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Volume 4, Issue 3, Supplement,
, Pages S17-S23
In 1999, Haissaguerre et al published a landmark article showing that atrial fibrillation can be initiated by electrical activity in the pulmonary veins. Not only does it appear that electrical activity in the veins initiates fibrillation, but it also may be responsible for perpetuating fibrillation. Subsequently, similar evidence has suggested that other thoracic veins (vena cavae, coronary sinus, ligament of Marshall) initiate and perpetuate atrial fibrillation. How does electrical impulse initiation occur in the veins? The results of numerous in vivo and in vitro studies on this subject have not conclusively defined a mechanism. Impulse initiation by automaticity and triggered activity as well as impulse initiation resulting from reentry have been suggested. In this article, we focus only on those data suggesting the possibility that triggered activity initiates and/or perpetuates atrial fibrillation.
In 1999, Haissaguerre et al published a landmark article showing that atrial fibrillation can be initiated by electrical activity in the pulmonary veins.1 Not only does it appear that electrical activity in the veins initiates fibrillation, but it also may be responsible for perpetuating fibrillation. Subsequently, similar evidence has suggested that other thoracic veins (vena cavae, coronary sinus, ligament of Marshall) initiate and perpetuate atrial fibrillation.1
How does electrical impulse initiation occur in the veins? The results of numerous in vivo and in vitro studies on this subject have not conclusively defined a mechanism. Impulse initiation by automaticity and triggered activity as well as impulse initiation resulting from reentry have been suggested. The results of ablation procedures in preventing atrial fibrillation are consistent with both mechanisms. In this article, we focus only on those data suggesting the possibility that triggered activity initiates and/or perpetuates atrial fibrillation. Our opinion from a review of the literature is that both triggered activity and reentry are involved in the genesis of atrial fibrillation but that the relative importance of each cannot be determined at present.
Triggered activity is a term used to describe impulse initiation in cardiac fibers that is dependent on afterdepolarizations.2 Afterdepolarizations are oscillations in membrane potential that follow the upstroke of an action potential. Two kinds of afterdepolarizations may cause triggered activity. One occurs early, during phase 2 or 3 repolarization of the action potential [early afterdepolarizations (EADs)]. The other is delayed until repolarization is complete or nearly complete [delayed afterdepolarizations (DADs)]. When either kind of afterdepolarization is large enough to reach the threshold potential for activation of a regenerative inward current, action potentials result and are referred to as “triggered.” Therefore, a key characteristic of triggered activity is that, to occur, at least one action potential must precede it (the trigger).
Afterdepolarizations and triggered activity have been demonstrated in isolated cardiac tissues and cells using transmembrane or patch clamp recordings of electrical activity. However, the demonstration that triggered activity is a cause of arrhythmias in vivo, such as atrial fibrillation, is a major problem that is not completely solved. It has not been possible to reliably record transmembrane potentials demonstrating afterdepolarizations in vivo. Although some studies show what has been interpreted to be afterdepolarizations in monophasic action potentials, the validity of such recordings has been questioned because motion artifact can produce deflections that resemble afterdepolarizations. One method often used to demonstrate that triggered activity may be a cause of an arrhythmia is removing tissue from a region of the arrhythmic heart and showing that afterdepolarizations can be recorded from the cells of that tissue. However, the problem always exists that isolation and superfusion of cardiac tissues and cells may alter their properties. Thus, what is recorded in an isolated preparation may not always resemble what occurs in situ.
Because of these problems, it has been proposed that the mechanism of an arrhythmia in the in situ heart can be deduced from the response of the arrhythmia to cardiac pacing.3 The following is a brief summary of the stimulation protocols and the response of arrhythmias to stimulation that may identify triggered activity.
The amplitude of DADs increases with a decrease in the cycle length at which action potentials occur until the afterdepolarization reaches threshold to cause triggered activity. Therefore, triggered arrhythmias caused by DADs in the in situ heart should be initiated by either overdrive pacing or programmed premature stimulation. Because automaticity is not initiated by pacing, automatic arrhythmias should be readily distinguished from triggered impulses arrhythmias (see Chapter 1 in Wit and Janse3). Reentrant arrhythmias also can be induced by the same stimulation. However, triggered activity caused by DADs is more easily induced by rapid pacing than by a single premature stimulus, whereas reentry is more easily induced by premature stimulation.
During initiation of DAD-dependent triggered rhythms, as the pacing cycle length (or coupling interval of premature impulses) decreases, the coupling interval from the last stimulated impulse to the first impulse of tachycardia should decrease (a direct relationship) because at short cycle lengths, the coupling interval of the afterdepolarizations to the proceeding action potential decreases. Such a direct relation is not expected during initiation of reentrant arrhythmias, in which slowing of conduction causes an inverse relationship.
Both triggered rhythms and reentrant rhythms can be terminated by overdrive stimulation or single premature impulses.3 Automatic rhythms caused by normal automaticity show the phenomenon of overdrive suppression but are not terminated, whereas those caused by abnormal automaticity are little affected. Another feature of the response to electrical stimulation that differentiates DAD-induced triggered activity from reentry is that reentrant rhythms, but not triggered rhythms, can be entrained.3
Arrhythmias caused by EADs, which result from prolonged action potential duration, have been shown not to be inducible by overdrive or premature stimulation, but they can be initiated by slowing the basic heart rate. However, more recent studies have suggested that, under certain circumstances, EAD-dependent triggered activity can be induced by rapid pacing in pulmonary vein preparations (see later). Electrical stimulation (premature or overdrive) in general is not expected to terminate triggered rhythms caused by EADs. The response should be similar to that of abnormal automaticity, which shows resetting but little overdrive suppression.
The response of initiators and perpetuators to electrical stimulation in vivo is mostly lacking, so proof that triggered activity is related to onset and perpetuation of atrial fibrillation is mostly circumstantial. Most of the evidence for involvement of triggered activity in atrial fibrillation comes from studies on isolated tissues and cells.
Although the pulmonary veins are the most important site for initiation of atrial fibrillation, we start with a description of triggered activity in the coronary sinus because, in our opinion, the musculature of the coronary sinus shows the most clear-cut evidence of triggered activity. Atrial myocardium extends into the coronary sinus from its orifice. Some myocytes resembling the transitional cells of the sinus node are interspersed among working atrial myocytes and connected to them by scattered gap junctions. The structure of these cells in the coronary sinus resemble the structure of cells proposed to be the automatic cells in the sinus node (Albala and Fenoglio, unpublished observations).
Rapid atrial tachycardias have been shown by mapping techniques to emanate from the coronary sinus.4 Involvement of the coronary sinus in atrial fibrillation is evidenced by the demonstration that bursts of rapid activity in the coronary sinus, faster than in the atria, occurred in response to the rapid atrial pacing that initiated atrial fibrillation.5 In some patients with atrial fibrillation, rapid repetitive activity in the musculature of the coronary sleeve may contribute to maintenance of the arrhythmia. Isolation of the coronary sinus from atrial myocardium has been shown to prevent atrial fibrillation in patients who had undergone pulmonary vein ablation that did not prevent fibrillation. Other clinical studies have shown that the initiator of atrial fibrillation can sometimes be in the vicinity of the coronary sinus.6, 7, 8
These clinical data, however, do not address the mechanism of impulse initiation in any detail. Rapid coronary sinus activity and atrial fibrillation are initiated by atrial pacing, but this does not eliminate the possibility of pacing-induced reentry. The other characteristics necessary to suggest DAD-induced triggered activity (e.g., a direct relationship between pacing cycle length and the first cycle length of the induced activity) have not been obtained. That the coronary sinus in situ is capable of triggered activity has been shown in an experimental study on the canine heart, using the characteristics of response to electrical stimulation.9, 10 Such studies in the human heart are needed to relate triggered activity to atrial fibrillation initiation and maintenance.
A large body of information describes the cellular electrophysiology of coronary sinus musculature. Mapping of isolated preparations composed of coronary sinus and atrial musculature from the canine heart showed that two different regions are capable of impulse initiation in the presence of norepinephrine, one just outside the orifice of the coronary sinus and the other well within the walls of the coronary sinus.11 The action potentials of musculature inside the coronary sinus resemble atrial action potentials but have a small plateau phase. However, the cells have a less negative resting potential that may result from a sodium leak current. In the absence of electrical stimulation, this inward current causes a progressive loss of membrane potential that may result in a loss of excitability.12 Norepinephrine causes DADs and triggered activity in musculature inside the coronary sinus (Figure 1), while causing spontaneous diastolic (pacemaker) depolarization in cells outside the coronary sinus orifice. Triggered activity in coronary sinus musculature is initiated by either a critically shortened stimulation cycle length (Figure 2) or critically timed premature impulse.11 DADs in coronary sinus are caused by a transient inward current similar to the transient inward current caused by cardiac glycosides in other tissues.13, 14 It likely is related to calcium release from the sarcoplasmic reticulum.15 Enhancing electrogenic sodium pump current during prolonged periods of triggered activity can terminate it.16
Atrial muscle extends into the pulmonary veins. An extensive literature shows that electrical activity in this pulmonary vein musculature is related to the onset and perpetuation of atrial fibrillation.1, 17 Ablation of pulmonary vein musculature can prevent atrial fibrillation. The mechanism for impulse origin in pulmonary veins is uncertain; automaticity, triggered activity, and reentry all have been proposed.18
Specialized cardiac cells that are associated with pacemaking, resembling pale (P) cells and Purkinje cells, have been described in rat19 and human pulmonary vein20 and in some21 but not all22, 23 studies on canine pulmonary veins. The link suggesting triggered activity in pulmonary veins to atrial fibrillation is that rapid pacing of the atria can initiate pulmonary vein activity. However, no other evidence from in situ studies has shown the expected features of triggered activity in response to pacing protocols that we described earlier. A majority of data suggesting a possible role of triggered activity has come from in vitro studies on tissues and cells. The results from studies on different species are somewhat varied and add to the confusion as to whether pulmonary vein musculature is capable of triggered activity.
Automaticity, DADs and triggered activity do not readily occur in in vitro preparations of canine pulmonary vein where action potentials resemble atrial muscle and are characterized by rapid upstrokes (Figure 2C, trace labeled “PV”).23, 24, 25 Pulmonary vein muscle fibers have a less negative membrane potential than does atrial muscle because of a smaller IK1, slower phase 0 upstroke velocity (Vmax) likely caused by the reduced membrane potential, and shorter action potential duration associated with larger IKr and IKs. Resting membrane potential and upstroke velocity are decreased more in the distal vein than in the proximal vein.23, 24, 25 The reduced upstrokes and structural anisotropy23, 26 along with differences in connexin expression22 and heterogeneity of action potential duration may cause reentry, a proposed mechanism for the rapid impulse initiation that can originate in the veins.27 Spontaneous activity arising just proximal to the venous ostium in the presence of isoproterenol, with an increased rate after rapid pacing (suggesting triggered activity), has been described in only one study on veins from normal dog hearts.27 Pacemaker potentials or afterdepolarizations were not evident, so a role for triggered activity is uncertain.
Canine pulmonary vein muscle can initiate rapid activity under special experimental conditions. One condition is the simultaneous activation of parasympathetic and sympathetic nerves in vitro (Figure 2). This rapid activity is caused by EADs during phase 3 repolarization that induces triggered activity.28, 29 Although the traditional mechanism for EAD-induced triggered activity is dependent on action potential prolongation with reactivation of inward Ca2+ or Na+ current during the plateau phase, the proposed mechanism for EADs resulting from autonomic nerve activation in pulmonary veins is not dependent on action potential prolongation. The short duration of the atrial action potential in pulmonary vein muscle is associated with a peak Ca2+ transient (as deduced from force measurements) occurring during late repolarization rather than during the plateau phase. Parasympathetic nerve activation increases this disparity by accelerating repolarization to make action potential duration even shorter. Presumably [Ca2+]i from the calcium transient remains elevated at a time when the membrane potential has mostly repolarized and is negative to the equilibrium potential for the Na/Ca exchanger current. Inward exchanger current is activated under these conditions. It is proposed that sympathetic activation augments the Ca2+ transient, enhances EADs, and promotes triggering. Suppression of Na/Ca exchange suppresses EAD-induced triggered activity.28 Although the autonomic nervous system sometimes is involved in the occurrence of atrial fibrillation in experimental animals29 or in patients,30 how often its participation is obligatory is uncertain. Late phase 3 EAD-triggered activity caused by these mechanisms may occur only under limited circumstances.
From these canine studies, triggered activity does not appear to be a normal intrinsic property of normal pulmonary vein myocardium; however, the properties of the vein musculature might be altered under conditions that favor the occurrence of atrial fibrillation. For example, stretch of the atria in a sheep model of stretch-related AF causes focal activity arising in the veins.31 In a canine model of pacing-induced heart failure, atrial tachycardia and fibrillation occur that may arise in the pulmonary veins.17, 32, 33 There is evidence that atrial tachycardia in this animal model is caused by DAD-induced triggered activity, some of which arises near or in pulmonary veins, although atrial muscle also may be a source of impulse initiation. In superfused pulmonary vein preparations from a rapid-pacing induced heart failure model, both action potentials with spontaneous diastolic depolarization and automatic activity and those with phase 2 EADs have been recorded.34
In contrast to the results of studies in tissues, both DADs and EADs and triggered activity have been found to be prevalent in single pulmonary vein myocytes isolated from normal canine pulmonary vein myocardium34 as well as from myocytes from pulmonary vein obtained from dogs with pacing-induced heart failure (Figure 3).35 Reasons why triggered activity is more prevalent in single myocytes are uncertain. Electrotonic inhibition of pacemaking cells by nonpacemaking cells may occur in tissues and not in isolated myocytes.36 Additionally, isolation of single myocytes may result in abnormal calcium loading that can cause afterdepolarizations. The validity of results from isolated myocyte studies has been questioned, and some results have been attributed to experimental artifacts.24 In our opinion, studies on automaticity and triggered activity in isolated myocytes should be repeated by other laboratories.
As in the dog, rabbit pulmonary vein tissue superfused in vitro shows typical atrial action potentials, is not spontaneously active, and does not have afterdepolarizations or triggered activity.37 Addition of ryanodine to the superfusate caused depolarization of the resting potential, increase in plateau height, development of pacemaker activity, and rapid repetitive action potentials following pacing that likely were caused by DADs (Figure 4).37 This behavior is consistent with the effects of ryanodine at low concentrations in locking the sarcoplasmic reticulum Ca2+ release channel, the ryanodine receptor (RyR), in a subconductance state, causing Ca2+-independent Ca2+ release from the sarcoplasmic reticulum.38 Ca2+ leakage during diastole causes traveling Ca2+ waves, increasing Ca2+ dependent ionic currents that may cause DADs.39, 40 The inward current causing DADs in this experimental model may be an Na/Ca exchanger current.
Other sites of triggered activity that may be related to the onset and perpetuation of atrial fibrillation include vena cavae, ligament of Marshall, atrial muscle, and mitral valves. Ectopic activity has been recorded from the cardiac muscle that extends into the vena cavae41 associated with onset of atrial fibrillation.42 Isoproterenol infusion and burst pacing, both of which can cause triggered activity, initiated atrial fibrillation with onset attributed to vena cava activity because the atrial fibrillation was prevented by ablation at the vein orifice. Isolated cardiomyocytes from the vena cavae have been shown to have pacemaker activity, DADs, and triggered activity.43
An electrically active muscle sleeve occurs in the ligament of Marshall, continuous with the muscle sleeve around the coronary sinus.44 Rapid activity in this muscle sleeve has been shown to precede the onset of atrial fibrillation in some patients with ablation of the ligament preventing fibrillation.45, 46 Action potentials recorded from the ligament in vitro resemble working atrial myocardial action potentials.1 A role of triggered activity in the focal impulse initiation seen in situ has not been established.
DADs and triggered activity in the presence of catecholamines readily occur in the atrial muscle that extends into the mitral valve.47 Although a role for valve impulse initiation in atrial fibrillation has not been described, a relationship is possible. Under certain circumstances, triggered activity can also occur in working atrial muscle,48 particularly in the presence of underlying disease such as a cardiomyopathy.49
Although it is well accepted that electrical activity originating in the pulmonary and other thoracic veins is sometimes intimately related to the onset and perpetuation of atrial fibrillation, the mechanism for impulse initiation is uncertain. Triggered activity does not appear to be a normal property of the atrial muscle that lines the pulmonary veins, although it may be a normal property of coronary sinus muscle. Thus, studies on normal canine hearts, although they define the normal
- G. MeissnerRyanodine activation and inhibition of the Ca release channel of sarcoplasmic reticulum
J Biol Chem
- E. Patterson et al.Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins
J Am Coll Cardiol
- T.M. Wang et al.Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves: a contradictory report
Int J Cardiol
- Y. Okuyama et al.High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure
J Am Coll Cardiol
- G.-N. Tseng et al.Characteristics of a transient inward current that causes delayed afterdepolarizations in atrial cells of the canine coronary sinus
J Mol Cell Cardiol
- P.F. Cranefield et al.
Cardiac Arrhythmias: The Role of Triggered Activity
- A.L. Wit et al.
The Ventricular Arrhythmias of Ischemia and InfarctionElectrophysiological Mechanisms
- M. Volkmer et al.
Focal atrial tachycardia originating from the musculature of the coronary sinus
J Cardiovasc Electrophysiol
- H. Oral et al.
Role of coronary sinus in maintenance of atrial fibrillation(Video) Arrhythmia Overview - Mechanism of bradyarrhythmia and tachyarrhythmia
J Cardiovasc Electrophysiol
Coronary sinus as an arrhythmogenic structure
J Cardiovasc Electrophysiol
Conduction delay within the coronary sinus in Humans: implications for atrial arrhythmias
J Cardiovasc Electrophysiol
Electrical disconnection of the coronary sinus by radiofrequency catheter ablation to isolate a trigger of atrial fibrillation
J Cardiovasc Electrophysiol
Characteristics of initiation and termination of catecholamine-induced triggered activity in atrial fibers of the coronary sinus
The response to overdrive pacing of triggered atrial and ventricular arrhythmias in the canine heart
Triggered and automatic activity in the canine coronary sinus
The basis for the membrane potential of quiescent cells of the canine coronary sinus
Effects of reducing [Na+]o on catecholamine-induced delayed afterdepolarizations in atrial cells
Am J Physiol Heart Circ Physiol
The effects of caffeine and ryanodine on the electrical activity of the canine coronary sinus
Electrogenic sodium extrusion can stop triggered activity in the canine coronary sinus
Basic electrophysiology of the pulmonary veins and their role in atrial fibrillation: precipitators, perpetuators, and perplexers
J Cardiovasc Electrophysiol
Node-like cells in the myocardial layer of the pulmonary vein of rats: an ultrastructural study
Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation
J Cardiovasc Electrophysiol
Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium
- Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis
2018, Translational Research
Our previous study proved that exogenous H2O2 significantly increased PV spontaneous activity by increasing the opening probability of ryanodine receptors and calcium release.17 Throughout the surgical period, there are several variables specific to cardiac surgery which can both trigger events in PVs and substrate remodeling in atria, thus meeting necessary conditions for AF formulation.18-20 Accordingly, a pericardiotomy is deemed a complex of autonomic alteration, cardiac inflammation, and rising oxidative stress, all of which increase arrhythmogenesis through neurological or upstream modulation and exert significant impacts on the pathophysiology of AF.21,22(Video) Intro to EKG Interpretation - Mechanisms of Tachyarrhythmias
Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4%), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7%) than in control PVs (11.1%), MPT0E014-treated PVs (16.7%), and MPT0E014-treated opPVs (12.5%). The AP duration at a repolarization extent of 90% (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 μM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90%) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3%) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.
- The molecular and functional identities of atrial cardiomyocytes in health and disease
2016, Biochimica et Biophysica Acta - Molecular Cell Research
In patients, atrial tissue remodelling increases the risk for AF and is identified by significant transmural hypertrophy, atrial dilation, and fibrosis . The mechanisms of AF are very complex, involving both cell- and tissue-specific forms of electrical dysfunction referred to as ectopy and reentry, respectively (for in-depth reviews see [19,106,107]). Here, we summarize major cell-specific electrophysiological and metabolic AF mechanisms with a focus on common forms of cellular atrial pathobiology.
Atrial cardiomyocytes are essential for fluid homeostasis, ventricular filling, and survival, yet their cell biology and physiology are incompletely understood. It has become clear that the cell fate of atrial cardiomyocytes depends significantly on transcription programs that might control thousands of differentially expressed genes. Atrial muscle membranes propagate action potentials and activate myofilament force generation, producing overall faster contractions than ventricular muscles. While atria-specific excitation and contractility depend critically on intracellular Ca2+ signalling, voltage-dependent L-type Ca2+ channels and ryanodine receptor Ca2+ release channels are each expressed at high levels similar to ventricles. However, intracellular Ca2+ transients in atrial cardiomyocytes are markedly heterogeneous and fundamentally different from ventricular cardiomyocytes. In addition, differential atria-specific K+ channel expression and trafficking confer unique electrophysiological and metabolic properties. Because diseased atria have the propensity to perpetuate fast arrhythmias, we discuss our understanding about the cell-specific mechanisms that lead to metabolic and/or mitochondrial dysfunction in atrial fibrillation. Interestingly, recent work identified potential atria-specific mechanisms that lead to early contractile dysfunction and metabolic remodelling, suggesting highly interdependent metabolic, electrical, and contractile pathomechanisms. Hence, the objective of this review is to provide an integrated model of atrial cardiomyocytes, from tissue-specific cell properties, intracellular metabolism, and excitation–contraction (EC) coupling to early pathological changes, in particular metabolic dysfunction and tissue remodelling due to atrial fibrillation and aging. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
- Embryonic development of the right ventricular outflow tract and arrhythmias
2016, Heart Rhythm
- Morphology and pathophysiology of target anatomical sites for ablation procedures in patients with atrial fibrillation. Part I: Atrial structures (atrial myocardium and coronary sinus)
2013, International Journal of Cardiology
Experimental and clinical evidence suggests that the natural history of atrial fibrillation is characterised by increased structural remodelling, which may play a pivotal role in maintaining the arrhythmia and clinically favours progression from paroxysmal to persistent atrial fibrillation. In this setting, anti-arrhythmic therapy gradually becomes inefficient, and this limitation has led to the introduction of new non-pharmacological interventions such as surgical or catheter ablation. At the same time, interest in the functional morphology and electrophysiological properties of the atria and their related anatomical structures has greatly increased. This article is the first of a two-part review whose main purpose is to describe the anatomical and functional details of some of the principal anatomical locations that are commonly targeted by ablative procedures to treat this supraventricular arrhythmia. In particular, this manuscript has dealt with the atrial structures (atrial myocardium and coronary sinus). General information on ablation procedures has also been provided.
Targeting late I<inf>CaL</inf> to close the window to ventricular arrhythmias
2021, Journal of General Physiology
Children with heart transplants: Lessons learned from 774 visits at a primary community clinic
2020, Pediatric Transplantation
Research articleSex Differences in Cardiac Electrophysiology and Clinical Arrhythmias: Epidemiology, Therapeutics, and Mechanisms
Canadian Journal of Cardiology, Volume 30, Issue 7, 2014, pp. 783-792
Sex differences in cardiac electrophysiological properties and arrhythmias are evident in epidemiologic and investigative studies as well as in daily patient care. At the supraventricular level, women are at increased risk of sick sinus syndrome and atrioventricular (AV) node re-entrant tachycardia, whereas men manifest more AV block and accessory pathway–mediated arrhythmias. At the ventricular level, women are generally at higher risk of long QT–associated arrhythmias, whereas men are more likely to present with early repolarization, idiopathic ventricular fibrillation, and Brugada syndromes. Great advances have been made in unraveling the fundamental mechanisms underlying sex differences in ventricular arrhythmias, particularly those associated with abnormal repolarization. Conversely, the basis for male-predominant arrhythmia risk in structural heart disease and differences in supraventricular arrhythmia susceptibility are poorly understood. Beyond biological differences, arrhythmia occurrence and patient care decisions are also influenced by gender-related factors. This article reviews the current knowledge regarding the nature and underlying mechanisms of sex differences in basic cardiac electrophysiology and clinical arrhythmias.
Les différences sur les propriétés électrophysiologiques cardiaques et les arythmies observées entre les sexes sont aussi évidentes en épidémiologie et lors d’études approfondies que dans les soins quotidiens des patients. Au niveau supraventriculaire, les femmes sont exposées à une augmentation du risque de maladie du sinus et de tachycardie par réentrée nodale auriculoventriculaire (AV), tandis que les hommes manifestent plus de bloc AV et d’arythmies par l’intermédiaire d’une voie accessoire. Au niveau ventriculaire, les femmes sont généralement exposées à un risque plus élevé d’arythmies associées au QT long, tandis que les hommes sont plus susceptibles de présenter une repolarisation précoce, une fibrillation ventriculaire idiopathique et un syndrome de Brugada. Des avancées importantes ont été réalisées dans la recherche des mécanismes fondamentaux sous-jacents aux différences observées entre les sexesau cours d’arythmies ventriculaires, particulièrement celles associées àune repolarisation anormale. De façon inverse, les fondements de la prédominance masculine du risque d’arythmie lors de cardiopathie structurelle et les différences liées à la vulnérabilité de l’arythmie supraventriculaire sont mal compris. Au-delà des différences biologiques, la survenue de l’arythmie et les décisions relatives aux soins des patients sont également influencées par les facteurs liés au sexe. Cet article passe en revue les connaissances actuelles concernant la nature et les mécanismes sous-jacents aux différences observées entre les sexes dans l’électrophysiologie cardiaque de base et les arythmies cliniques.
Research articleNew-Onset Atrial Fibrillation After Acute Myocardial Infarction and Its Relation to Admission Biomarkers (from the TRIUMPH Registry)
The American Journal of Cardiology, Volume 112, Issue 9, 2013, pp. 1390-1395(Video) Mechanisms of cardiac arrhythmias | Tachyarrhythmias | Cardiovascular Pathophysiology
Atrial fibrillation (AF) is an independent predictor of mortality after acute myocardial infarction (AMI). We analyzed the relation between biomarkers linked to myocardial stretch (NT-pro-brain natriuretic peptide [NT-proBNP]), myocardial damage (Troponin-T [TnT]), and inflammation (high-sensitivity C-reactive protein [hs-CRP]) and new-onset AF during AMI to identify patients at high risk for AF. In a prospective multicenter registry of AMI patients (from the Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction: Patients' Health status registry), we measured NT-proBNP, TnT, and hs-CRP in patients without a history of AF (n= 2,370). New-onset AF was defined as AF that occurred during the index hospitalization. Hierarchical multivariate logistic regression models were used to determine the association of biomarkers with new-onset AF, after adjusting for other covariates. New-onset AF was documented in 114 patients with AMI (4.8%; mean age 58years; 32% women). For each twofold increase in NT-proBNP, there was an 18% increase in the rate of AF (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03 to 1.35; p <0.02). Similarly, for every twofold increase in hs-CRP, there was a 15% increase in the rate of AF (OR 1.15, 95% CI 1.02 to 1.30; p=0.02). TnT was not independently associated with new-onset AF (OR 0.96, 95% CI 0.85 to 1.07; p= 0.3). NT-proBNP and hs-CRP were independently associated with new in-hospital AF after MI, in both men and women, irrespective of race. Our study suggests that markers of myocardial stretch and inflammation, but not the amount of myocardial necrosis, are important determinants of AF in the setting of AMI.
Research articleUnmasking atrial repolarization to assess alternans, spatiotemporal heterogeneity, and susceptibility to atrial fibrillation
Heart Rhythm, Volume 13, Issue 4, 2016, pp. 953-961
Detection of atrial repolarization waves free of far-field signal contamination by ventricular activation would allow investigation of atrial electrophysiology and factors that influence susceptibility to atrial tachycardia and atrial fibrillation (AF).
The purpose of this study was to identify means for high-resolution intracardiac recording of atrial repolarization (Ta) waves using standard clinical electrocatheters and to assess fundamental electrophysiologic properties relevant to AF risk.
In alpha-chloralose anesthetized Yorkshire pigs, we studied effects of vagus nerve stimulation (VNS) on PTa and QT intervals and effects of acute atrial ischemia or administration of intrapericardial acetylcholine followed by intravenous epinephrine on susceptibility to AF.
Electrocatheters with closely spaced (1-mm) electrode pairs yielded high-resolution tracings of atrial repolarization waves. These recordings permitted detection of differential effects of right or left VNS, which shortened atrial PTa interval by 30% vs 21% (P <.01) and lengthened QT interval by 1.5% vs 9%, respectively (P <.05). During atrial ischemia, STa segments were elevated 3.4-fold (P <.01), and the threshold for inducing AF was reduced 3.1-fold (P = .004). Ischemia amplified atrial T-wave alternans (TWAa) and spatiotemporal heterogeneity (TWHa) by 23- and 13-fold, respectively, in inverse correlation to AF threshold (r = 0.74, P <.01; r = 0.61, P = .03). TWAa and TWHa increased by 4.5- and 2-fold shortly before autonomically triggered atrial premature beats and AF.
This study used standard electrocatheters to demonstrate that TWAa and TWHa analysis provides means to assess vulnerability to AF without provocative electrical stimuli. These parameters could be evaluated in the clinical electrophysiology laboratory to determine risk for this prevalent arrhythmia and efficacy of contemporary and new agents.
Research articleRotor mapping and ablation: Spinning out of control?
Heart Rhythm, Volume 14, Issue 2, 2017, pp. 198-199
Research articleDynamics of sodium current mediated early afterdepolarizations
Heliyon, Volume 3, Issue 9, 2017, Article e00388
Early afterdepolarizations (EADs) have been attributed to two primary mechanisms: 1) recovery from inactivation of the L-type calcium (Ca) channel and/or 2) spontaneous Ca release, which depolarizes the membrane potential through the electrogenic sodium-calcium exchanger (NCX). The sodium (Na) current (INa), especially the late component of the Na current, has been recognized as an important player to set up the conditions for EADs by reducing repolarization reserve and increasing intracellular Na concentration, which leads to Ca overload. However, INa itself has not been considered as a direct initiator of EADs. A recent experimental study by Horvath et al. has shown that the amplitude of the late component of the Na current is as large as potassium (K) and Ca currents (∼1 pA/pF). This result suggests that INa by itself can exceeds the sum of outward currents and depolarize the membrane potential. In this study, we show that INa can also directly initiate EADs. Mathematical analysis reveals a fundamental dynamical origin of EADs arising directly from the Na channel reactivation. This system has three fixed points. The dynamics of the INa mediated EAD oscillation is different from that of the membrane voltage oscillation of the pacemaker cell, which has only one fixed point.
Research articleRole of inflammatory signaling in atrial fibrillation
International Journal of Cardiology, Volume 287, 2019, pp. 195-200
Atrial fibrillation (AF), the most prevalent arrhythmia, is often associated with enhanced inflammatory response. Emerging evidence points to a causal role of inflammatory signaling pathways in the evolution of atrial electrical, calcium handling and structural remodeling, which create the substrate of AF development. In this review, we discuss the clinical evidence supporting the association between inflammatory indices and AF development, the molecular and cellular mechanisms of AF, which appear to involve multiple canonical inflammatory pathways, and the potential of anti-inflammatory therapeutic approaches in AF prevention/treatment.
Copyright © 2007 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
- drinking excessive amounts of alcohol, particularly binge drinking.
- being overweight (read about how to lose weight)
- drinking lots of caffeine, such as tea, coffee or energy drinks.
- taking illegal drugs, particularly amphetamines or cocaine.
Triggered activity is a term used to describe impulse initiation in cardiac fibers that is dependent on afterdepolarizations 2. Afterdepolarizations are oscillations in membrane potential that follow the upstroke of an action potential.Can emotional upset trigger AFib? ›
Stress can contribute to heart rhythm disorders (arrhythmias) such as atrial fibrillation. Some studies suggest that stress and mental health issues may cause your atrial fibrillation symptoms to worsen.What causes triggered activity of the heart? ›
This is often caused by so called afterdepolarizations (early or delayed afterdepolarizations EADs / DADs) caused by electrical instability in the myocardial cell membrane. A typical example of this is Torsade de Pointes.
- Engage in deep, mindful breathing. ...
- Get some exercise. ...
- Valsalva maneuver. ...
- Practice yoga. ...
- Put some cold water on your face. ...
- Contact a health professional.
In addition to causing high blood pressure, high sodium levels have been linked with a long-term risk of developing AFib. Avoid or reduce salty foods such as pizza, cold cuts, salad dressings, and soups to reduce your risk.
- Avoiding caffeine.
- Getting enough sleep.
- Avoiding or cutting back on alcohol.
- Stopping smoking.
- Staying away from stimulant drugs, including cold medicines that contain pseudoephedrine.
- Finding ways to relax and manage stress.
A heart that beats irregularly, too fast or too slow is experiencing an arrhythmia. A palpitation is a short-lived feeling like a feeling of a heart racing or of a short-lived arrhythmia. Palpitations may be caused by emotional stress, physical activity or consuming caffeine or nicotine.How do I stop heart palpitations when drinking alcohol? ›
“But if you notice heart rhythm abnormalities during or after alcohol consumption, you should strongly consider cutting back or avoiding.” And if you drink, keep it light or moderate (two drinks per day for men, and one per day for women).Can anxiety bring on atrial fibrillation? ›
Studies show that stress and anxiety can worsen symptoms of AFib, but more research is needed to find out if people with anxiety and depression are at greater risk for developing it.
Right now, there's no cure for it. But certain treatments can make symptoms go away for a long time for some people. No matter what, there are many ways to manage AFib that can help you live a healthy, active life.Is atrial fibrillation linked to anxiety? ›
Levels of anxiety and depression seen in people who have a common heart rhythm disorder called atrial fibrillation may be affected by how the heart condition is treated, a new study suggests. Past studies have shown that anxiety, distress and depression are common among people with AFib.Can anxiety cause arrhythmias? ›
Can anxiety contribute to arrhythmias? Yes. As described above, when we are stressed or anxious our heart perceives this as an impending threat, triggering our fight or flight response in which adrenaline is released, which can trigger arrhythmia, in turn triggering an additional release of adrenaline.What is the most common cause of irregular heartbeat? ›
The most common type of arrhythmia is atrial fibrillation, which causes an irregular and fast heart beat. Many factors can affect your heart's rhythm, such as having had a heart attack, smoking, congenital heart defects, and stress. Some substances or medicines may also cause arrhythmias.Can you have AFib with normal heart rate? ›
In some cases it's possible to have A-Fib and still have what appears to be a regular heart rate. Your atria can be fibrillating, even though your heart doesn't beat rapidly.Can a person go in and out of AFib? ›
Episodes of atrial fibrillation may come and go, or they may be persistent. Although A-fib itself usually isn't life-threatening, it's a serious medical condition that requires proper treatment to prevent stroke.Can atrial fibrillation be cured permanently? ›
There May Be No Permanent Cure for Atrial Fibrillation. Researchers say even after irregular heartbeats are treated, they can return and the increased risk for stroke remains. While experiencing atrial fibrillation can be frightening, this type of irregular heartbeat usually won't have harmful consequences by itself.Can atrial fibrillation go away? ›
It is possible to have an atrial fibrillation episode that resolves on its own. Or, the condition may be persistent and require treatment. Sometimes AFib is permanent, and medicines or other treatments can't restore a normal heart rhythm.Can AFib be misdiagnosed? ›
AFib can often be mistaken for other disorders, which makes properly diagnosing AFib complicated. Learn more about how AFib is usually diagnosed and why it may be mistaken for other health or heart conditions.How long is too long for heart palpitations? ›
Ventricular tachycardia is a very rapid, but regular heartbeat of 100 beats or more a minute occurring in the lower chambers (ventricles) of the heart. Sustained heart palpitations lasting more than 30 seconds are considered a medical emergency.
paroxysmal atrial fibrillation – episodes come and go, and usually stop within 48 hours without any treatment. persistent atrial fibrillation – each episode lasts for longer than 7 days (or less when it's treated) permanent atrial fibrillation – when it's present all the time.Can you drink alcohol with atrial fibrillation? ›
Learn about alcohol as a trigger for atrial fibrillation symptoms. Health experts agree that heavy drinking and atrial fibrillation (Afib) don't mix. That's because alcohol can trigger symptoms of the condition, such as heart palpitations.Can you drink wine with AFib? ›
You should avoid drinking alcohol if you have an abnormal heart rhythm. One study, performed in Australia, found that AFib patients who did not drink during a 6-month period had fewer AFib episodes. If you're taking blood thinners, alcohol can raise your risk of bleeding.Which alcohol is good for heart patients? ›
Red wine, in moderation, has long been thought of as heart healthy. The alcohol and certain substances in red wine called antioxidants may help prevent coronary artery disease, the condition that leads to heart attacks.Can stress trigger an AFib episode? ›
How Stress May Trigger an AFib Episode. During times of stress, your body releases stress hormones that can increase your blood pressure and trigger an AFib episode.Is Apple Watch accurate for AFib? ›
The irregular rhythm notification feature on Apple Watch is not constantly looking for AFib. This means it cannot detect all instances of AFib, and people with AFib may not get a notification. If you're not feeling well, you should talk to your doctor even if you don't get a notification.Does the Apple Watch detect AFib? ›
And now… the Apple watch.
The Apple Watch and other wearables are now able to monitor your heart rhythm. The Apple watch can detect irregular heart rhythms, and if it does so 5 times, it will prompt you to record your rhythm. And in that way, it can also be used to diagnose atrial fibrillation.
A left lateral recumbent position increases the dimensions of the left atrium and the right pulmonary veins and thereby increases local myocardial stress (Wieslander et al., 2019).Is AFib considered heart disease? ›
Atrial fibrillation (AF) is a common heart rhythm condition that can cause stroke and heart failure. Read about AF symptoms, causes, risk factors and common triggers. You can also learn about treatment and find ways to manage your condition.Can your mind cause heart palpitations? ›
Many people experience heart palpitations along with anxiety. Anxiety sets off the body's “fight or flight” response as part of the autonomic nervous system (ANS). When you feel uneasy about a situation, your ANS kicks in, increasing your heart rate.
Cardiophobia is defined as an anxiety disorder of persons characterized by repeated complaints of chest pain, heart palpitations, and other somatic sensations accompanied by fears of having a heart attack and of dying.What are the 4 lethal heart rhythms? ›
You will need to be able to recognize the four lethal rhythms. Asystole, Ventricle Tachycardia (VT), Ventricle Fibrillation (VF), and Polymorphic Ventricle Tachycardia (Torsade de pointes).What vitamins help irregular heartbeat? ›
Vitamin C. Arrhythmias and other heart conditions are associated with oxidant stress and inflammation. Antioxidants like vitamin C and vitamin E appear to be effective in reducing these. You can use vitamin C to treat colds, the flu, and even cancer, and it can also help with arrhythmia.What does it feel like when your heart is out of rhythm? ›
Symptoms of arrhythmias include palpitations, feeling dizzy, fainting and being short of breath, although having these symptoms does not always mean you have a heart rhythm problem.Can pulse oximeter detect AFib? ›
Hospital-grade pulse oximeters usually can read through perfusing cardiac arrhythmias such as atrial fibrillation and premature atrial or ventricular contractions.Will AFib always show up on an EKG? ›
It gives your doctor a picture of your heart's overall electrical activity. But because the test is a quick snapshot, a standard EKG won't always catch AFib. Sometimes you'll need a portable heart rhythm monitor to keep tabs on your ticker over a longer time.What are non cardiac causes of atrial fibrillation? ›
Atrial fibrillation (AF) may be caused by many cardiac and non-cardiac conditions, including hypertension, valvular disease (in particular, of the mitral valve), (ischaemic) car- diomyopathy, diabetes mellitus, and thyroid disease.How long does an atrial fibrillation episode last? ›
paroxysmal atrial fibrillation – episodes come and go, and usually stop within 48 hours without any treatment. persistent atrial fibrillation – each episode lasts for longer than 7 days (or less when it's treated) permanent atrial fibrillation – when it's present all the time.Can stress trigger an AFib episode? ›
How Stress May Trigger an AFib Episode. During times of stress, your body releases stress hormones that can increase your blood pressure and trigger an AFib episode.What is the life expectancy of someone with atrial fibrillation? ›
Ten years after diagnosis, the first generation with atrial fibrillation, covering 1972 to 1985, had lived an average of 2.9 fewer years compared to participants without AFib. That gap narrowed to 2.1 years between 1986 and 2000, and to 2.0 years between 2001 and 2015.