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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 -
American Family Physician Aug 2021Sinus node dysfunction, previously known as sick sinus syndrome, describes disorders related to abnormal conduction and propagation of electrical impulses at the... (Review)
Review
Sinus node dysfunction, previously known as sick sinus syndrome, describes disorders related to abnormal conduction and propagation of electrical impulses at the sinoatrial node. An abnormal atrial rate may result in the inability to meet physiologic demands, especially during periods of stress or physical activity. Sinus node dysfunction may occur at any age, but is usually more common in older persons. The causes of sinus node dysfunction are intrinsic (e.g., degenerative idiopathic fibrosis, cardiac remodeling) or extrinsic (e.g., medications, metabolic abnormalities) to the sinoatrial node. Many extrinsic causes are reversible. Electrocardiography findings include sinus bradycardia, sinus pauses or arrest, sinoatrial exit block, chronotropic incompetence, or alternating bradycardia and tachycardia (i.e., bradycardia-tachycardia syndrome). Clinical symptoms result from the hypoperfusion of end organs. About 50% of patients present with cerebral hypoperfusion (e.g., syncope, presyncope, lightheadedness, cerebrovascular accident). Other symptoms include palpitations, decreased physical activity tolerance, angina, muscular fatigue, or oliguria. A diagnosis is made by directly correlating symptoms with a bradyarrhythmia and eliminating potentially reversible extrinsic causes. Heart rate monitoring using electrocardiography or ambulatory cardiac event monitoring is performed based on the frequency of symptoms. An exercise stress test should be performed when symptoms are associated with exertion. The patient's inability to reach a heart rate of at least 80% of their predicted maximum (220 beats per minute - age) may indicate chronotropic incompetence, which is present in 50% of patients with sinus node dysfunction. First-line treatment for patients with confirmed sinus node dysfunction is permanent pacemaker placement with atrial-based pacing and limited ventricular pacing when necessary.
Topics: Cardiac Pacing, Artificial; Electrocardiography; Heart Rate; Humans; Sick Sinus Syndrome; Sinoatrial Node
PubMed: 34383451
DOI: No ID Found -
American Family Physician May 2013Sick sinus syndrome refers to a collection of disorders marked by the heart's inability to perform its pacemaking function. Predominantly affecting older adults, sick... (Review)
Review
Sick sinus syndrome refers to a collection of disorders marked by the heart's inability to perform its pacemaking function. Predominantly affecting older adults, sick sinus syndrome comprises various arrhythmias, including bradyarrhythmias with or without accompanying tachyarrhythmias. At least 50 percent of patients with sick sinus syndrome develop alternating bradycardia and tachycardia, also known as tachy-brady syndrome. Sick sinus syndrome results from intrinsic causes, or may be exacerbated or mimicked by extrinsic factors. Intrinsic causes include degenerative fibrosis, ion channel dysfunction, and remodeling of the sinoatrial node. Extrinsic factors can be pharmacologic, metabolic, or autonomic. Signs and symptoms are often subtle early on and become more obvious as the disease progresses. They are commonly related to end-organ hypoperfusion. Cerebral hypoperfusion is most common, with syncope or near-fainting occurring in about one-half of patients. Diagnosis may be challenging, and is ultimately made by electrocardiographic identification of the arrhythmia in conjunction with the presence of symptoms. If electrocardiography does not yield a diagnosis, inpatient telemetry monitoring, outpatient Holter monitoring, event monitoring, or loop monitoring may be used. Electrophysiologic studies also may be used but are not routinely needed. Treatment of sick sinus syndrome includes removing extrinsic factors, when possible, and pacemaker placement. Pacemakers do not reduce mortality, but they can decrease symptoms and improve quality of life.
Topics: Electrocardiography; Humans; Pacemaker, Artificial; Sick Sinus Syndrome
PubMed: 23939447
DOI: No ID Found -
Biological Psychology May 2023The polyvagal collection of hypotheses is based upon five essential premises, as stated by its author (Porges, 2011). Polyvagal conjectures rest on a primary assumption... (Review)
Review
The polyvagal collection of hypotheses is based upon five essential premises, as stated by its author (Porges, 2011). Polyvagal conjectures rest on a primary assumption that brainstem ventral and dorsal vagal regions in mammals each have their own unique mediating effects upon control of heart rate. The polyvagal hypotheses link these putative dorsal- vs. ventral-vagal differences to socioemotional behavior (e.g. defensive immobilization, and social affiliative behaviors, respectively), as well as to trends in the evolution of the vagus nerve (e.g. Porges, 2011 & 2021a). Additionally, it is essential to note that only one measurable phenomenon-as index of vagal processes-serves as the linchpin for virtually every premise. That phenomenon is respiratory sinus arrhythmia (RSA), heart-rate changes coordinated to phase of respiration (i.e. inspiration vs. expiration), often employed as an index of vagally, or parasympathetically, mediated control of heart rate. The polyvagal hypotheses assume that RSA is a mammalian phenomenon, since Porges (2011) states "RSA has not been observed in reptiles." I will here briefly document how each of these basic premises have been shown to be either untenable or highly implausible based on the available scientific literature. I will also argue that the polyvagal reliance upon RSA as equivalent to general vagal tone or even cardiac vagal tone is conceptually a category mistake (Ryle, 1949), confusing an approximate index (i.e. RSA) of a phenomenon (some general vagal process) with the phenomenon, itself.
Topics: Animals; Humans; Vagus Nerve; Heart; Arrhythmia, Sinus; Respiratory Sinus Arrhythmia; Respiration; Heart Rate; Mammals
PubMed: 37230290
DOI: 10.1016/j.biopsycho.2023.108589 -
Nature Communications Apr 2019Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm...
Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 μJ, which is higher than the required endocardial pacing threshold energy (0.377 μJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.
Topics: Animals; Arrhythmia, Sinus; Cardiac Surgical Procedures; Cell Line; Dimethylpolysiloxanes; Disease Models, Animal; Electrophysiological Phenomena; Equipment Design; Heart; Male; Mice; Nanomedicine; Nylons; Pacemaker, Artificial; Polytetrafluoroethylene; Prosthesis Implantation; Sus scrofa
PubMed: 31015519
DOI: 10.1038/s41467-019-09851-1 -
Cellular and Molecular Life Sciences :... Apr 2017The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome... (Review)
Review
The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development.
Topics: Arrhythmia, Sinus; Heart Diseases; Homeodomain Proteins; Humans; LIM-Homeodomain Proteins; Pacemaker, Artificial; Sinoatrial Node; T-Box Domain Proteins; Transcription Factors
PubMed: 27770149
DOI: 10.1007/s00018-016-2400-1 -
Circulation Research Dec 2020Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat....
RATIONALE
Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the -regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified.
OBJECTIVE
To define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.
METHODS AND RESULTS
We used ATAC-seq on sorted neonatal mouse SAN to compare regions of accessible chromatin in PCs and right atrial cardiomyocytes. PC-enriched assay for transposase-accessible chromatin peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of TF (transcription factor) binding sites. Among several novel SAN enhancers that were experimentally validated using transgenic mice, we identified a 2.9-kb regulatory element at the locus that was active specifically in the cardiac inflow at embryonic day 8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations.
CONCLUSIONS
(1) PCs have distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers, (2) -regulation of specifically in the SAN depends upon a conserved SAN enhancer that regulates PC development and SAN function, and (3) a corresponding human enhancer may regulate human SAN function.
Topics: Action Potentials; Animals; Arrhythmia, Sinus; Biological Clocks; Chromatin Immunoprecipitation Sequencing; Enhancer Elements, Genetic; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Gestational Age; Heart Rate; Humans; LIM-Homeodomain Proteins; Male; Mice, Inbred C57BL; Mice, Transgenic; Polymorphism, Single Nucleotide; Sinoatrial Node; Time Factors; Transcription Factors; Zebrafish
PubMed: 33044128
DOI: 10.1161/CIRCRESAHA.120.317145 -
Biological Psychology Feb 2024Linchpin to the entire area of psychophysiological research and discussion of the vagus is the respiratory and cardiovascular phenomenon known as respiratory sinus... (Review)
Review
Linchpin to the entire area of psychophysiological research and discussion of the vagus is the respiratory and cardiovascular phenomenon known as respiratory sinus arrhythmia (RSA; often synonymous with high-frequency heart-rate variability when it is specifically linked to respiratory frequency), i.e. rhythmic fluctuations in heart rate synchronized to inspiration and expiration. This article aims 1) to clarify concepts, terms and measures commonly employed during the last half century in the scientific literature, which relate vagal function to psychological processes and general aspects of health; and 2) to expand upon an earlier theoretical model, emphasizing the importance of RSA well beyond the current focus upon parasympathetic mechanisms. A close examination of RSA and its relations to the vagus may 1) dispel certain commonly held beliefs about associations between psychological functioning, RSA and the parasympathetic nervous system (for which the vagus nerve plays a major role), and 2) offer fresh perspectives about the likely functions and adaptive significance of RSA, as well as RSA's relationship to vagal control. RSA is neither an invariably reliable index of cardiac vagal tone nor of central vagal outflow to the heart. The model here presented posits that RSA represents an evolutionarily entrenched, cardiovascular and respiratory phenomenon that significantly contributes to meeting continuously changing metabolic, energy and behavioral demands.
Topics: Humans; Respiratory Sinus Arrhythmia; Vagus Nerve; Arrhythmia, Sinus; Heart; Parasympathetic Nervous System; Heart Rate
PubMed: 38151156
DOI: 10.1016/j.biopsycho.2023.108739 -
Biomedicine & Pharmacotherapy =... Aug 2023Sinus node dysfunction is a common arrhythmia disorder with a high incidence and significant social and economic burden. Currently, there are no effective drugs for... (Review)
Review
Sinus node dysfunction is a common arrhythmia disorder with a high incidence and significant social and economic burden. Currently, there are no effective drugs for treating chronic sinus node dysfunction. The disease is associated with ion channel disturbances caused by aging, fibrosis, inflammation, oxidative stress, and autonomic dysfunction. Natural active substances and Chinese herbal medicines have been widely used and extensively studied in the medical community for the treatment of arrhythmias. Multiple studies have demonstrated that various active ingredients and Chinese herbal medicines, such as astragaloside IV, quercetin, and ginsenosides, exhibit antioxidant effects, reduce fibrosis, and maintain ion channel stability, providing promising drugs for treating sinus node dysfunction. This article summarizes the research progress on natural active ingredients and Chinese herbal formulas that regulate sick sinoatrial node function, providing valuable references for the treatment of sinus node dysfunction.
Topics: Humans; Sick Sinus Syndrome; Sinoatrial Node; Arrhythmias, Cardiac; Aging; Plant Extracts
PubMed: 37229801
DOI: 10.1016/j.biopha.2023.114777 -
Annual Review of Pharmacology and... Jan 2021The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the... (Review)
Review
The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the heart's inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. However, other forms of SND exist, including idiopathic primary SND, which is genetic, and forms that are secondary to cardiovascular or systemic disease. The incidence of SND in the general population is expected to increase over the next half century, boosting the need to implant electronic pacemakers. During the last two decades, our knowledge of sino-atrial node physiology and of the pathophysiological mechanisms underlying SND has advanced considerably. This review summarizes the current knowledge about SND mechanisms and discusses the possibility of introducing new pharmacologic therapies for treating SND.
Topics: Heart Conduction System; Humans; Sick Sinus Syndrome; Sinoatrial Node
PubMed: 33017571
DOI: 10.1146/annurev-pharmtox-031120-115815