What is AF in cardiology?
Atrial fibrillation (AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological alterations promoting AF have been studied extensively in animal models. Atrial tachycardia or AF itself shortens atrial refractoriness and causes loss of atrial contractility. Aging, neurohumoral activation, and chronic atrial stretch due to structural heart disease activate a variety of signaling pathways leading to histological changes in the atria including myocyte hypertrophy, fibroblast proliferation, and complex alterations of the extracellular matrix including tissue fibrosis. These changes in electrical, contractile, and structural properties of the atria have been called "atrial remodeling." The resulting electrophysiological substrate is characterized by shortening of atrial refractoriness and reentrant wavelength or by local conduction heterogeneities caused by disruption of electrical interconnections between muscle bundles. Under these conditions, ectopic activity originating from the pulmonary veins or other sites is more likely to occur and to trigger longer episodes of AF. Many of these alterations also occur in patients with or at risk for AF, although the direct demonstration of these mechanisms is sometimes challenging. The diversity of etiological factors and electrophysiological mechanisms promoting AF in humans hampers the development of more effective therapy of AF. This review aims to give a translational overview on the biological basis of atrial remodeling and the proarrhythmic mechanisms involved in the fibrillation process. We pay attention to translation of pathophysiological insights gained from in vitro experiments and animal models to patients. Also, suggestions for future research objectives and therapeutical implications are discussed.
What are the changes in the atria?
Aging, neurohumoral activation, and chronic atrial stretch due to structural heart disease activate a variety of signaling pathways leading to histological changes in the atria including myocyte hypertrophy, fibroblast proliferation, and complex alterations of the extracellular matrix including tissue fibrosis.
What is AF in a patient?
Atrial fi brillation (AF), the most common sustained cardiac ar rhythmia, is becoming progressively more prevalent with population aging. 1 Enormous advances in the understanding of AF pathophysiology have occurred over the past 20 years. 2, 3 The present article, part of a thematic series in Circulation on AF, provides a broad overview of AF pathophysiology and the potential implications for AF management. In addition, it furnishes background information on basic mechanisms relevant to other articles in the series dealing with AF epidemiology and genetics, stroke prevention, rate control therapy, sinus rhythm maintenance pharmacotherapy, management in structural heart disease, and catheter ablation. For more comprehensive treatment of specific mechanisms, the reader is referred to detailed review articles. 2 – 5
How is AF maintained?
AF can be maintained by reentry and/or rapid focal ectopic firing ( Figure 1 ). 2 The mechanism maintaining AF is often called the driver. The irregular atrial discharge typical of AF may result from an irregular atrial response to a rapidly discharging regularly firing driver resulting from either local ectopic firing ( Figure 1 A) or a single localized reentry circuit ( Figure 1 B). Alternatively, fibrillatory activity may be caused directly by multiple functional reentry circuits varying in time and space ( Figure 1 C).
How does reentry maintain AF?
Reentry can maintain AF by producing a rapidly firing driver with fibrillatory propagation ( Figure 1 B) or by producing multiple irregular reentry circuits ( Figure 1 C). Reentry can be conceptualized as either a leading circle ( Figure 3 A) or a spiral wave ( Figure 3 B). The maintenance of continuous activity in both models depends on atrial (substrate) properties, with an appropriate balance between refractory and excitability determinants. There are subtle but important distinctions between predictions of the models. 15 In the leading-circle model, reentry circuits spontaneously establish themselves in a circuit length (the wavelength [WL]; Figure 3 C) given by the distance the impulse travels in 1 refractory period (RP), given by the following equation: WL=RP×CV, where CV is the conduction velocity. 4, 15 The shorter the wavelength is, the larger the number of simultaneous reentry circuits that the atria can accommodate is ( Figure 3 D); increasing wavelength reduces the number of possible circuits ( Figure 3 E). Consequently, shortened RP and reduced CV promote reentrant AF, and drug-induced RP prolongation suppresses AF. Reduced RP also promotes spiral-wave reentry by accelerating and stabilizing spiral-wave rotors. 15 Either model explains AF occurrence with APD shortening, like familial AF caused by gain-of-function K + channel mutations and the antiarrhythmic effects of APD-prolonging drugs. 16 The efficacy of Na + channel blockers in AF runs contrary to leading-circle predictions but is well explained by the spiral-wave model. 15, 16 The AF-promoting effects of CV slowing with loss-of-function Na + channel and connexin mutations 3 are more easily understood with the leading-circle model.
How long does it take for AF to end?
AF often initially presents in a paroxysmal form, defined by self-termination within 7 days. Persistent AF requires termination by pharmacological or direct-current electric cardioversion. In permanent AF, restoration to sinus rhythm is impossible or judged to be inadvisable. Paroxysmal AF usually involves a driver in the cardiac muscle sleeve around ≥1 pulmonary veins (PVs) caused by rapid focal activity or local reentry. 6 It is believed that in many cases the natural history of AF involves evolution from paroxysmal to persistent to permanent forms through the influence of atrial remodeling caused by the arrhythmia itself and/or progression of underlying heart disease. 7, 8 AF-related electric remodeling, resulting from altered expression and/or function of cardiac ion channels, favors the development of functional reentry substrates, 7 which are reversible on AF termination (reverse remodeling) and contribute to persistent AF. As atrial disease progresses to irreversible structural changes, AF becomes permanent. 7, 9 Whereas 90% of paroxysmal AF is driven by PV sources and responds well to PV-directed ablation procedures, as AF progresses, atrial substrates become more complicated and require more complex ablation procedures. 10 The distinction between paroxysmal and persistent AF can be difficult. Although most recent-onset AF spontaneously terminates within 24 to 48 hours, physicians often decide to terminate AF earlier by pharmacological or electric conversion. Because it is unknown in such cases whether AF would have converted spontaneously, accurate classification is, strictly speaking, impossible. This uncertainty can potentially affect the reliability of clinical trial data.
Which muscles are focal triggers?
Right atrial structures like the vena cavas and crista terminalis can also provide focal triggers. 41 Pectinate muscles contribute to wave breakup and fibrillatory activity 42 and may act as anchor points for reentry. 43
What are the properties of cardiac cells?
RP is roughly defined by the time between initial cell firing and repolarization back to a value of −60 mV ( Figure 4 A). Increased inward currents (Ca 2+ and Na +) prolong APD, whereas enhanced outward currents (carried by K +) repolarize the cell and shorten APD. The determinants of CV include phase 0 inward currents (particularly Na +) that provide energy for conduction and gap junction connexin channels, which allow electric flow between cardiomyocytes ( Figure 4 B). Increased K + currents or decreased Ca 2+ currents shorten APD and promote reentrant AF; K + current blockade increases APD and suppresses AF. Reduced Na + current and connexin dysfunction promote AF by slowing conduction.
Who funded the research for AF?
AstraZeneca funded research on a remodeling-preventing drug by Dr Nattel. Dr Nattel served on the advisory boards for Xention, Merck, and Pierre-Fabre. The Montreal Heart Institute/Université de Montréal a patent for statins to prevent AF (inventor, Dr Nattel).
What are the cellular electrophysiological changes typifying AF?
The cellular electrophysiological changes typifying AF are a decrease in AP duration and depression of the AP plateau (Figure 2 ). These occur in pacing-induced AF in animals 6061 and in AF in patients. 62 A critical component of the cellular electrophysiological changes is altered restitution of AP duration, so that the response to rapid changes in rate is attenuated and vulnerability to the propagation of premature depolarizations is increased. 61 Abnormalities in calcium handling as described above are important contributors to this altered restitution. In the setting of chronically diseased and dilated atria, decreases in resting potential and in AP upstroke velocity occur as well. 28
What are the triggers of AF?
Triggers include sympathetic or parasympathetic stimulation, bradycardia, atrial premature beats or tachycardia, accessory AV pathways, and acute atrial stretch. Recently identified as triggers are ectopic foci occurring in “sleeves” of atrial tissue within the pulmonary veins or vena caval junctions. These regions likely resemble the juxtaposed islets of atrial myocardium and vascular smooth muscle in coronary sinus and AV valves that, under normal circumstances, manifest synchronous electrical activity but develop delayed afterdepolarizations and triggered activity on rapid pacing or acute stretch. 15 Supporting this idea are clinical studies of impulses generated by single foci propagating from individual pulmonary veins or other atrial regions to the remainder of the atria as fibrillatory waves 16 and abolition of AF by radiofrequency ablation to isolate the venous foci. 17
How long does it take for a goat to apoptosis?
Although there is no apoptosis in the goat model after 19 to 23 weeks of AF, 58 small numbers of apoptotic cells are identifiable in chronically fibrillating human atria. 59 These cells are likely to be lost structurally and functionally when apoptosis is complete, causing irreversible atrial damage.
What are the most common causes of AF?
In the West, about 5% of the population >65 years of age is afflicted with AF. 45 The most frequent causes of acute AF are myocardial infarction (5% to 10% of patients with infarct) 67 and cardiothoracic surgery (up to 40% of patients). 8 The most common clinical settings for permanent AF are hypertension and ischemic heart disease, with that subset of patients having congestive failure being most likely to experience the arrhythmia. In the developing world, hypertension and rheumatic valvular (usually mitral) and congenital heart diseases are also common associations. 91011
Can AF be converted to sinus rhythm?
Moreover, AF initially responsive to pharmacological or electrical cardioversion tends to become resistant and cannot then be converted to sinus rhythm. To some extent, the failure of the physician to suggest or the patient to accept further cardioversion attempts may lead to diagnosis of “permanent” AF.
What is AF in cardiology?
Atrial fibrillation (AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological alterations promoting AF have been studied extensively in animal models. Atrial tachycardia or AF itself shortens atrial refractoriness and causes loss of atrial contractility. Aging, neurohumoral activation, and chronic atrial stretch due to structural heart disease activate a variety of signaling pathways leading to histological changes in the atria including myocyte hypertrophy, fibroblast proliferation, and complex alterations of the extracellular matrix including tissue fibrosis. These changes in electrical, contractile, and structural properties of the atria have been called “atrial remodeling.” The resulting electrophysiological substrate is characterized by shortening of atrial refractoriness and reentrant wavelength or by local conduction heterogeneities caused by disruption of electrical interconnections between muscle bundles. Under these conditions, ectopic activity originating from the pulmonary veins or other sites is more likely to occur and to trigger longer episodes of AF. Many of these alterations also occur in patients with or at risk for AF, although the direct demonstration of these mechanisms is sometimes challenging. The diversity of etiological factors and electrophysiological mechanisms promoting AF in humans hampers the development of more effective therapy of AF. This review aims to give a translational overview on the biological basis of atrial remodeling and the proarrhythmic mechanisms involved in the fibrillation process. We pay attention to translation of pathophysiological insights gained from in vitro experiments and animal models to patients. Also, suggestions for future research objectives and therapeutical implications are discussed.
What is AF in medical terms?
Atrial fibrillation ( AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological al...
Why do myocytes move in the PV?
In theory, rapid activity in the PV area might result from new impulse formation due to automaticity or triggered activity or from (micro-)reentry due to abnormalities in tissue structure . An argument favoring automaticity is that during embryonic development, some markers, in particular HNK-1 (51, 268), are expressed in areas which will later form the conduction system and nodal tissue as well as in the PV region. However, by all accounts, the PVs in the adult heart consist mainly of myocytes morphologically very similar to normal atrial myocytes. Thus the PVs probably do not harbor large areas of hidden nodal tissue. There are diverging reports about the occurrence of abnormal myocytes scattered throughout the myocardial sleeves. Using electron microscopy, Masani (368) observed small, pale myocytes resembling nodal P cells in normal rat PVs. In normal dog PVs, no evidence for morphologically abnormal myocytes was found in two studies (241, 585), whereas large PAS-positive cells (i.e., cells with a high glycogen content) were found in another (110). In an electron microscopy study on human PVs, Perez-Lugones et al. (447) have reported the presence of nodal-like P cells, transitional cells, and large Purkinje-like myocytes in patients with a history of AF. These cell types were not present in PVs from patients without a history of AF (447). However, this study has engendered criticism of the histological technique itself and of the use of purely histological criteria to classify electrical phenotypes of myocytes (12). Recently, Morel et al. (391) have demonstrated the presence of small Cajal-like cells in the interstitium of human PVs. Similar cells are involved in pacemaking in the intestine, but their role in PV automaticity is unclear, and their presence has also been demonstrated in normal atrial myocardium (235). The contribution of scattered abnormal cell types with possible pacemaking properties remains to be established. In general, a certain critical size is required for an ectopic focus to act as a driver for the surrounding myocardium (269). Propagation from an ectopic focus is most likely when electrical coupling gradually increases from the focus to the surrounding muscle, because a high degree of electrical coupling would effectively silence the focus (reviewed in Ref. 270). Interestingly, a recent study has indicated that at the PV-left atrial junction, large PAS-positive myocytes expressing the pacemaker channel protein HCN4, are more separated by fibrosis and inflammatory infiltrates in chronic AF patients than in sinus rhythm patients (415).
What is the shape of the atrial action potential?
The predominant shape of the atrial action potential is triangular with a gradual repolarization phase as shown in the top right inset in Figure 2. If a plateau is present, it is less pronounced than in ventricular myocytes. The left panel of Figure 2shows a human atrial action potential and its main underlying ionic currents. As in ventricular myocytes, the main depolarizing currents are the rapidly activating and inactivating Na+-current (INa) and the L-type Ca2+current (ICaL), which has somewhat slower kinetics. The differences in action potential morphology between atria and ventricles are mainly caused by differences in ion channel current density and kinetics of repolarizing currents. Some types of ion channels are selectively expressed by atrial myocytes. Atrial-specific ion channels represent interesting targets for cardioversion of AF (160), given the risk for ventricular proarrhythmia of traditional class I drugs (reduction of excitability and conduction velocity, mainly by sodium channel blockade) and class III drugs (prolongation of refractoriness, mainly by potassium channel blockade) (465).
What are the most common causes of AF?
Hypertension is found in 60–80% of AF patients (396). Hypertension is an independent predictor of AF (581), and it contributes to AF progression. Vascular disease, and most notably coronary artery disease, is found in one-fourth to one-third of AF patients in surveys (396, 416), and may be associated with AF-related complications (255). Heart failure with dyspnea on exertion (NYHA classes II-IV) is found in 30% of AF patients (416), and AF is found in 30–40% of patients with heart failure (115). Heart failure and AF appear to promote each other, with AF compromising LV function, and LV dysfunction causing atrial dilation and pressure overload. Valvular heart disease, especially mitral valve disease, was the most common clinical condition associated with AF 50 years ago. Early antibiotic therapy of streptococcal infections has markedly reduced severe mitral valve disease in more recent surveys (396, 416). These conditions are associated with atrial dilatation, which plays an important causative role in the development of a substrate of AF (sects. IVand V). Diabetes mellitus is one of the established risk factors for stroke in AF patients (190) and is found in ∼20% of all patients with AF (396, 416). The high prevalence of diabetes mellitus in AF populations suggests that diabetes may either cosegregate with AF due to similar conditions that cause both AF and diabetes, or may imply that diabetes mellitus plays a causative role in the occurrence of AF. Thyroid dysfunction, and especially hyperthyroidism, is also associated with AF. Adequate therapy of thyroid disease often terminates AF. Improved clinical management of thyroid disease has rendered thyroid dysfuction relatively rare in current AF populations (416).
What are the factors that contribute to the progression of AF?
1B) contribute to a gradual and progressive process of atrial remodeling characterized by changes in ion channel function, Ca2+homeostasis, and atrial structure such as cellular hypertrophy, activation of fibroblasts, and tissue fibrosis. These alterations may both favor the occurrence of “triggers” for AF that initiate the arrhythmia and enhance the formation of a “substrate for AF” that promotes its perpetuation. The association of clinical factors with AF substrates and triggers will be discussed separately.
How is AF perpetuated?
In general, AF can be perpetuated by “hierarchical” or “anarchical” mechanisms. In case of a hierarchical organization of AF, the arrhythmia is driven by a rapid localized source. As the atrial myocardium remote from this site cannot follow the driver in a 1:1 fashion, irregular conduction at a lower frequency ensues.
How does AF affect haemodynamics?
AF adversely affects cardiac haemodynamics because of loss of atrial contraction and the rapidity and irregularity of the ventricular rate. AF causes significant symptoms in approximately two thirds of patients. AF is associated with a 1.5- to 2-fold increase in mortality.
What is the pathogenesis of AF?
The pathogenesis of AF is now thought to involve an interaction between initiating triggers, often in the form of rapidly firing ectopic foci located inside one or more pulmonary veins, and an abnormal atrial tissue substrate capable of maintaining the arrhythmia. Although structural heart disease underlies many cases of AF, the pathogenesis of AF in apparently normal hearts is less well understood. Although there is considerable overlap, pulmonary vein triggers may play a dominant role in younger patients with relatively normal hearts and short paroxysms of AF, whereas an abnormal atrial tissue substrate may play a more important role in patients with structural heart disease and persistent or permanent AF.
How many patients were enrolled in the AFFIRM study?
15 The study enrolled more than 4000 patients with predominantly persistent AF. Enrolled patients (mean age 70 years) had at least one risk factor for stroke or death accompanying AF and could symptomatically tolerate the arrhythmia at baseline. Approximately 50% of patients randomised had a history of hypertension, whereas 25% had coronary artery disease or heart failure. Patients randomised to rate control received digoxin, β blockers, or calcium antagonists, whereas those randomised to rhythm control received amiodarone, sotalol or propafenone and, if necessary, DC cardioversion. At follow up, sinus rhythm was achieved in only 60% of patients in the rhythm arm, whereas satisfactory rate control was achieved in 80% of patients in the rate control arm. The primary end point of the study, all cause mortality, was not significantly different between the two groups, although there was a trend favouring rate control. There were also no differences in secondary end point components, including stroke rate, quality of life, or functional status and, although a trend favouring rate control was once again noted, anticoagulation was discontinued in more patients in the rhythm than in the rate control group. The majority of strokes in both groups occurred in patients with subtherapeutic levels of anticoagulation, or after warfarin had been stopped. In the pre-defined group of patients who were under the age of 65, which accounted for approximately a quarter of patients included in the study, a trend favouring rhythm control was noted.
What is the term for AF?
Temporal classification of atrial fibrillation (AF). An incident episode of AF presenting to medical attention may be the first ever detected episode of the arrhythmia, or represent recurrence of previously recognised arrhythmia (left). The episode may prove to be self terminating (paroxysmal), persistent (continuing until medical intervention such as DC cardioversion), or permanent (continuing for longer than one year or despite medical intervention such as DC cardioversion) (right).
How long before cardioversion for AF?
For patients who have been in AF for longer, or in whom the duration of the arrhythmia is not clear, a minimum period of anticoagulation of three weeks is recommended before cardioversion. 1 An alternative approach, particularly useful if there is clinical urgency to restore sinus rhythm, is to perform transoesophageal echocardiography in an attempt to exclude the presence of atrial thrombus before cardioversion. However, even if transoesophageal echocardiography has demonstrated no thrombus before cardioversion, patients must be anticoagulated for at least one month after cardioversion, since mechanical atrial function may return slowly after cardioversion.
What is AF in medical terms?
Classification, pathophysiology, and mechanisms of AF: key points. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. AF is usually classified according to its temporal pattern as paroxysmal, persistent, or permanent. AF adversely affects cardiac haemodynamics because of loss of atrial contraction and ...
How does persistent AF work?
Both experimental and human mapping studies have demonstrated that persistent AF is generally characterised by the presence of multiple wavelets of excitation that propagate around the atrial myocardium. However, there is considerable variability in the observed patterns of activation, both between patients and between the two atria of individual patients. Perpetuation of AF is facilitated by the existence or development of an abnormal atrial tissue substrate capable of maintaining the arrhythmia, 6 with the number of meandering wavelets that can be accommodated by the substrate determining the stability of AF. 7,8 Re-entry within the atrial myocardium is facilitated by conduction slowing and shortening of the refractory period. Both have been demonstrated in animal models and patients with AF, with increased dispersion of refractoriness further contributing to arrhythmogenesis. Shortening of the atrial action potential, reduced expression of L type calcium channels, and microfibrosis of the atrial myocardium have also been demonstrated.
What happens to the body during anaphylactic shock?
During anaphylactic shock, your body goes into overdrive by producing inflammatory chemicals to attack the allergen. In turn, this acute response affects other parts of your body, too. Learn more about the symptoms that occur during anaphylaxis as well as the overall effects on your body. Anaphylaxis isn’t the same as allergies, ...
How does anaphylaxis affect the immune system?
But with anaphylaxis, your immune system has an exaggerated response when you’re exposed to the substance again. This response affects the whole body and may put your life in danger. Symptoms may begin within seconds.
Why do you need adrenaline injections for anaphylaxis?
In anaphylaxis, an extra dose can help increase blood flow throughout your body and help reverse the immune system’s aggressive response. This is why your doctor will recommend adrenaline (epinephrine) injections in the case of anaphylaxis. It will stop the inflammation from spreading to other body systems.
What happens when you get antigens?
Sometimes, when your body encounters that antigen again, your immune system overreacts. Far too much histamine and other inflammatory chemicals are quickly released into your system. This leads to a wide variety of symptoms throughout the body. It can quickly turn into a medical emergency.
What does the immune system do?
Your immune system fights antigens like bacteria, viruses, and fungi. It learns to recognize these harmful substances and works to neutralize them. Once your immune system#N#Trusted Source#N#interacts with an antigen, it stores the information for future use. When it’s doing its job, you don’t get sick.
What happens when you have anaphylaxis?
During anaphylaxis, small blood vessels (capillaries) begin to leak blood into your tissues. This can cause a sudden and dramatic drop in blood pressure. Other symptoms include a rapid or weak pulse and heart palpitations.
Why is prompt treatment important for anaphylaxis?
slurred speech, hoarse voice, and difficulty talking. As your body goes into shock, loss of consciousness occurs. This is why prompt treatment and medical attention are vital to preventing possible complications of anaphylaxis. Last medically reviewed on June 21, 2018.
Why is understanding the pathophysiological mechanisms behind different toxic agents important?
Understanding the pathophysiological mechanisms behind different toxic agents has important implications for the classification of toxic agents, determining the safe exposure levels and identification of antidote treatments.
How do organophosphates affect the nervous system?
The organophosphates exert their main toxicological effects through irreversible phosphorylation of cholinesterase in the central nervous system [ 3, 4 ]. The acute toxic effects are related to irreversible inhibition of acetylcholinesterase [ 4 ]. Organophosphates are substrate analogues to acetylcholine, and like natural substrate enter the active site covalently binding to the hydroxyl group on the cholinesterase enzyme. Organophosphate is split and the enzyme is phosphorylated. While the acyl enzyme is quickly hydrolysed to regenerate the free enzyme, dephosphorylation is very slow (on the order of days), and phosphorylated enzyme cannot hydrolyze the neurotransmitter [ 5 ]. The inhibition of the enzyme leads to accumulation of ACh in the synaptic cleft resulting in excessive stimulation of the nicotinic and muscarinic cholinergic receptors and resultant defective neurotransmission. The typical symptoms of acute organophosphate poisoning are agitation, muscle weakness, muscle fasciculation, miosis, hypersalivation and sweating. Higher doses may cause respiratory failure, unconsciousness, confusion, convulsions and death.
How does poisoning affect the cell?
Poisoning involves delivery of toxic substance to its target. The toxic agent interacts with some endogenous molecules that may trigger interruption in function or structure of a cell. It may initiate repair mechanisms at the molecular, cellular, and/or tissue levels. An understanding of pathophysiology of toxic agent provides a rational basis for interpreting descriptive toxicity data. The various cellular mechanisms that contribute to the manifestation of toxicities can be related to a series of events that begins with exposure, interaction between toxic agent and the endogenous molecules, and finally the toxic effect.
Is aluminium phosphide toxic?
The toxicity of aluminium phosphide is attributed to the liberation of phosphine gas, a compound that causes ROS (reactive oxygen species) mediated injury to the cells, inhibits vital cellular enzymes and is directly corrosive to tissues.
Introduction
Tissue Mechanisms and Clinical Presentation
Basic Arrhythmia Mechanisms
Atrial Remodeling
Anatomic Factors
Contractile Considerations
- AF and Ventricular Function
Atrial contraction contributes ≈20% of left ventricular stroke volume at rest48; this contribution is lost in AF. In addition, AF may cause left ventricular dysfunction as a result of inappropriately rapid49 and/or irregular50 ventricular rhythms (Figure 7). Coronary flow reserve may also be ne… - Ventricular Function and AF Risk
Congestive heart failure increases AF prevalence.54 AF promotion occurs through factors that facilitate both reentry and ectopic firing, including fibrosis, cell stretch, impaired Ca2+ handling, and ionic current remodeling.2–5,13,21
Thromboembolic Determinants
Management Implications
The Future of Translational Research on Af Mechanisms
Sources of Funding