI: 10.3389/fphar.2020.00616 -
Nature Jun 2022The sympathetic and parasympathetic nervous systems regulate the activities of internal organs, but the molecular and functional diversity of their constituent neurons...
The sympathetic and parasympathetic nervous systems regulate the activities of internal organs, but the molecular and functional diversity of their constituent neurons and circuits remains largely unknown. Here we use retrograde neuronal tracing, single-cell RNA sequencing, optogenetics and physiological experiments to dissect the cardiac parasympathetic control circuit in mice. We show that cardiac-innervating neurons in the brainstem nucleus ambiguus (Amb) are comprised of two molecularly, anatomically and functionally distinct subtypes. The first, which we call ambiguus cardiovascular (ACV) neurons (approximately 35 neurons per Amb), define the classical cardiac parasympathetic circuit. They selectively innervate a subset of cardiac parasympathetic ganglion neurons and mediate the baroreceptor reflex, slowing heart rate and atrioventricular node conduction in response to increased blood pressure. The other, ambiguus cardiopulmonary (ACP) neurons (approximately 15 neurons per Amb) innervate cardiac ganglion neurons intermingled with and functionally indistinguishable from those innervated by ACV neurons. ACP neurons also innervate most or all lung parasympathetic ganglion neurons-clonal labelling shows that individual ACP neurons innervate both organs. ACP neurons mediate the dive reflex, the simultaneous bradycardia and bronchoconstriction that follows water immersion. Thus, parasympathetic control of the heart is organized into two parallel circuits, one that selectively controls cardiac function (ACV circuit) and another that coordinates cardiac and pulmonary function (ACP circuit). This new understanding of cardiac control has implications for treating cardiac and pulmonary diseases and for elucidating the control and coordination circuits of other organs.
Topics: Animals; Cardiovascular System; Heart; Lung; Medulla Oblongata; Mice; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Optogenetics; Parasympathetic Nervous System; RNA-Seq; Single-Cell Analysis
PubMed: 35650438
DOI: 10.1038/s41586-022-04760-8 -
Circulation Research Aug 2019The cardiac conduction system (CCS) consists of distinct components including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje...
RATIONALE
The cardiac conduction system (CCS) consists of distinct components including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers. Despite an essential role for the CCS in heart development and function, the CCS has remained challenging to interrogate because of inherent obstacles including small cell numbers, large cell-type heterogeneity, complex anatomy, and difficulty in isolation. Single-cell RNA-sequencing allows for genome-wide analysis of gene expression at single-cell resolution.
OBJECTIVE
Assess the transcriptional landscape of the entire CCS at single-cell resolution by single-cell RNA-sequencing within the developing mouse heart.
METHODS AND RESULTS
Wild-type, embryonic day 16.5 mouse hearts (n=6 per zone) were harvested and 3 zones of microdissection were isolated, including: Zone I-sinoatrial node region; Zone II-atrioventricular node/His region; and Zone III-bundle branch/Purkinje fiber region. Tissue was digested into single-cell suspensions, cells isolated, mRNA reverse transcribed, and barcoded before high-throughput sequencing and bioinformatics analyses. Single-cell RNA-sequencing was performed on over 22 000 cells, and all major cell types of the murine heart were successfully captured including bona fide clusters of cells consistent with each major component of the CCS. Unsupervised weighted gene coexpression network analysis led to the discovery of a host of novel CCS genes, a subset of which were validated using fluorescent in situ hybridization as well as whole-mount immunolabeling with volume imaging (iDISCO+) in 3 dimensions on intact mouse hearts. Further, subcluster analysis unveiled isolation of distinct CCS cell subtypes, including the clinically relevant but poorly characterized transitional cells that bridge the CCS and surrounding myocardium.
CONCLUSIONS
Our study represents the first comprehensive assessment of the transcriptional profiles from the entire CCS at single-cell resolution and provides a characterization in the context of development and disease.
Topics: Animals; Heart Conduction System; Mice; RNA-Seq; Single-Cell Analysis; Transcriptome
PubMed: 31284824
DOI: 10.1161/CIRCRESAHA.118.314578