Introduction

Reentry describes a self-sustaining cardiac rhythm abnormality. In reentry, the action potential propagates in a circus-like closed loop manner. It is a disorder of impulse conduction and thus describes one kind of arrhythmogenesis and is differentiated from disorders of impulse generation such as automaticity and triggered activity. First studies investigating reentry are over 100 years old and go back to Mines and Garrey.[1][2][3] Dysrhythmias based on the reentry mechanism include atrial tachyarrhythmias such as atrial flutter (AFlut), atrioventricular nodal reentry (AVNRT), atrioventricular reentry (AVRT) like Wolff-Parkinson-White (WPW) syndrome and ventricular reentry such as bundle branch reentry (BBR). The pathophysiologic importance of reentry and utility as a treatment target in atrial fibrillation (AFib) is part of ongoing research.

The main task of the heart is to produce cardiac output. Therefore myocardiocytes contract in a highly orchestrated and rhythmic manner. Proper electro-mechanic coupling (EMC) translates electric stimulation into contraction. The action potential runs from the sinus node (SN) via right atrial pathways through the atrioventricular node (AVN) and the His bundle down the Purkinje fibers (His-Purkinje system, HPS) to the ventricular myocardium. Cells are either in an excited or resting condition. From the resting potential, the cell is depolarized until the crossing of a critical threshold, which then causes an action potential (AP). Following the action potential, there is a period of refractoriness (refractory period, RP) when another trigger cannot activate the cell. Wavelength (WL) or cycle length (CL) is the time between two action potentials.

Etiology

The etiology of reentry is diverse and includes:

• Electrolyte abnormalities and channelopathies form a substrate for reentry arrhythmias.
• A mechanical force such as the chest thump maneuver induces but also terminates reentry.[4]
• Chronic cardiac stretch leads to remodeling and fibrosis that changes electrical properties of the myocardiocytes.
• Scar tissue following infarction is the basis of anatomical reentry.
• Congenital heart disease and surgery performed to treat it can cause reentry.
• Genetic culprits are related reentry tachycardias. Roberts et al. identified genetic culprits SCN5A and LMNA as a cause of idiopathic bundle branch reentry ventricular tachycardia.[5]

The connection between congenital heart disease and reentry is of particular research interest and requires further attention. Congenital heart disease itself or scars following surgical repair poses a substrate for reentry circuits.[6] Patients with Ebstein anomaly are prone to supraventricular tachyarrhythmias because of multiple accessory pathways.

Muscular bridges crossing the fibrous atrioventricular skeleton can cause the Wolff-Parkinson-White syndrome in Ebstein patients.[7] Surgical procedures known to cause arrhythmias due to reentry include the Mustard Senning procedure for transposition of the great arteries or the Fontan Bjork operation for a univentricular heart.[8] Pericaval intra-atrial reentry tachycardia (IART) is specific to Fontan surgery with longer cycle lengths and zones of slow conduction compared to periannular IART. Both, pericaval und periannular IART are amenable to ablation.[9] Ventricular tachycardia following repair of congenital heart disease can be traced to anatomic isthmuses and thus be successfully ablated.[10]

Arrhythmogenic right ventricular dysplasia has characteristic fibrofatty atrophy of the right ventricular myocardium and accompanying ventricular arrhythmias. Ellison et al. described clustering of reentry circuits sites in areas like the right ventricular outflow tract and the tricuspid annulus that are affected by fibrotic changes.[11][12]

Epidemiology

As a pathophysiologic mechanism of arrhythmias, the incidence and prevalence depend on the arrhythmia ranging from highly prevalent diseases like atrial fibrillation to rare diseases like Wolff-Parkinson-White atrioventricular reentry tachycardia. Atrial fibrillation occurs in 10% of the over 60-years old. In patients undergoing surgery for mitral valve disease, it can be found in 60% of the cases. Atrial fibrillation is associated with increased mortality due to three problems: thromboembolism causing stroke, decreased cardiac output due to atrioventricular synchrony, and irregular heartbeat.[13] Ventricular tachyarrhythmias can cause sudden death in patients suffering from chronic heart failure.[14] 15% of adult patients with congenital heart disease have concomitant supraventricular tachycardias (SVT).[8]

Regarding the epidemiology of SVT, the AHA/ACC/HRS guideline from 2015 reports a prevalence of 2.29 per 1000 persons, an incidence of 36 per 100.000 persons per year and approximately 89.000 new cases per year and 570.000 people living with SVT. AVNRT is more common in middle-aged or older person, whereas AVRT is more prevalent in adolescents. ECG changes due to WPW syndrome can be found in 0.1 to 0.3% of the population.[15]

Pathophysiology

The study of arrhythmogenesis comprises disorders of impulse initiation and disorders of impulse conduction. Impulse initiation disturbances include automaticity and triggered activity with early and late depolarizations (EAD and DAD). Automaticity is the spontaneous depolarization of tissue which is physiologic in the sinus and atrioventricular node and the His bundle. This is in contrast to triggered activity, which is abnormal impulse generation in response to a previous stimulus.

Arrhythmias caused by early depolarizations include Torsade de Pointes and delayed depolarizations are exemplified by ventricular arrhythmia due to digitalis toxicity. Reentry is a mechanism of pathologic impulse conduction. Reentry is connected to structural heart disease whereas automaticity and triggered activity may be found in structurally normal hearts.[16]

Computer simulations play an essential role in electrophysiology research. Liu et al. used computer simulation to show that delayed after-depolarizations, which are spontaneous depolarization occurring late during an action potential, can trigger premature ventricular complexes (PVC) and in vulnerable tissue with properties of unidirectional block can cause reentry. This is called triggered activity with reentry.[17] As a general rule, it is possible to say that reentry is responsible for ventricular tachyarrhythmias following myocardial infarction, whereas automaticity and triggered activity lead to arrhythmia in chronic heart failure.[14]

Mines described three criteria to define reentry. For reentry to occur unidirectional block, return to point of origin and the possibility to interruption are required.[18] Heterogeneity of structural and electrophysiological properties increases the likelihood of unidirectional block and thus creates fertile ground for reentry.[19] 

The wavelength of the reentry circuit is defined by the impulse conduction velocity times the refractory period.[20] Rensma et al. studied the characteristics of wavelength conduction velocity and the refractory period required to initiate atrial flutter and fibrillation. They showed that wavelength is the best predictor for inducibility of arrhythmias.[21]

Mechanic and electric properties of the cell are interdependent, which is called the mechanoelectrical feedback (MEF) or electrochemical coupling (ECC). Acute stretch induces cell currents causing depolarization (stretch-activated currents, SAC).[4] Regarding the physiologic mechanism, an acute stretch during systole shortens the action potential and the refractory period, and thus the wavelength which in general favors reentry. Chronic stretch leads to fibrosis and subsequently to different conduction across longitudinal and perpendicular cell axis, which is called anisotropy and leads to zig-zag conduction across cells.[22] 

Gilmour et al. studied the electrophysiological mechanisms giving rise to reentry in a ring-like Purkinje muscle junction model. They imitated conditions that are present in the ischemic heart by chemically creating a unidirectional block, shortening the action potential duration, which finally initiated reentry. Furthermore, they described the relation between Purkinje fibers and muscle cells as source and sink, respectively. Asymmetrical impulse transmission, which can be found in the heart due to anisotropy, contributes to arrhythmia. Dispersion of refractoriness due to different membrane properties and cell coupling also plays a role in reentry mechanism.[23]

There are many concepts of functional reentry such as the leading circle reentry,[24] the spiral rotor wave, phase 2 reentry, and figure of eight reentry.

Comtois introduced the idea of spiral wave reentry. The spiral wave reentry is a continuously rotating electric potential around a point of phase singularity where wavetail and wavefront meet. It can be evaluated by dominant frequency analysis and complex fractionated electrogram (CFE).[25] Spiral wave reentry is the proposed mechanism for VF and polymorphic VT.[16][26][27]

Antzelevitch et al. observed differences in action potentials at different epicardial sites giving rise to reentry. The transmural voltage gradient is visible on electrocardiogram (ECG) as j-wave or st-segment elevation. Since these changes are related to the second phase of the action potential, this is called phase 2 reentry.[28] The concept of phase 2 reentry has been proposed by Lukas et al. and is connected to the syndromes of Brugada and early repolarization.[29][16]

The multiple wavelet theory was first proposed by Moe in 1959 researching the pathophysiologic basis of atrial fibrillation. This theory states that many wavefronts will not die out spontaneously. This idea found reinforcement with Allessie's finding that four to six simultaneous reentrant wavelets are needed to maintain atrial fibrillation.[20][30] Yagishita described localized reentry in atrial fibrillation and the difficulty to differentiate it from focal activation.[31]

Different mechanisms of arrhythmogenesis may be responsible for initiating and sustaining atrial fibrillation. Accepting the multiple wavelet theory as the sustaining force, Haissaguerre described ectopic foci at the point where the pulmonary veins insert into the left atrium for initiation of atrial fibrillation. This allowed for targeted radiofrequency ablation.[32] Pulmonary vein ectopic foci show high dominant frequency giving origin to fractionated rotors.[33] In some patients, both atrial fibrillation and atrial flutter can occur. This clinical interrelationship may reflect an underlying common pathophysiology such as atrial fibrillation can cause a functional line of block that creates a macro-reentrant circuit and atrial flutter. On the other side atrial flutter, due to short cycle length may result in atrial fibrillation.[34]

Histopathology

Reentry around an anatomical obstacle has been named anatomic reentry as compared to functional reentry. Cox et al. who developed the surgical treatment for atrial fibrillation observed that chronic atrial enlargement causes atrial fibrillation. The concept of the "two holes macro-reentry" including the left atrial appendage and the pulmonary vein orifice led to the idea of creating lesions to interrupt these anatomical reentry circuits.[13] Myocardial scars following infarction may serve as an anatomic obstacle around which a reentry circuit can form.[35] The joint ESC/NASPE expert group proposed according to Cosio the term macro-reentrant tachycardia (MRT) to describe many reentrant tachycardias around a large central obstacle. Typical atrial flutter is the most common MRT. Lower loop reentry around inferior vena cava is a variation of typical atrial flutter and upper loop reentry around superior vena cava.[36] Other examples of anatomic reentry include scar-related VT and BBRVT.

Identifying parts of the reentry circuit is essential for successful ablation maneuvers to terminate the arrhythmia.[37] The right atrium possesses the anatomical structures that form the atrial flutter circuit.[38][39] The cavotricuspid isthmus (CTI) is the narrow point between the inferior vena cava and the tricuspid annulus where typical atrial flutter can undergo ablation successfully.[40] Anatomical reentry in cases of atrial flutter can also form around barriers such as the crista terminalis, eustachian valve, inferior vena cava, coronary sinus, and tricuspid annulus.[41] A circuit inside the CTI may serve as reentry circuit known as intra-isthmus reentry.[42][43][44] The terminal crest has anisotropic property and forms a functional line of a block to conduction in the right atrium.[45][46]

Left atrial macro-reentry circuits have also been described. The Bachmann bundle is a large muscle bundle that conducts excitation under physiologic conditions from the right atrium to the left.[47][48] Macro-reentry circuits include the mitral isthmus and epicardial connections located in the ligament of Marshall known as the Marshall bundle causing peri-mitral atrial tachycardia (PMAT). Peri-mitral atrial tachycardias develop following pulmonary vein isolation (PVI) or mitral valve surgery.[49][50] There have also been reports of reentrant atrial tachycardia not involving the AV node. Adenosine-sensitive atrial tachycardia has variable locations and can shift to another site after ablation. In a case reported by Inagaki mapping identified the critical slow conduction zone close to the mitral annulus.[51]

The fibrous skeleton of the heart plays a role as electric insulation between atria and ventricles.[7] Usually, the AV node connects to the His bundle form the only electric connection between atria and ventricles. 60% of paroxysmal supraventricular tachycardias are AVNRT.[52] The dual pathway model of the AV node as proposed by Mendez et al. forms the pathohistological basis for AVNRT. According to this model, the upper part of the AV node comprises two pathways, an inferior-slow (shorter ERP but longer AV delay) and superior-fast (longer ERP but shorter AV delay) pathway, providing input to the His bundle. If transverse propagation fails, longitudinal propagation occurs. The transverse-versus-longitudinal electrical propagation inside the AV node results in dissociation in the distal node and dual input into the His bundle, a phenomenon described as His electrogram alternans. AVNRT uses these different pathways inside the AV node as reentry circuit. This also offers a target for successful ablation of AVNRT.

Electrophysiologists prefer ablation of the slow pathway since ablation of the fast pathway poses a higher risk for AV block.[53] Localizing the slow pathway in an electrophysiologic study can be done through an anatomic approach according to Haissaguerre or using an assessment of potentials as was proposed by Jackman. The slow pathway is located at the atrial septum along the tricuspid annulus midway between the His bundle recording site and the coronary sinus ostium, and the fast pathway is located anteriorly near the His bundle.[54] Spach observed reentry due to anisotropy as cells conduct currents different depending on longitudinal or transversal axis. He challenged Moe's idea of anatomic slow and fast pathways of the AV node and made anisotropy responsible for AVNRT.[55]

Atrioventricular reciprocating tachycardias form a reentry circuit via the atrioventricular node/his Purkinje system and one or more accessory pathways. Accessory pathways bridges span the atrioventricular plane in addition to the physiological pathway via the atrioventricular node and his bundle. Wolff, Parkinson, and White described the first preexcitation syndrome in 1930. Atrial fibrillation may conduct via the accessory pathway instead of the av node bypassing the frequency limiting effect. This leads to a fast, broad and irregular tachycardia and rarely to ventricular fibrillation.[56]

The bundle branch reentry ventricular tachycardia (BBRVT) runs via a macro-reentry circuit including the His bundle and the fascicular branches. It is common in dilatative cardiomyopathy with reduced left ventricular ejection fraction. The right bundle branch is more vulnerable to unidirectional block due to a long refractory period and slow retrograde conduction via the left bundle branch. The connection between the two bundle branches forms by bridges spanning the ventricular septum. The surface electrocardiogram (ECG) will show a left bundle branch block (LBBB) pattern. The contrariwise BBRVT showing right bundle branch block (RBBB) pattern on ECG is rare.

Interfascicular tachycardia or left ventricular BBRVT includes antegrade conduction through the left-anterior and retrograde conduction via the left posterior fascicles, which manifests as right bundle branch block with left-posterior hemiblock on ECG. Criteria for the diagnosis of BBRVT through electrophysiologic examination include the following:

• LBBB pattern on ECG; slowed conduction of the His-Purkinje system
• Termination of BBRVT through blocking the His-Purkinje system proximal to distal activation of the His bundle and right bundle branch
• The His ventricular interval in BBRVT is equal or longer than the His ventricular interval in sinus rhythm
• Variations of the V-V interval that are preceded by variations of the H-H interval

BBRVT should be not inducible after ablation of the right bundle branch.[57][58][59][60]

In contrast to macro-reentry better resolution of mappings systems allowed to detect smaller reentry circuits, called localized reentry or micro-reentry. The resolution of mapping depends on the distance between electrodes, which is limited, per se. There is an ongoing debate about whether focal activity is micro-reentry. Some studies propose micro-reentry based on fractionated electrograms, areas of slow conduction or zig-zag pattern of activation. Ideker et al. estimated the electrode spacing needed to detect the smallest micro-reentry. Spach et al. described the smallest reentry circuit in superfused human atrial trabeculae spanning an area of 1.6 mm. Ideker argues that electrodes need not be as close together to register the reentry circuit just as a hurricane is noticeable from a great distance.[61]

El-Sherif illustrated the competing concept of disorders of impulse generation (rapid firing focus) against disorders of impulse conduction (reentry) using the clinical entity of SVT. He concludes that a rapid firing focus cannot be differentiated from a micro-reentry completely.[62] Garan and Ruskin induced myocardial infarction in animal experiments to study sustained monomorphic ventricular tachycardia with electrodes in proximity. They observed continuous electrical activity (CEA) in small areas of infarcted myocardium on the initiation, maintenance, and termination of VT. They interpreted these small locations of CEA as micro-reentry.[63] In a letter to the editor, Tai discusses a report of macro-reentrant interfascicular reentry with convincing data to exclude bundle branch reentry but not enough evidence to rule out micro-reentrant intra-fascicular reentry.[64]

History and Physical

Symptoms of SVT often start in young adulthood with a mean age of 32+-18 years for AVNRT compared to 23+-14 years for AVRT. Patients with AVNRT show a female predilection. Patients with SVT reported the following symptoms (% of cases): palpitations (22%), chest pain (5%), syncope (4%), and sudden cardiac death in (0.4%). Panic or anxiety may occur concomitantly. In AVNRT patients often complain about neck pounding, which may be attributed to cannon A waves. Higher right atrial pressure may lead to polyuria in AVNRT. Exertion or substances like coffee or alcohol can trigger AVNRT.[15]

Evaluation

To evaluate arrhythmias, different types of ECG (surface 12-lead, Holter, event recorder, intracardiac) and finally electrophysiologic studies using targeted stimuli are available. There are helpful ECG features to distinguish between AVNRT and AVRT. Features favoring AVRT include delta wave, lengthening of the tachycardia cycle length when bundle branch occurs ipsilateral to the accessory pathway, and the finding of QRS alternans. On the other hand features such as pseudo s in lead II or pseudo r' in lead V1 favor AVNRT.[41] The Brugada algorithm using the QRS morphology in the precordial leads and the Vereckei algorithm based on QRS changes in lead aVR assist in the differentiation between SVT and VT.[15]

The entrainment technique is required to diagnose reentry. It is useful to diagnose, ablate and map reentry. Mapping allows for identification of reentry circuit elements such as entry, exit, conduction barriers, bystanders, inner and outer loop, isthmus site, and zone of slow conduction (SCZ).[65][66] Stevenson et al. proposed a mapping site classification to guide ablation. Radiofrequency ablation success correlated with different locations in the reentry circuit. Successful ablation targets include zones of slow conduction (SCZ) and exit sites.[67][68][35] 

Waldo formulated three criteria for entrainment. These are fixed fusion with constant pacing rate, progressive fusion at faster pacing, and resumption of tachycardia with captured not fused beat on termination of pacing.[69][16] Waldos observation lead to prophylactic implantation of electrodes to terminate postoperative atrial flutter by overdrive pacing. The excitable gap is the part of the reentry circuit between the tail of refractoriness and the next orthodromic excitation wave. An external stimulus can enter the reentry circuit at the excitable gap.[70] Through entrainment Waldo et al. differentiate between atrial flutter type I and II. Atrial flutter type I can be transiently entrained and interrupted by rapid atrial pacing since it is caused by reentry and has an excitable gap. Type I atrial flutter can show concealed entrainment with a zone of slow conduction. In contrast, type II atrial flutter has not been entrained, and the mechanism remains speculative.[69]

To entrain the tachyarrhythmia the paced cycle length needs to be 10 to 20ms shorter than the tachycardia cycle length (TCL). A fusion beat is the appearance of a QRS complex being formed by the addition of a paced or premature stimulus and the physiologic action potential. Constant fusion, progressive fusion, and variable fusion can be distinguished.[71] Entrainment with fusion proves that reentry is the cause of the investigated arrhythmia. The PPI-TCL duration gives information whether the place of stimulation is inside our outside the reentry circuit. PPI response pattern characterizes different electrophysiologic properties of the tissues (excitable gap, excited tissue, refractory tissue).[72] Similarly, the stimulus to QRS interval can be used to assess lead placement relative to the reentry circuit.[73]

Electrophysiologic studies are indicated for supraventricular or ventricular tachycardias. Several measurements help to investigate the pathophysiologic mechanism of arrhythmias and might reveal reentry as a cause. The A-H jump, which is a sudden increase of the atrial-hisian interval to more than 50ms with a prior stimulus, indicates dual AV node physiology and together with inducible tachycardia suggest AVNRT.[74]

The Wolff-Parkinson-White (WPW) syndrome and Lown-Ganong-Levine (LGL) syndrome belong to the group of atrioventricular reentry tachycardias (AVRT). Depending on the direction the accessory pathway is used, orthodromic (antegrade conduction via AV node-His bundle and retrograde conduction via AP) or antidromic (retrograde conduction via AV node-His bundle and antegrade conduction via an accessory pathway) AVRT are differentiated. Accessory pathways are muscle bridges connecting the atria and the ventricle along the tricuspid and mitral annulus spanning the fibrous cardiac skeleton thus offering additional conduction routes beside the AV node-His bundle. Atrioventricular accessory pathways are called Kent bundles, and atriofascicular accessory pathways are called Mahaim fibers.[75][76] Antegrade AP conduction manifests in the ECG as Delta wave, short PQ interval, and QRS prolongation. But ECG manifestations may be discrete or hidden such as with posterior AP or retrograde conduction. Ablation is the recommendation when the refractory period is shorter than 250 ms and in cases of inducible AVRT or symptomatic preexcitation syndrome.

The surface ECG algorithm helps to localize the accessory pathway. A positive delta wave in V1 and negative in I and aVL proposes a left-sided (posterior) AP otherwise a right-sided AP. A positive delta wave in III and aVF indicates superior location, contrariwise inferior location. Right atrial septal AP show R/S ratio larger than one in V3 or earlier. If it is not the case, free wall AP should be suspected. 60% of APs are located at the left atrial free wall, 25% at the septum, and 15% right free wall.[56][[41] 

Veenhuyzen describes how to differentiate types of SVT such as AVNRT, AT and AVNRT using entrainment technique and observing manifest or concealed entrainment. Ventricular stimulation of SVT showing manifest entrainment suggests AVRT whereas ventricular stimulation of SVT showing concealed entrainment proposes AVNRT. The PPI-TCL is shorter in AVRT as compared to AVNRT. A post-pacing interval of A-A-V is specific for AT, whereas A-V indicates AVRT and AVNRT. The same applies to the atrial-hisian response. A-A-H response pattern indicates AT whereas A-H response pattern indicates AVRT or AVNRT. Concealed entrainment (AVNRT) is not the same as entrainment with concealed fusion (AVRT with pacing site close to AP). Entrainment pattern depends on the pacing site. Therefore, the response should be measured with different pacing locations (differential entrainment).[71]

Almendral examined resetting and entrainment phenomena in ventricular tachycardias. Resetting is the singular interaction between a stimulus and a given rhythm. Entrainment is the continuous resetting of the rhythm to repetitive stimuli. Almendral describes the concept of resetting a cardiac rhythm comparing the effect of a ventricular premature beat on continuous stimulation with V00 or VVI pacemaker. In V00 stimulation there will be no influence of the premature beat. Thus no resetting occurs. In contrast, in VVI the premature beat is sensed, a compensatory pause made, and thus the following stimuli are reset. Josephson described entrainment as the continuous resetting of a tachycardia.[77]

Treatment / Management

The AHA/ACC/HRS 2015 guideline makes recommendations on the treatment of SVT. Regular SVT should be treated with Valsalva maneuver and if unsuccessful with adenosine. If these fail or the patient is hemodynamically unstable cardioversion should be performed. Ongoing treatment includes beta blocker, calcium channel blockers, and sodium channel blockers, amiodarone or digoxin depending on the kind of SVT. The only curative treatment is ablation.[15]

The Sicilian Gambit proposes a rational approach to antiarrhythmic drug selection. In contrast to empiric drug choice, this approach tries to identify the underlying mechanism of arrhythmogenesis to target drug therapy. The common form AVNRT uses slow pathway in antegrade conduction and retrograde fast pathway excitation. First-line therapy is the vagal maneuver. Drugs of choice include adenosine, beta blockers such as esmolol, and calcium channel blockers such as verapamil or diltiazem. All these drugs affect the slow conduction pathway. To target the fast pathway sodium channel blockers and amiodarone can be used. In orthodromic WPW syndrome, the excitation travels the AV node antegrade and the accessory pathway Kent bundle retrogradely. The length of the excitable gap can be evaluated in electrophysiologic studies. If the reentry is associated with a short excitable gap, potassium channel blocking agents such as amiodarone can be used to lengthen the refractory period of the accessory pathway. If the reentry is associated with a long excitable gap a sodium channel blocker may be chosen.[75]

Atrial flutter is based on a macro-reentry mechanism. Antitachycardic pacing is an option to treat atrial flutter. Stimulating the right atrium for 20 to 30 seconds with a rate of 10 beats per minute higher than flutter and up to 400 beats per minute can terminate the flutter circuit. Otherwise, ablation of a narrow part of the reentry pathway such as the cavotricuspid isthmus (CTI) can erase the reentry arrhythmia.[78][79]

Liu et al. reported a case of multiple (in this case bilateral) accessory pathways and three different appearances of AVRT. Multiple accessory pathways are present in 15% of WPW cases. Different combinations of conduction result in different morphologies of AVRT in the same patient.[80] In general, type A preexcitation uses antegrade conduction via AV node and retrograde via an accessory pathway resulting in a narrow QRS complex and type B preexcitation antegrade via an accessory pathway and retrograde via AV node resulting in a broad QRS complex. Radiofrequency ablation has success rates of 97 to 100% to eradicate accessory pathways in AVRT. Complications include inadvertent AV block and recurrence of arrhythmia.[54][81]

The definition of complex fractionated atrial electrograms (CFAE) is electrograms having two fractionated deflections or a short cycle length (less than 120ms). Once ablation of CFAE is complete, proper conduction pattern can reorganize. Due to the distinct distribution of CFAE, they can are targetable by RFA.[82][83] Electrograms from healthy myocardium shows a simple morphology, but in dyssynchronous activation, they appear complex. Other authors have described CFAE proximity to areas of high dominant frequency, and CFAE also have correlations to reentry.[84] If PVI is unsuccessful electrophysiologist move to CFAE ablation.[85]

Narayan et al. reported that atrial fibrillation due to rotor activity underwent successful ablation by targeting the center of the spiral wave. This concept is called focal impulse and rotor modulation ablation (FIRM).[86] FIRM-guided RFA is used in addition to PVI ablation and atrial tachycardia/atrial flutter ablation. Reports of the long-term success of PVI are 50 to 60% in paroxysmal AF and less in persistent and permanent AF. Consistent with the findings of the CONFIRM trial Tomassoni et al. reported promising long-term success for FIRM-guided ablation for atrial fibrillation in addition to conventional ablation.[87]

The development of a surgical approach to atrial fibrillation and the pathophysiologic mechanisms behind it are closely related. In 1980 the left atrial isolation procedure was introduced. 1982 the Scheinmann catheter fulguration of the His bundle for electrical dissociation of atria and ventricles (functional total AV block) was invented: a procedure that dictates the placement of a pacemaker. Cox and other surgeons (among them Damiano, Kosakai, and Sueda) developed and improved the Maze procedure for atrial fibrillation. It has three goals: permanent ablation of AF, restoration of AV synchrony, preservation of atrial transport function. The different Cox Maze procedures try to eliminate multiple wave reentry by creating multiple lesions in both atria. Takahashi proposes to treat paroxysmal AF with PVI and persistent AF with Cox-Maze procedure although the decision should preferably be made considering individual patient factors.[88][89][13]

Differential Diagnosis

Differentiating the mechanisms arrhythmogenesis may be difficult. Micro reentry circuits, left atrial reentry spreading via Bachmann bundle to the right atrium where single spread is detected, slow conduction zone, and cul-du-ac activity of the pulmonary veins may appear as a focal activity on electrophysiologic studies. When equal PPI-TCL values are obtained for widespread points, a large macro-reentrant circuit should be suspected. Then a reentry circuit spanning left and right atrium via Bachmann bundle and Marshall ligament is possible.[90]

An important differential diagnosis for atrial fibrillation is multifocal atrial tachycardia (MAT). The correct diagnosis was made in only 22% of cases in one retrospective study. MAT is characterized by at least three different non-sinus p waves in the same lead, an atrial rate of over 100 beats per minute, and isoelectricity between p waves. Triggered activity is the pathomechanism of MAT. Since electrical cardioversion is effective only in reentrant tachycardias, cardioversion would not be helpful in this case. Treatment consists of beta-blocker, calcium channel blockade, and magnesium. This emphasizes the importance of the underlying pathomechanism for effective treatment.[91][15]

Pertinent Studies and Ongoing Trials

Reentry offers unresolved questions needing further research. Despite the high prevalence of atrial fibrillation, only insufficient treatment options are available due to missing knowledge about the true mechanism and target for therapy.[92] There is speculation about highly organized reentrant activity despite the seemingly chaotic activity in atrial fibrillation. Maybe not a single but rather a combination of mechanisms cause atrial fibrillation.[20][93] A joint workforce proposed an open classification for atrial tachycardias including focal atrial tachycardia and macro-reentrant atrial tachycardia. But the workforce also admitted that other tachycardias (atypical atrial flutter, type II atrial flutter, inappropriate sinus tachycardia) could not be well classified properly due to an incomplete understanding of the corresponding mechanism.[94]

Consultations

Insufficient treatment response and undifferentiated arrhythmias should prompt electrophysiology consultation which is a subspecialty of cardiology.

Deterrence and Patient Education

Reentry serves as a model for the pathophysiology of some self-sustaining cardiac arrhythmias and helps to diagnose and treat them.

Enhancing Healthcare Team Outcomes

Arrhythmogenesis research needs to combine computer, life sciences and clinical experts and translate new findings into evidence-based clinical care.[95] The demographic change requires broadening the knowledge about chronic and ischemic changes of the myocardium leading to arrhythmias and the importance of genetic research will increase.[96]