Materiały źródłowe

• #1 Overview of Basic Mechanisms of Cardiac Arrhythmia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3164530/

  A cardiac arrhythmia simply defined is a variation from the normal heart rate and/or rhythm that is not physiologically justified. Recent years have witnessed important advances in our understanding of the electrophysiologic mechanisms underlying the development of a variety of cardiac arrhythmias. The mechanisms responsible for cardiac arrhythmias are generally divided into 2 major categories: (1) enhanced or abnormal impulse formation (ie, focal activity) and (2) conduction disturbances (ie, reentry). […] Abnormal automaticity includes both reduced automaticity, which causes bradycardia, and increased automaticity, which causes tachycardia. Arrhythmias caused by abnormal automaticity can result from diverse mechanisms. Alterations in sinus rate can be accompanied by shifts of the origin of the dominant pacemaker within the sinus node or to subsidiary pacemaker sites elsewhere in the atria. Impulse conduction out of the SA mode can be impaired or blocked as a result of disease or increased vagal activity leading to development of bradycardia. AV junctional rhythms occur when AV junctional pacemakers located either in the AV node or in the His bundle accelerate to exceed the rate of SA node, or when the SA nodal activation rate was too slow to suppress the AV junctional pacemaker.

• #2 Mechanisms of cardiac arrhythmias

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4823581/

  Blood circulation is the result of the beating of the heart, which provides the mechanical force to pump oxygenated blood to, and deoxygenated blood away from, the peripheral tissues. This depends critically on the preceding electrical activation. Disruptions in the orderly pattern of this propagating cardiac excitation wave can lead to arrhythmias. Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cardiac action potential, which is discussed in the first part of this review. […] Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cellular action potential, which is discussed in the first part of this review. A brief outline of the different classification systems of arrhythmogenesis is then provided, followed by a discussion of each mechanism in turn, highlighting recent advances in this area.

• #2 Overview of Basic Mechanisms of Cardiac Arrhythmia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3164530/

  Bradycardia can occur in structurally normal hearts because of genetic mutations that result in abnormalities of either membrane clock or Ca clock mechanisms of automaticity. One example is the mutation of hyperpolarization-activated nucleotide-gated channel (HCN4), which is part of the channels that carry If. Mutations of the HCN4 may cause familial bradycardia as well. […] Common diseases, such as heart failure and atrial fibrillation, may be associated with significant SA node dysfunction. Malfunction of both membrane voltage and Ca clocks might be associated with both of these common diseases. Zicha and colleagues reported that down-regulation of HCN4 expression contributes to heart failure-induced sinus node dysfunction. […] Atrial and ventricular myocardial cells do not display spontaneous diastolic depolarization or automaticity under normal conditions, but can develop these characteristics when depolarized, resulting in the development of repetitive impulse initiation, a phenomenon termed depolarization-induced automaticity. The membrane potential at which abnormal automaticity develops ranges between 70 and 30 mV. The rate of abnormal automaticity is substantially higher than that of normal automaticity and is a sensitive function of resting membrane potential.

• #3 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-of-cardiac-arrhythmias-articulo-S1885585711006086

  Cardiac arrhythmias are prevalent among humans across all age ranges and may occur in the setting of underlying heart disease as well as in structurally normal hearts. While arrhythmias are widely varied in their clinical presentations, they possess shared electrophysiologic properties at the cellular level. The 3 main mechanisms responsible for cardiac arrhythmias are automaticity, triggered activity, and reentry. Although identifying the specific mechanism may at times be challenging for the clinician and require invasive electrophysiologic study, differentiating and understanding the underlying mechanism may be critical to the development of an appropriate diagnosis and treatment strategy. […] Understanding the mechanisms of arrhythmias is helpful to the appropriate management and treatment of all arrhythmia types. Since the mechanisms that lead to clinical arrhythmias are frequently due to abnormalities beyond the tissue level, it is also essential to understand what occurs at the cellular level.

• #4 Electrophysiological Mechanisms of Cardiac Arrhythmias | Thoracic Key

  https://thoracickey.com/electrophysiological-mechanisms-of-cardiac-arrhythmias/

  Automaticity is the property of cardiac cells to initiate an impulse spontaneously, without need for prior stimulation. […] Reentry is the likely mechanism of most recurrent clinical arrhythmias. […] The mechanisms responsible for cardiac arrhythmias are generally divided into categories of disorders of impulse formation (automaticity or triggered activity), disorders of impulse conduction (reentry), or combinations of both. […] Diagnosis of the underlying mechanism of an arrhythmia can be of great importance in guiding appropriate treatment strategies. […] However, our present diagnostic tools do not always permit unequivocal determination of the electrophysiological mechanisms responsible for many clinical arrhythmias or their ionic bases. […] This is further complicated by the fact that some arrhythmias can be started by one mechanism and perpetuated by another.

• #5 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-of-cardiac-arrhythmias-articulo-S1885585711006086

  The mechanisms responsible for cardiac arrhythmias may be divided into disorders of impulse formation, disorders of impulse conduction or a combination of both. […] As described previously, some specialized heart cells, such as sinoatrial nodal cells, the atrioventricular (AV) node, and the His-Purkinje system, as well as some cells in both atria, possess the property of pacemaker activity or automaticity. Suppression or enhancement of this activity may lead to clinical arrhythmias. […] Pacemaker activity is controlled by the autonomic nervous system and can be modulated by a variety of systemic factors, including metabolic abnormalities and endogenous or pharmacologic substances. […] The hallmark of normal automaticity is overdrive suppression. Overdriving a latent pacemaker cell faster than its intrinsic rate decreases the slope of phase 4, mediated mostly by enhanced activity of the Na/K exchange pump.

• #6 Mechanisms of cardiac arrhythmias

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4823581/

  Several schemes have been used to classify the mechanisms of cardiac arrhythmias. Traditionally, these have been divided into nonreentrant and reentrant activity. An alternative scheme divided them into those occurring at the cellular and tissue levels. A dynamics-based classification, focusing on the trigger-tissue substrate interactions, divided arrhythmogenic mechanisms into unstable calcium cycling, reduced repolarization reserve, and excess repolarization reserve. […] Triggered activity results from the premature activation of cardiac tissues by afterdepolarizations, which are depolarizations triggered by one or more preceding action potentials. […] Early afterdepolarizations (EADs) can develop before full repolarization, corresponding to phase 2 or phase 3 of the cardiac action potential in humans. They are usually but not exclusively associated with prolonged action potential durations (APDs), which occur when the inward current is greater in amplitude than the outward current.

• #7 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-of-cardiac-arrhythmias-articulo-S1885585711006086

  Abnormal automaticity is thought to play a role in cases of elevated extracellular potassium, low intracellular pH, and catecholamine excess. […] Triggered activity (TA) is defined by impulse initiation caused by afterdepolarizations (membrane potential oscillations that occur during or immediately following a preceding AP). […] Delayed Afterdepolarization-Induced Triggered Activity is an oscillation in membrane voltage that occurs after completion of repolarization of the AP (during phase 4). […] Early afterdepolarization-triggered arrhythmias are rate dependent, and in general the EAD amplitude increases at a slow rate. […] Reentry has been divided in 2 main groups: anatomical or classic reentry, where the circuit is determined by anatomical structures, and functional reentry, which in turn includes different mechanisms.

• #8 Overview of Basic Mechanisms of Cardiac Arrhythmia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3164530/

  EADs are typically observed in cardiac tissues exposed to injury, altered electrolytes, hypoxia, acidosis, catecholamines, and pharmacologic agents, including antiarrhythmic drugs. Ventricular hypertrophy and heart failure also predispose to the development of EADs. EAD characteristics vary as a function of animal species, tissue or cell type, and the method by which the EAD is elicited. […] An example of DAD-induced arrhythmia is the catecholaminergic polymorphic ventricular tachycardia (CPVT), which may be caused by the mutation of either the type 2 ryanodine receptor (RyR2) or the calsequestrin (CSQ2). The principal mechanism underlying these arrhythmias is the leaky ryanodine receptor, which is aggravated during catecholamine stimulation. […] In 2003, Burashnikov and Antzelevitch described a novel mechanism giving rise to triggered activity, termed late phase 3 EAD, which combines properties of both EAD and DAD, but has its own unique character. Late phase 3 EAD-induced triggered extrasystoles represent a new concept of arrhythmogenesis in which abbreviated repolarization permits normal SR calcium release to induce an EAD-mediated closely coupled triggered response, particularly under conditions permitting intracellular calcium loading.

• #9 Mechanisms of cardiac arrhythmias

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4823581/

  Delayed afterdepolarizations (DADs) were first described as oscillatory afterpotentials. They can develop after full repolarization, corresponding to phase 4 of the cardiac action potential in humans. DADs are observed under conditions of intracellular calcium overload, which can result from exposure to digitalis, catecholamines, hypokalemia, and hypercalcemia, and in hypertrophy and heart failure. […] Re-entry occurs when an action potential fails to extinguish itself and reactivates a region that has recovered from refractoriness. It can be divided into two types: (i) reentry that occurs in the presence of an obstacle, around which an action potential can travel (circus-type); and (ii) reentry that occurs without an obstacle (reflection or phase 2). […] Phase 2 reentry is another mechanism that does not depend on circus-type movement. Its concept emerged from experiments that introduced pinacidil, an activator of the ATP-regulated potassium current, IK,ATP, to canine ventricular tissues. The canine ventricular action potentials have a spike and dome morphology. […] The concept of prolonged repolarization-dependent reexcitation (PRDR) proposed earlier is also similar to that of phase 2 reentry. PRDR requires an area of myocardium with prolonged repolarization connected to another area with a normal repolarization time-course.

• #10 Overview of Basic Mechanisms of Cardiac Arrhythmia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3164530/

  Reentry is fundamentally different from automaticity or triggered activity in the mechanism by which it initiates and sustains cardiac arrhythmias. Circus movement reentry occurs when an activation wavefront propagates around an anatomic or functional obstacle or core, and reexcites the site of origin. […] The mechanisms of arrhythmogenesis in BrS can be explained by the heterogeneous shortening of the APD on the right ventricular epicardium.

• #11 Overview of Arrhythmias – Cardiovascular Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/cardiovascular-disorders/overview-of-arrhythmias-and-conduction-disorders/overview-of-arrhythmias

  Rhythm disturbances result from abnormalities of impulse formation, impulse conduction, or both. […] Bradyarrhythmias result from decreased intrinsic pacemaker function or blocks in conduction, principally within the AV node or the His-Purkinje system. […] Most tachyarrhythmias are caused by reentry; some result from enhanced normal automaticity or from abnormal mechanisms of automaticity. […] Reentry is the circular propagation of an impulse around 2 interconnected pathways with different conduction characteristics and refractory periods. […] Under certain conditions, typically precipitated by a premature beat, reentry can cause continuous circulation of an activation wavefront, causing a tachyarrhythmia. […] However, 3 conditions favor reentry: Shortening of tissue refractoriness (eg, by sympathetic stimulation), Lengthening of the conduction pathway (eg, by hypertrophy or abnormal conduction pathways), Slowing of impulse conduction (eg, by ischemia).

• #12 IJMS | Special Issue : Pathogenesis of Cardiac Arrhythmias and Heart Failure

  https://www.mdpi.com/journal/ijms/special_issues/cardiac_arrhythmias

  Pathogenesis of Cardiac Arrhythmias and Heart Failure […] Cardiac arrhythmias are any of a group of conditions in which the electrical activity of the heart is irregular or is faster or slower than normal. Up to 50% of patients die suddenly at the first manifestation of cardiac diseases; the majority of these patients die of ventricular fibrillation, a lethal cardiac arrhythmia. Heart failure, a syndrome characterized by inadequate systemic perfusion owing to reduced cardiac pumping, is the most common cause of hospitalization of cardiovascular diseases and imposes a great burden on the healthcare system and society. […] Cardiac arrhythmias and heart failure are usually interwoven and react with each other; they have been a prevailing public health problem among humans across all ages. Understanding the pathogenesis of cardiac arrhythmias and heart failure is critical to the development of diagnostic, treatment and preventive strategies. The current understanding of electrophysiological mechanisms of cardiac arrhythmias includes automaticity, triggered activity and reentry, and an understanding of pathogenetic mechanisms of heart failure includes a multitude of biomechanical, hemodynamic, hormonal and pathologic stimuli. However, the molecular pathways of cardiac arrhythmias and heart failure are still elusive, and novel molecular defects and pathways remain to be identified for screening, molecular diagnosis, drug-target development, and personalized medicine.

• #13

  https://journals.lww.com/cardiologyinreview/fulltext/2025/05000/mechanism_of_ion_channel_impairment_in_the.12.aspx

  Sudden cardiac death is the most unpredictable and devastating consequence of hypertrophic cardiomyopathy, most often caused by persistent ventricular tachycardia or ventricular fibrillation. […] the cardiomyocyte mechanism based on ion channel abnormalities may play an important role in the early stages of the disease. […] In recent years, research on ion channels in arrhythmias in HCM patients has drawn increasing attention to the role of ion channel impairment in the occurrence of arrhythmias in HCM patients. […] Evidence has shown that nearly every AP-related current is abnormal in HCM cardiomyocytes with electrophysiological impairments, resulting in significant abnormalities in AP dynamics and duration. […] The increased ionic current causes intracellular Na+ and Ca2+ concentrations to be higher than those in the control group via several complex mechanisms, resulting in an increased frequency of EADs or delayed after depolarizations and thus induced arrhythmias.

• #14

  https://journals.lww.com/cardiologyinreview/fulltext/2025/05000/mechanism_of_ion_channel_impairment_in_the.12.aspx

  Notably, the extent of APD prolongation in cardiomyocytes from HCM patients is independent of the presence and location of muscle cell mutations. […] This observation suggests that the prolongation of APD is not the direct result of the induced mutation but rather the result of a complex hypertrophic remodeling process involving multiple signaling pathways and genetic modifications. […] CaMKII-induced increased ion channel phosphorylation results in increased intracellular Na+ and Ca2+ levels, which is an electrophysiological abnormality event at the cellular level. […] The occurrence of arrhythmias in HCM patients is driven by functional alterations at the cellular and molecular levels, which may be a new target for innovative treatments.

• #15 Breakthrough in arrhythmia mechanism

  https://www.medscape.com/viewarticle/784250

  Reduced activity in the cardiac sodium channel appears to be responsible for several conduction defects that can cause various arrhythmias, a new study in mice shows. […] These findings provide a background for understanding the pathophysiology of several clinical conditions such as isolated cardiac conduction disease, progressive cardiac conduction disorder, and idiopathic ventricular fibrillation, the authors, mostly from the University of Cambridge, UK, write. „These results taken together with those obtained from computer modeling and clinical observations suggest that slow conduction as a result of sodium channel dysfunction represents a critical target for understanding and managing cardiac arrhythmias,” they conclude. […] He said the findings could also explain the negative results of the CAST study with Class I antiarrhythmics which slow sodium conduction.

• #16 Mechanism discovered that leads to cardiac arrhythmias in heart failure

  https://dzhk.de/en/newsroom/news/latest-news/article/mechanism-discovered-that-leads-to-cardiac-arrhythmias-in-heart-failure

  Mechanism discovered that leads to cardiac arrhythmias in heart failure. Scientists have uncovered a mechanism that leads to arrhythmias. The disturbed heartbeat results mainly from sodium channels closing late in these patients. The late flow of sodium disrupts the sequence of electrophysiological and biochemical processes, and cardiac arrhythmias can result. DZHK scientists from the Heart Centre Gttingen have proved in many experiments that a specific sodium channel, which is actually assigned to the nervous system, occurs more frequently in the heart muscle cells during cardiac insufficiency. This sodium channel NaV1.8 and a particular protein, which plays a central role in the development of cardiac insufficiency, influence each other so that the sodium current increases dramatically. […] In these cells, the sodium channel Nav1.8 was cut out using the CRISPR-Cas9 gene scissors. In the cells modified in this way, we could stop the late sodium current. So we proved that Nav1.8 is involved in the late sodium current. […] In the mouse model, there were also fewer cardiac arrhythmias after Nav1.8 was switched off. This also improved the survival of the mice. We hope that this is indeed an effective therapeutic approach for arrhythmias.

• #17 Electrolyte’s imbalance role in atrial fibrillation: Pharmacological management | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-022-00065-z

  The contribution of the perpetuation of atrial fibrillation is caused by electrical remodeling in which calcium, sodium and potassium channels could refer to changes in the ion channel protein expression, development of fibrosis, gene transcription and ion channel redistribution. […] Calcium and magnesium could influence the risk of atrial fibrillation which is the leading cause of cardiac death, heart failure and ischemic stroke. […] The elevated serum concentration of calcium had a higher range of in-patients mortality, increased total cost of hospitalization and increased length of hospital stay as compared to those without hypercalcemia in atrial fibrillation patients. […] Moreover, chloride channels could affect homeostasis, atrial myocardial metabolism which may participate in the development of atrial fibrillation.

• #18 Electrolyte’s imbalance role in atrial fibrillation: Pharmacological management | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-022-00065-z

  Up to a 50% risk of incidence of AF are higher in which left ventricular hypertrophy, sudden cardiovascular death and overall mortality relate to a low serum magnesium level. […] Additionally, magnesium prevents the occurrence of AF after cardiac surgery, whereas greater levels of serum phosphorus in the large population-based study and the related calciumphosphorus products were linked with a greater incidence of AF. […] Numerous clinical studies had shown the high preoperative risk of AF that is linked with lower serum potassium levels. […] The conventional risk factor of increased risk of new onset of AF events could independently link with high dietary sodium intake which enhances the fibrosis and inflammation in the atrium but the mechanism remains unknown. […] This review concludes that electrolytes imbalance plays a significant role in the pathogenesis of atrial fibrillation.

• #19 Inflammation and arrhythmogenesis: a narrative review of the complex relationship | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-024-00110-z

  A biological mechanism called inflammation is necessary for reacting to damaging stimuli, but it can also, ironically, play a role in the formation of arrhythmias, or the group of disorders known as arrhythmogenesis. […] Through oxidative stress, autonomic dysfunction, electrolyte imbalances, and coagulation activation, systemic inflammation may impact arrhythmogenicity. […] Similar to neuropathic alterations, direct cellular damage, and structural remodeling, localized heart inflammation also predisposes to arrhythmias. […] Studies demonstrating the impact of cytokines on ion channel expression and function, along with clinical associations between inflammatory indicators and arrhythmia incidence, offer the molecular insights. […] Immune cells like macrophages that alter cardiac conduction are involved in the interaction between inflammation and electrophysiology, which further complicates the situation.

• #20 Inflammation and arrhythmogenesis: a narrative review of the complex relationship | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-024-00110-z

  Arrhythmogenesis and inflammation are inherently linked by a number of mechanisms that change the electrical characteristics of the heart. […] Arrhythmias can be initiated or exacerbated by inflammation, which can change the electrophysiological properties of cardiac cells, such as ion channel expression, membrane potential, calcium handling, and gap junction coupling. […] Apoptosis, hypertrophy, and fibrosis are examples of structural changes that inflammation may cause in cardiac tissue. […] On the other hand, arrhythmias may cause or worsen inflammation by injuring the heart through mechanical strain, ischemia-reperfusion, or oxidative stress. […] The aim of this narrative review is to clarify the intricate connection between inflammation and arrhythmogenesis, highlighting the numerous ways that both localized and systemic inflammation can affect the onset and course of different cardiac arrhythmias.

• #21 Inflammation and arrhythmogenesis: a narrative review of the complex relationship | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-024-00110-z

  First, oxidative stress and cardiac cell damage from systemic inflammation might result in decreased electrical conduction and heightened vulnerability to reentry circuits. […] Second, the autonomic nervous system (ANS) might have its equilibrium upset by systemic inflammation. […] Third, since potassium, calcium, and magnesium are necessary for a proper ventricular action potential, systemic inflammation may have an impact on these electrolyte levels. […] Fourth, systemic inflammation has the potential to trigger the coagulation system and raise the risk of thromboembolism, both of which can result in myocardial infarction and ischemia. […] Specific infections include bacterial, fungal, or viral infections as well as autoimmune disorders can result in localized inflammation. […] First, there is a chance that localized inflammation will cause structural remodeling in cardiovascular tissue, in addition to processes like necrosis, apoptosis, and fibrosis.

• #22 Inflammation and arrhythmogenesis: a narrative review of the complex relationship | International Journal of Arrhythmia | Full Text

  https://arrhythmia.biomedcentral.com/articles/10.1186/s42444-024-00110-z

  Second, localized inflammation may result in inflammation of the ganglia or cardiac nerves, which may change how the heart’s autonomic nervous system regulates itself. […] Third, localized inflammation may directly harm the heart’s cells, impairing their ability to handle calcium, boosting their automaticity, or making them more susceptible to catecholamines. […] Fourth, localized inflammation may compress or infiltrate the cardiac conduction system, including the His-Purkinje system, the atrioventricular node, and the sinoatrial node, which may result in heart block or bradyarrhythmias. […] The review has also brought attention to the crucial role that immune cells – particularly macrophages – play in regulating the heart’s electrical characteristics, offering fresh perspectives on the cellular and molecular mechanisms that support the link between inflammation and irregular heartbeats. […] It emphasized the importance of cytokine profile disruptions, including IL-1, TNF-, and IL-6, which can modify cardiac ion channel function and connexin expression, which in turn shapes the ventricular action potential and increases the risk of arrhythmia.

• #23 Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism | Scientific Reports

  https://www.nature.com/articles/srep20835

  Myocardial fibrosis is an important risk factor for cardiac arrhythmias. […] We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. […] Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. […] The relation of fibrosis and arrhythmias has been investigated in several experimental studies. […] It has been shown that the inducibility of ventricular arrhythmias increases in a nearly linear fashion with the amount of fibrosis. […] Studies have shown that the structure and spatial distribution of fibrosis play a crucial role in arrhythmogenesis. […] A more detailed study revealed that not only the inducibility of arrhythmia, but also period of activation is determined by the highest level of local fibrosis.

• #24 Arrhythmias in Cardiac Amyloidosis

  https://www.innovationsincrm.com/cardiac-rhythm-management/articles-2018/march/1179-arrhythmias-in-cardiac-amyloidosis

  The conduction system is affected in all forms of CA. Atrioventricular (AV) conduction delay or block is more common than sinus node disease: despite the high frequency of atrial involvement with amyloidosis, sinus node disease appears to be less common and relevant reports are mostly limited to isolated events in patients with ATTRm. […] Approximately 25% to 35% of ATTRm and 45% of ATTRwt patients receive pacemaker implants. While cardiac pacing provides symptomatic relief, it does not change the overall prognosis. […] Atrial fibrillation (AF) or atrial tachycardia (AT) is common in CA, especially as the disease progresses. […] AF in amyloidosis tends to have longer cycle lengths and may appear organized. This is likely due to amyloid deposition separating out the atrial myocyte bundles and creating a marked delay in intra-atrial conduction.

• #25 Arrhythmias in Cardiac Amyloidosis

  https://www.innovationsincrm.com/cardiac-rhythm-management/articles-2018/march/1179-arrhythmias-in-cardiac-amyloidosis

  Arrhythmias are common in cardiac amyloidosis and vary based on the amyloidosis type. Conduction defects and atrial arrhythmias are more prevalent in transthyretin amyloidosis compared with light chain amyloidosis, and this difference might be a reflection of the longer survival time in the former. […] Cardiac involvement is invariable in ATTRwt. In the familial TRR amyloidoses (ie, ATTRm), the prevalence of CA varies with the specific mutation. AL amyloidosis may have minimal or severe cardiac involvement, with 50% of patients showing CA. Regardless of the cause of amyloid production, CA is characterized by extracellular amyloid deposition throughout the heart, including the cardiac conduction tissue and valves. The ventricles are non-dilated and thickened, with restrictive filling. Elevated filling pressures result in atrial dilation despite atrial wall thickening from amyloid deposition. Atrial arrhythmias and loss of atrial mechanical function with atrial thrombus formation are important risk factors for cardioembolic stroke.

• #26 Arrhythmias in Cardiac Amyloidosis

  https://www.innovationsincrm.com/cardiac-rhythm-management/articles-2018/march/1179-arrhythmias-in-cardiac-amyloidosis

  The histology of CA is amyloid infiltration of the extracellular spaces separating and distorting the myocardial cells. Myocardial scarring and patchy fibrosis that are typical of chronic ischemic cardiomyopathy or other non-ischemic cardiomyopathies are not described in CA. Hence, the exact mechanism of arrhythmias in CA is less well defined and is likely to be multifactorial. Small vessel disease due to perivascular amyloid infiltration associated with impaired vasodilation is a likely substrate for myocardial ischemia, especially in AL. […] Inflammatory cell damage and separation of myocytes by amyloid fibrils would explain conduction abnormalities, atrial arrhythmias, and loss of atrial contractility. In the ventricles, non-sustained ventricular tachycardia (VT) is the most common form of arrhythmia. Sustained monomorphic VT is uncommon, as most unexpected lethal ventricular arrhythmias are due to polymorphic VT or ventricular fibrillation.

• #27 Molecular mechanism for an inherited cardiac arrhythmia | Nature

  https://www.nature.com/articles/376683a0

  IN the congenital long-QT syndrome, prolongation of the cardiac action potential occurs by an unknown mechanism and predisposes individuals to syncope and sudden death as a result of ventricular arrhythmias. […] Persistent inward sodium current explains prolongation of cardiac action potentials, and provides a molecular mechanism for this form of congenital long-QT syndrome.

• #28 Atrial fibrillation – Wikipedia

  https://en.wikipedia.org/wiki/Atrial_fibrillation

  Atrial fibrillation is associated with an increased risk of heart failure, dementia, and stroke. […] Atrial fibrillation frequently results from bursts of tachycardia that originate in muscle bundles extending from the atrium to the pulmonary veins. […] The ganglionated plexi (autonomic ganglia of the heart atrium and ventricles) can also be a source of atrial fibrillation, and are sometimes also ablated for that reason. […] As atrial fibrillation becomes more persistent, the junction between the pulmonary veins and the left atrium becomes less of an initiator and the left atrium becomes an independent source of arrhythmias. […] Cortisol and other stress biomarkers, as well as emotional stress, may play a role in the pathogenesis of atrial fibrillation. […] The primary pathologic change seen in atrial fibrillation is the progressive fibrosis of the atria.

• #29 Atrial fibrillation – Wikipedia

  https://en.wikipedia.org/wiki/Atrial_fibrillation

  Once dilation of the atria has occurred, this begins a chain of events that leads to the activation of the reninangiotensinaldosterone system (RAAS) and subsequent increase in the matrix metalloproteinases and disintegrin, which leads to atrial remodeling and fibrosis, with loss of atrial muscle mass. […] Along with fibrosis, alterations in the atria that predispose to atrial fibrillation affect their electrical properties, as well as their responsiveness to the autonomic nervous system. […] An important theory is that the regular impulses produced by the sinus node for a normal heartbeat are overwhelmed by rapid electrical discharges produced in the atria and adjacent parts of the pulmonary veins. […] In a heart with AF, the increased calcium release from the sarcoplasmic reticulum and increased calcium sensitivity can lead to an accumulation of intracellular calcium and causes downregulation of L-type calcium channels. […] The abnormal distribution of gap junction proteins such as GJA1 (also known as connexin 43), and GJA5 (connexin 40) causes non-uniformity of electrical conduction, thus causing the arrhythmia.

• #30 Atrial Arrhythmias in Pulmonary Hypertension: Pathogenesis, Prognosis and Management | AER Journal

  https://www.aerjournal.com/articles/atrial-arrhythmias-pulmonary-hypertension-pathogenesis-prognosis-and-management?language_content_entity=en

  Atrial arrhythmias, including atrial fibrillation and atrial flutter, are common in patients with pulmonary hypertension and are closely associated with clinical decompensation and poor clinical outcomes. The mechanisms of arrhythmogenesis and subsequent clinical decompensation are reviewed. Practical implications and current evidence for the management of atrial arrhythmias in patients with pulmonary hypertension are summarised. […] The altered structural and electrophysiological properties of the left atrium in the setting of AF and left heart disease have been well described. In PH, enlargement of the right atrium (RA) is thought to reflect advancing disease and potential progression to right heart failure as elevated pulmonary and right ventricular pressures are transmitted to the RA. Observational studies suggest that RA pressure and chamber size are important risk factors for atrial arrhythmia development. Chronic RA pressure overload and stretching, along with chronic hypoxia, may alter the atrial substrate by promoting fibrosis and local tissue heterogeneities, which in turn predispose to a risk for AF. This is consistent with emerging data demonstrating a key role of atrial fibrosis in the pathogenesis of AF as documented by delayed enhancement on MRI.

• #31 Atrial Arrhythmias in Pulmonary Hypertension: Pathogenesis, Prognosis and Management | AER Journal

  https://www.aerjournal.com/articles/atrial-arrhythmias-pulmonary-hypertension-pathogenesis-prognosis-and-management?language_content_entity=en

  Electrophysiologic studies (EPSs) in patients with idiopathic PAH compared with control patients without PH demonstrate reproducible and quantifiable abnormalities in atrial conduction. In a study by Medi et al., EPSs were performed in eight patients with idiopathic PAH prior to starting PH therapies and the results were compared with those from 16 age-matched controls without PH undergoing EPS for supraventricular tachycardia. The group with PAH had slower conduction velocities throughout the RA and a significant generalised voltage reduction consistent with the presence of atrial fibrosis. In addition, patients with PAH were found to have higher rates of AF inducibility (50 % versus 0 % in controls), defined as sustained AF 30 seconds. […] The development of AF is considered an independent predictor of adverse outcomes in various cardiac conditions including heart failure with reduced or preserved ejection fraction, valvular disease, and hypertrophic cardiomyopathy. AF may be a marker of advanced disease or decompensated cardiac substrate, but it can also contribute to disease progression and exacerbation. Both are likely true in patients with PH.

• #32 Atrial Arrhythmias in Pulmonary Hypertension: Pathogenesis, Prognosis and Management | AER Journal

  https://www.aerjournal.com/articles/atrial-arrhythmias-pulmonary-hypertension-pathogenesis-prognosis-and-management?language_content_entity=en

  Multiple mechanisms may account for the clinical deterioration seen in PH patients who develop atrial arrhythmias. The negative effect on cardiac output from the loss of atrial contraction, loss of atrioventricular synchrony, and ventricular irregularity has been described in patients with atrial arrhythmia and left heart failure. These effects may be particularly severe for patients with established right ventricular dysfunction or clinical right heart failure as a result of long-term PH.

• #33 Neurology and Cardiac Arrhythmias | ClinMed International Library | International Journal of Neurology and Neurotherapy |

  https://clinmedjournals.org/articles/ijnn/international-journal-of-neurology-and-neurotherapy-ijnn-3-051.php?jid=ijnn

  The imbalance of cardiac autonomic nervous system (CANS) is one of the major causes of cardiac arrhythmias and several novel therapies of arrhythmias through modulating the activity of CANS have emerged. […] It is well known that CANS plays a critical role in regulating the functions of the heart and its imbalance is regarded as one of the major causes of cardiac arrhythmias. […] A host of studies on the cardiac innervation have found a complex link known as cardiac autonomic nervous system (CANS), connecting extracardiac nerves, intracardiac ganglia, and myocardial cells. […] The interaction between ECNS and AF has been approved by several studies. […] The participation of CANS in the genesis of non-inherited ventricular tachyarrhythmias (VT) has been observed in several studies, most with elevated sympathetic activity that could reduce the ventricular fibrillation (VF) threshold and provoke VT.

• #34 Neurology and Cardiac Arrhythmias | ClinMed International Library | International Journal of Neurology and Neurotherapy |

  https://clinmedjournals.org/articles/ijnn/international-journal-of-neurology-and-neurotherapy-ijnn-3-051.php?jid=ijnn

  For the patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome (LQTS), the occurrences of VT are often precipitated by increased sympathetic activity and could be prevented by beta-blockage. […] Comprehensive studies on the characteristics and mechanism of cardiac autonomic nervous system in initiating and maintaining arrhythmias have brought out several novel therapeutic approaches to arrhythmias.

• #35 Arrhythmias and Heart Rate: Mechanisms and Significance of a Relationship | AER Journal

  https://www.aerjournal.com/articles/arrhythmias-and-heart-rate-mechanisms-and-significance-relationship?language_content_entity=en

  The occurrence of arrhythmia is often related to basic heart rate. […] The incidence of ventricular arrhythmias is often related, within an individual, to the rate of their underlying sinus rhythm (heart rate). […] The purpose of this short review is to discuss how arrhythmogenesis, by its diverse mechanisms, can be affected by heart rate. […] Heart rate, by itself, has important consequences for at least three factors relevant to electrical stability: the pattern of membrane current expression during the action potential; intracellular Ca2+ dynamics; and cellular energetic competence. […] Membrane current response to tachycardia is mostly relevant to repolarisation and is normally characterised by a net increment of outward (repolarising) current. […] Bradycardia prolongs repolarisation, on the other hand.

• #36 Arrhythmias and Heart Rate: Mechanisms and Significance of a Relationship | AER Journal

  https://www.aerjournal.com/articles/arrhythmias-and-heart-rate-mechanisms-and-significance-relationship?language_content_entity=en

  Overall, changes of membrane current expression during the action potential are such as to confer electrical stability in the case of tachycardia, but much less during bradycardia. […] Heart rate has profound effects on intracellular Ca2+ dynamics, which contribute to adapt contractility to the changes in cycle duration. […] Intracellular Ca2+ dynamics are relevant to arrhythmogenesis because cytosolic Ca2+ talks to membrane potential through Ca2+ sensitive mechanisms. […] Heart rate is the major determinant of oxygen consumption by both chemical (mainly Na+ and Ca2+ pumping) and mechanical (sarcomere shortening) components of cardiac work. […] In light of the arguments above, whereas tachycardia may afford greater electrical stability in the normal heart, it may well be an arrhythmia trigger when an abnormal substrate is present.

• #37 Arrhythmias and Heart Rate: Mechanisms and Significance of a Relationship | AER Journal

  https://www.aerjournal.com/articles/arrhythmias-and-heart-rate-mechanisms-and-significance-relationship?language_content_entity=en

  A substantial body of evidence indicates that, contrary to the view above, pronounced bradycardia may also facilitate life-threatening arrhythmias, as predicted by its destabilising effect on repolarisation. […] Therefore, as in the case of tachycardia-induced arrhythmias, arrhythmia ensuing during bradycardia may indicate the presence of a substrate, represented in this case by reduced repolarisation reserve. […] The concept of „inadequate rate response” introduces a quantitative argument in the discussion of the correlation between heart rate and arrhythmias. […] With the exception of parasystolic rhythm, in which appearance at slow rates is likely due to relief from overdrive suppression of an automatic focus, attribution of prognostic significance to arrhythmia relationship with heart rate should carefully consider the substrate likely present in the individual patient.

• #38 Pathological basis of cardiac arrhythmias: vicious cycle of immune-metabolic dysregulation

  https://www.oatext.com/pathological-basis-of-cardiac-arrhythmias-vicious-cycle-of-immune-metabolic-dysregulation.php

  Cardiac arrhythmias are a major type of cardiovascular diseases and account for high morbidity and mortality. The occurrence of cardiac arrhythmias is closely associated with abnormal neurohumoral regulation of heart rhythmicity and the pathogenesis of many cardiovascular diseases, particularly coronary artery disease (CAD). […] In this review, we highlight the mechanisms underlying arrhythmias, specifically involving disorders in immuno-metabolic network and the underlying signaling process. […] In the pathogenesis of these CVDs, immunologic injury and metabolic disorders are essential factors that constitute the immunometabolic basis of cardiac arrhythmias. […] The immunopathogenesis of cardiac rhythm and conduction disorders have been identified in sick sinus syndrome, bradyarrhythmias, and hypersensitive carotid sinus syndrome. […] These facts support the proposal that autoimmunity and inflammation take part in electrical and structural remodeling of left atrium and predispose patients with autoimmune and inflammatory diseases to increased risk of arrhythmia.

• #39 Pathological basis of cardiac arrhythmias: vicious cycle of immune-metabolic dysregulation

  https://www.oatext.com/pathological-basis-of-cardiac-arrhythmias-vicious-cycle-of-immune-metabolic-dysregulation.php

  Normal metabolism of the cardiovascular system is the prerequisite of normal HR. Varieties of metabolic disorders such as high triglyceride, low high-density lipoprotein and obesity as well as high or low plasma glucose levels and diabetes are associated with increased risk of atherosclerosis, CAD and the resultant arrhythmias. […] Dyslipidemia in association with abnormal amounts of cholesterol, triglycerides and unsaturated fatty acids in blood increases risk of arrhythmias. […] These facts indicate that dyslipidemia predisposes arrhythmias through cardiac lipotoxicity. […] In the pathogenesis of CVDs and the resultant arrhythmias, immunologic injuries and metabolic disorders occur simultaneously and are intertwined to form a malfunctioned immunometabolic network. […] Together with a previous review, the facts presented above allow us to propose that accumulation of harmful lipids or generation of signaling intermediates can interfere with immune regulation in cardiac tissues and vice versa; they can form a vicious cycle of immune-metabolic dysregulation and in turn hurt cardiac functions.

• #40 Pathological basis of cardiac arrhythmias: vicious cycle of immune-metabolic dysregulation

  https://www.oatext.com/pathological-basis-of-cardiac-arrhythmias-vicious-cycle-of-immune-metabolic-dysregulation.php

  Immunometabolic disorders involve dysregulation of multiple organelles during cardiac injuries and the ensuing arrhythmia. ER stress and mitochondrial oxidative stress intersect immune injury and metabolic disorder, thereby highly representing malfunctions of immunometabolic network in arrhythmogenesis. […] We propose that ER is an important immunometabolic hub in the cardiac pathogenesis and the ensuing arrhythmias. […] Significant increase in ROS production is a primary cause of cardiomyocyte apoptosis in diabetic cardiomyopathy as well as I/R injury to the heart. […] The interplay between Ca2+ oscillation and MPTP promotes the reperfusion-induced cardiomyocyte injury. […] Immune injuries and metabolic disorders are the central risk factors for CAD, but our current knowledge of the mechanisms underlying arrhythmias is still insufficient. Full understandings of the mechanisms underlying immunometabolic disorder-associated arrhythmias, particularly vicious cycle of immune-metabolic dysregulation, will help for designing more targeted therapies to block the pathogenesis of arrhythmias by suppressing ER stress and mitochondrial oxidative stress, thereby greatly reducing the incidence of arrhythmias and the mortality from CVDs.

• #41 New Mechanism For Cardiac Arrhythmia Discovered | ScienceDaily

  https://www.sciencedaily.com/releases/2008/09/080918101529.htm

  Virus infections can cause cardiac arrhythmia. Scientists have now discovered the molecular mechanism. They have demonstrated that the receptor which the virus uses to infect heart cells is normally necessary for regular heart beat. Likewise, when the receptor is absent, arrhythmia occurs. […] The researchers assume that both the virus infection and the autoimmune disease can block the receptor which, in turn, disrupts the heart’s normal rhythm. […] When CAR is missing, the signal can not be passed on and the heart does not beat properly. […] Professor Gotthardt now wants to investigate whether CAR is blocked in patients with arrhythmia. „However, it does not always have to be connected to a virus infection,” he says. „The body’s own antibodies directed against CAR could cause the disease as well.”

• #42

  https://journals.lww.com/jtrauma/fulltext/9900/pad2_disturbs_cardiomyocyte_calcium_homeostasis_by.974.aspx

  PAD2 protein levels were significantly elevated in the peripheral blood of patients with hemorrhagic shock. […] Pad2 knockout improved calcium homeostasis in the sarcoplasmic reticulum of cardiomyocytes and alleviated post-shock arrhythmia in mice. […] During myocardial hypoxia occurs in hemorrhagic shock, PAD2 reduces SERCA2a enzyme activity by citrullination, disrupting myocardial calcium homeostasis. […] Peptidylarginine deiminase 2 gene deficiency or inhibition improves ventricular arrhythmias and increases survival following hemorrhagic shock. […] In this study, we first show that PAD2 induced lethal arrhythmia after hemorrhagic shock by disturb cardiomyocyte calcium homeostasis. And PAD2 inactivate SERCA2a by citrullination. […] PAD2 plays a crucial role in protein citrullination, a posttranslational modification that alters protein function.

• #43

  https://journals.lww.com/jtrauma/fulltext/9900/pad2_disturbs_cardiomyocyte_calcium_homeostasis_by.974.aspx

  The peptidylarginine deiminase (PAD) plays a crucial role in protein citrullination, a posttranslational modification that alters protein function. […] This study investigates the role of PAD2 in regulating cardiomyocyte function by analyzing the effects of PAD2 knockout or inhibition on cardiac arrhythmias in hemorrhagic shock mouse models. […] Our study revealed PAD2 upregulation in human arrhythmia cases, indicating its potential role in arrhythmias after hemorrhagic shock. […] These findings reveal that PAD2 mediates arrhythmias through disturbing SR calcium homeostasis by interfering with SR calcium content and recovery rates. […] We here provide novel evidence that PAD2 induces the citrullination of SERCA2a, a modification that inhibits its enzymatic activity. […] This inhibition prevents PAD2 from deiminating arginine residues, thereby reducing its biological effects. […] In conclusion, we find that PAD2 plays a critical role in the pathogenesis of hemorrhagic shock-induced arrhythmias by regulating SERCA2a activity through citrullination.

• #44 Society for Cardiovascular Angiography and Interventions

  https://www.healio.com/news/cardiology/20250506/cannabis-use-disorder-among-those-with-heart-failure-may-increase-mi-shock-arrhythmias

  Among patients with heart failure, those with cannabis use disorder had elevated odds for cardiogenic shock, MI and arrhythmias, researchers reported at the Society for Cardiovascular Angiography and Interventions Scientific Sessions. […] After adjustment for demographics, compared with nonusers, patients with cannabis use disorder had lower odds of mortality (adjusted OR = 0.51; 95% CI, 0.35-0.77; P.01) and respiratory failure (aOR = 0.75; 95% CI, 0.69-0.83; P.001) but higher odds of cardiogenic shock (aOR = 1.27; 95% CI, 1.08-1.49; P.01), MI (aOR = 1.5; 95% CI, 1.27-1.77; P.01) and arrhythmias (aOR = 1.48; 95% CI, 1.21-1.97; P.01), Ishaq and colleagues found. […] The negative cardiac effects are associated with the frequency of use, Ishaq told Healio. The more you are using it, the worse prognosis you are going to have in terms of MI, arrhythmias, cardiogenic shock, etc. If you use it less, you will have less of these bad outcomes. If you are using it chronically, that can lead to endothelial dysfunction, which can produce atherosclerosis.

• #45 Discovering a new cardiac arrhythmia mechanism | Mightex | Stimulation and Imaging for Life Science Research

  https://www.mightexbio.com/discovering-a-new-cardiac-arrhythmia-mechanism/

  Discovering a new cardiac arrhythmia mechanism in neonatal rat atrial monolayers using patterned illumination. Understanding how cardiac arrhythmias initiate and maintain themselves is essential for developing novel medical intervention methods. […] One such contradiction is the observation of patients electrogram signals that show abnormal behaviour in a small region, while the rest of the heart shows normal/sinus rhythm. We formulated a hypothesis for a possible mechanism that could underlie these unconventional dynamics. Our proposed mechanism consists of a small electrically isolated region inside a main body of excitable cardiac cells. This small area would be connected to the rest of the cells by a small connective bridge/isthmus. Electrical excitation waves would then be able to rotate inside this small electrically isolated region (which is called reentry) without affecting the rest of the cells (and giving rise to local abnormal electrograms), thereby effectively being trapped. For this reason, we call this phenomenon trapped reentry. However, under changed isthmus properties, the trapped signal might abruptly escape, resulting in an arrhythmia. […] We concluded that our hypothesis of trapped reentry was correct, and that it might be the underlying cause of the peculiar observation of abnormal electrograms under normal cardiac rhythm.

• #46 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-cardiac-arrhythmias-articulo-S1885585711006086

  Cardiac arrhythmias are prevalent among humans across all age ranges and may occur in the setting of underlying heart disease as well as in structurally normal hearts. […] The 3 main mechanisms responsible for cardiac arrhythmias are automaticity, triggered activity, and reentry. […] Understanding the mechanisms of arrhythmias is helpful to the appropriate management and treatment of all arrhythmia types. […] The mechanisms responsible for cardiac arrhythmias may be divided into disorders of impulse formation, disorders of impulse conduction or a combination of both. […] The hallmark of normal automaticity is overdrive suppression. […] Abnormal automaticity is thought to play a role in cases of elevated extracellular potassium, low intracellular pH, and catecholamine excess. […] Triggered activity (TA) is defined by impulse initiation caused by afterdepolarizations (membrane potential oscillations that occur during or immediately following a preceding AP).

• #47 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-cardiac-arrhythmias-articulo-S1885585711006086

  Delayed Afterdepolarization-Induced Triggered Activity […] Early Afterdepolarization-Induced Triggered Activity […] Reentry has been divided in 2 main groups: anatomical or classic reentry, where the circuit is determined by anatomical structures, and functional reentry, which in turn includes different mechanisms. […] Prerequisites for reentry include: A substrate: the presence of joined myocardial tissue with different electrophysiological properties, conduction, and refractoriness. […] The classic reentry mechanism is based on an inexcitable anatomical obstacle surrounded by a circular pathway in which the wavefront can reenter, creating fixed and stable reentrant circuits. […] Initiation and maintenance of reentry will depend on the conduction velocity and refractory period of each pathway, which determines the wavelength.

• #48 Mechanisms of Cardiac Arrhythmias – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-mechanisms-cardiac-arrhythmias-articulo-S1885585711006086

  Clinical examples: AV reentrant tachycardia associated with a bypass tract, AV nodal reentrant tachycardia, atrial flutter, bundle branch reentry VT, post-infarction VT. […] In functional reentry, the circuit is not determined by anatomic obstacles; it is defined by dynamic heterogeneities in the electrophysiologic properties of the involving tissue. […] The predominant mechanisms underlying most VTs are abnormal automaticity, TA, and reentry. […] The initiation and maintenance of these tachyarrhythmias remain unknown; however, previous work supports a similar mechanism as suspected in AF.

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