standardized review of atrial anatomy for cardiac electrophysiologists

21
Standardized Review of Atrial Anatomy for Cardiac Electrophysiologists Damián Sánchez-Quintana & Gonzalo Pizarro & José Ramón López-Mínguez & Siew Yen Ho & José Angel Cabrera Received: 23 October 2012 / Accepted: 22 January 2013 / Published online: 7 February 2013 # Springer Science+Business Media New York 2013 Abstract Catheter ablation of cardiac arrhythmias has rap- idly evolved from a highly experimental procedure to a standard form of therapy for various tachyarrhythmias. The advances in this field have included, first, the develop- ment of techniques of catheter ablation that often requires the precise destruction of minute amounts of arrhythmo- genic tissues and, second, techniques of resynchronization therapy that require pacing different parts of the ventricles. A detailed prepocedural knowledge of cardiac anatomy can improve the safety of the procedure and its rate success. It helps the electrophysiologist to choose the appropiate region for ablation, shortening the procedural time. The atrial anat- omy structures are usually localized before ablation by different imaging techniques such as fluoroscopy, electro- anatomic mapping, intracardiac echocardiography or multi- detector computed tomography. In this review, we describe the normal anatomy of the atria, highlighting the landmarks of interest to intervencional cardiologist, stressing their relationship to other structures. This article is part of a JCTR special issue on Cardiac Anatomy. Keywords Morphological substrate . Atrial fibrillation . Atrial flutter . Pulmonary vein . Myoarchitecture Introduction The adoption of percutaneous interventional procedures for the treatment of both structural heart defects and tachyarrhyth- mias in humans has increased the interest in cardiac anatomy. Although new diagnostic techniques are now permitting the shape of the atrial cavities to be reconstructed with exquisite accuracy, and are revealing remarkably variable arrangements of structures such as the pulmonary veins, it is helpful if the interventional cardiologist can comprehend the morphologic and architectural features of the atrial chambers as seen in the autopsied heart. In addition, a new investigational wave has emerged leading to revisitation of anatomic topics within the heart for which the information was incomplete or simply wrong. As a result, recent studies have unraveled anatomic features, architectural aspects, and histological details of cer- tain components of the heart that are of fundamental impor- tance to those seeking to understand the substrates of tachycardias and their ablation [13]. It is also necessary to understand the arrangement of the cardiomyocytes aggregated together to form the atrial walls, since this information can provide us with a better understanding of the preferential routes of conduction from one part of the atrium to the other [4]. At the same time, it is important to know how the myocardial walls of the two atrial chambers are joined togeth- er, and to recognize the location of the sinus node, the initiator of atrial activation. Our current purpose, therefore, is to review the gross morphological and structural details of the right and left atria, concentrating of features such as the terminal crest, J. of Cardiovasc. Trans. Res. (2013) 6:124144 DOI 10.1007/s12265-013-9447-2 D. Sánchez-Quintana (*) Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Extremadura, Avenida de Elvas s/n, 06071 Badajoz, Spain e-mail: [email protected] D. Sánchez-Quintana e-mail: [email protected] G. Pizarro : J. A. Cabrera Hospital Universitario Quirón-Madrid, European University of Madrid, Madrid, Spain J. R. López-Mínguez Servicio de Cardiología, Sección de Hemodinámica, Hospital Infanta Cristina, Badajoz, Spain S. Y. Ho Cardiac Morphology Unit, Royal Brompton Hospital, Imperial College, London, UK

Upload: gonzalo-pizarro

Post on 15-Dec-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

Standardized Review of Atrial Anatomy for CardiacElectrophysiologists

Damián Sánchez-Quintana & Gonzalo Pizarro &

José Ramón López-Mínguez & Siew Yen Ho &

José Angel Cabrera

Received: 23 October 2012 /Accepted: 22 January 2013 /Published online: 7 February 2013# Springer Science+Business Media New York 2013

Abstract Catheter ablation of cardiac arrhythmias has rap-idly evolved from a highly experimental procedure to astandard form of therapy for various tachyarrhythmias.The advances in this field have included, first, the develop-ment of techniques of catheter ablation that often requiresthe precise destruction of minute amounts of arrhythmo-genic tissues and, second, techniques of resynchronizationtherapy that require pacing different parts of the ventricles.A detailed prepocedural knowledge of cardiac anatomy canimprove the safety of the procedure and its rate success. Ithelps the electrophysiologist to choose the appropiate regionfor ablation, shortening the procedural time. The atrial anat-omy structures are usually localized before ablation bydifferent imaging techniques such as fluoroscopy, electro-anatomic mapping, intracardiac echocardiography or multi-detector computed tomography. In this review, we describethe normal anatomy of the atria, highlighting the landmarksof interest to intervencional cardiologist, stressing their

relationship to other structures. This article is part of a JCTRspecial issue on Cardiac Anatomy.

Keywords Morphological substrate . Atrial fibrillation .

Atrial flutter . Pulmonary vein . Myoarchitecture

Introduction

The adoption of percutaneous interventional procedures forthe treatment of both structural heart defects and tachyarrhyth-mias in humans has increased the interest in cardiac anatomy.Although new diagnostic techniques are now permitting theshape of the atrial cavities to be reconstructed with exquisiteaccuracy, and are revealing remarkably variable arrangementsof structures such as the pulmonary veins, it is helpful if theinterventional cardiologist can comprehend the morphologicand architectural features of the atrial chambers as seen in theautopsied heart. In addition, a new investigational wave hasemerged leading to revisitation of anatomic topics within theheart for which the information was incomplete or simplywrong. As a result, recent studies have unraveled anatomicfeatures, architectural aspects, and histological details of cer-tain components of the heart that are of fundamental impor-tance to those seeking to understand the substrates oftachycardias and their ablation [1–3]. It is also necessary tounderstand the arrangement of the cardiomyocytes aggregatedtogether to form the atrial walls, since this information canprovide us with a better understanding of the preferentialroutes of conduction from one part of the atrium to the other[4]. At the same time, it is important to know how themyocardial walls of the two atrial chambers are joined togeth-er, and to recognize the location of the sinus node, the initiatorof atrial activation. Our current purpose, therefore, is to reviewthe gross morphological and structural details of the right andleft atria, concentrating of features such as the terminal crest,

J. of Cardiovasc. Trans. Res. (2013) 6:124–144DOI 10.1007/s12265-013-9447-2

D. Sánchez-Quintana (*)Departamento de Anatomía y Biología Celular,Facultad de Medicina, Universidad de Extremadura,Avenida de Elvas s/n,06071 Badajoz, Spaine-mail: [email protected]

D. Sánchez-Quintanae-mail: [email protected]

G. Pizarro : J. A. CabreraHospital Universitario Quirón-Madrid,European University of Madrid, Madrid, Spain

J. R. López-MínguezServicio de Cardiología, Sección de Hemodinámica,Hospital Infanta Cristina, Badajoz, Spain

S. Y. HoCardiac Morphology Unit, Royal Brompton Hospital,Imperial College, London, UK

the cavotricuspid isthmus, Koch’s triangle and its content, theEustachian ridge and valve, the pulmonary venous orificesand their neighboring left atrial landmarks, and the architec-ture of the venoatrial junctions. We also discuss the anatom-ical features of important structures in the neighborhood of theatria and the pulmonary veins, such as the esophagus andphrenic nerves.

Location of the Atria

Both the right and left atrial chambers lie to the right of theirrespective ventricular chambers. Viewed from the front, thecavity of the right atrium is rightward and anterior, whilethat of the left atrium is mainly positioned posteriorly(Fig. 1). The plane of the atrial septum does not run in the

sagittal plane. Instead, it is orientated obliquely from ante-riorly to posteriorly rightward at an angle of around 65° tothe sagittal plane [5]. Owing to the obliquity of this septalplane and the difference between the levels of the mitral andtricuspid valvar orifices, the left atrial chamber is situatedmore posteriorly and superiorly than its right-sided counter-part. The pulmonary veins enter the posterior part of the leftatrium, with the left veins located more superiorly than theright veins. The orifices of the right pulmonary veins aredirectly adjacent to the plane of the atrial septum. Thetransverse pericardial sinus lies anterior to the left atrium,and in front of this sinus is the root of the aorta. The trachealbifurcation, the esophagus, and descending thoracic aortaare immediately behind the pericardium, being directly re-lated to the posterior wall of the left atrium (Fig. 1). Furtherbehind is the vertebral column.

Fig. 1 a This picture of an endocast from a normal heart photographedin attitudinally appropriate position, with the so-called “right heart” inblue and the “left heart” in red. As can be seen, the right atrium liesanterior to its alleged left-sided counterpart. Note the arrangement ofthe terminal crest (white broken line). b External appearance of theright and left atriums viewed from superior view. Note the location ofthe transverse sinus (yellow dotted line) and its relationship to the aorta,pulmonary trunk (PT) and atrial walls. c, d Specimens viewed from the

tilted right superior and left perspectives, respectively, to show thecourses of the esophagus (Eso) and descending aorta relative to theleft atrium. CS coronary sinus, ICV inferior caval vein, LAA left atrialappendage, LIPV left inferior pulmonary vein, LPA left pulmonaryartery, LSPV left superior pulmonary vein, OF oval fossa, RAA rightatrial appendage, RIPV right inferior pulmonary vein, RPA rightpulmonary artery, RS right superior pulmonary vein, SCV superiorcaval vein

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 125

Spatial Location of the Atrial ChambersDuring an Electrophysiological Study

Two or more fluoroscopic views are usually needed todefine the anatomic position in the heart and to estimatemore accurately the location of the exploring electrode. Thefrontal view is used to introduce and position catheters in theapex and outflow tract of the right ventricle, in the rightatrial appendage or the lateral aspect of the right atrium, andin the region of the His bundle. The left anterior oblique(LAO) projection is generally used to catheterize the coro-nary sinus independently of the type of venous approach.From an attitudinal point of view, the right anterior oblique(RAO) projection defines what is anterior, posterior, supe-rior, and inferior. The LAO defines superior, inferior, ante-rior, and posterior locations for both the right and leftatrioventricular (AV) grooves, which are almost parallel tothe plane of the image intensifier in this projection.

Components of the Atrial Chambers

Although the atria differ markedly in their shape (Figs. 1 and2), they possess the same basic components. Thus, eachatrium is made up of a venous component, an appendage,and a vestibule, with the chambers separated one from theother by the septum. These various components themselvesare supported by the bodies of the atria [6]. The body is muchmore obvious in the left than in the right atrium. The body ofthe right atrium is the part of the chamber between the site ofthe left venous valve and the septum. In the postnatal heart, itis not usually possible to recognize the site of the left venousvalve. Hence, it is difficult to distinguish the body of the rightatrium from the systemic venous sinus.

From the outside, the anterolateral portion of the rightatrium is dominated by its appendage, a roughly triangular-shaped offshoot whose apex generally points upwards, over-lapping the aortic root (Fig. 1). Its inferior margin is adjacentto the right atrioventricular groove, which contains the rightcoronary artery. When inspected from its cavity, the rightatrial appendage is large, and contains multiple pectinatemuscles (Fig. 2). The junction between the appendage andthe systemic venous sinus is marked internally by the ex-tensive and prominent terminal crest (Figs. 1 and 2), whichcorresponds externally to the terminal groove, an obviouslandmark extends vertically from the superior to the inferiorcaval vein. The smooth-walled vestibule supports the hingelines of the leaflets of the tricuspid valve, and is surroundedby the pectinate muscles of the appendage. The caval veins,along with the coronary sinus, drain into this extensivevenous component. The orifice of the superior caval veinusually has no valve, while the orifice of the inferiorcaval vein is flanked anteriorly by the Eustachian valve

(Fig. 2), an inconstant and rudimentary valve seen as acrescentic fold.

The left atrium has an obvious smooth-walled body(Figs. 1 and 2), interposed between the vestibular and pul-monary venous components, with the pulmonary veins en-tering at the four corners of the venous part, enclosing aprominent atrial dome (Fig. 1). Typically, two veins, posi-tioned superiorly and inferiorly, drain into either side of thevenous component. The endocardium of the chamber issmooth, with no muscular structure seen which is compara-ble to the right atrial terminal crest. Pectinate muscles arepresent in the left atrial appendage (Fig. 2), which arisesfrom the superolateral aspect of the body, and projectsanteriorly over the proximal left circumflex artery, runningalongside the pulmonary trunk. It is more tubular than thenormally pyramidal right appendage, and has a narrowerbase [7] (Fig. 2). The left side of the atrial septum issmooth, but may contain a central shallow area,corresponding to the oval fossa (Fig. 2). Its anatomicfeature is its two horns, which anchor it on the left sideof the anterior interatrial groove.

Structural Features of the Right Atrium

The Terminal Crest and the Area of the Sinus Node

The right atrium is the anatomic gateway to its left-sidedcounterpart, and a thorough understanding of its anatomyand anatomic variants is essential. The terminal crest marksthe division between the ridge-lined atrial appendage andthe smooth venous part [2, 8]. The crest extends from theanteromedial wall on the left side of the entrance of thesuperior caval vein (Fig. 1). It passes to the right and in frontof the venous orifice before descending laterally, curving tothe right of the entrance of the inferior caval vein, to con-tinue as an array of finer bundles that enter the region of theatrial wall well described as the inferior, or cavotricuspid,isthmus (Fig. 3). A series of muscle bundles known aspectinate muscles arise from the lateral margin of the crest.They fan out from the crest and run toward the vestibularportion (Figs. 2 and 3). The mean length of the crest wasmeasured at 51±9 mm [8] and its thickness from epicardiumto endocardium at the junction of the superior cava veinwith the posterior atrial wall was 5.5±1.3 mm [2]. One ofthe anterosuperior bundles is usually more prominent. Thisstructure continues into the tip of the appendage and it isusually described as the septum spurium (Fig. 3). It is aconvenient landmark for dividing the appendage into ante-romedial and posterolateral components. Other authors havedescribed how in some hearts, one fifth of those examined,the pectinate muscles medial to the crest end in a discreteridge, which was nominated as a second crest [9] (Fig. 2). If

126 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

present, this anatomical feature may produce difficultiesduring the ablation of the cavotricuspid isthmus.

The cardiomyocytes making up the crest are alignedmainly in longitudinal fashion along its long axis [2], thusfavoring preferential conduction (Fig. 3). By contrast, at themargins of both subepicardial and subendocardial sides ofthe crest, the cardiomyocytes are irregularly oriented, inter-mingling horizontal with oblique or longitudinal myocytes,and extending subsequently to reach the pectinate musclesor the wall of the intercaval region [2]. Other morphologicalstudies [10] suggest that small patches of replacement

fibrosis, often encountered in the crest (Fig. 3), are micro-scars of ischemic events. At all events, the crest acts as anatural barrier to conduction [11]. It may provide a substratethat is suitable for possible re-entrant mechanisms, whichcould potentially promote profibrillatory remodeling [12].

It was Keith and Flack [13], in 1907, who first describedthe location of the sinus node. The sinus node is the sourceof the cardiac impulse [13]. It can be identified at thesuperior cavoatrial junction as a spindle-shaped structurewithin the epicardial surface of the terminal groove, its tailextending toward the inferior caval vein (Fig. 3). The nodal

Fig. 2 a Opened right atrium in simulated right anterior oblique viewto show the terminal crest (TC). The crest arches anterior to the orificeof the superior caval vein (SCV) and extends to the area of the anteriorinteratrial groove, breaking up into a series of pectinate muscles whichdo not reach to the vestibule. b Four-chamber section through the heartshowing the atrial septum in profile. The floor of the oval fossa (openarrow) is the true septum. Stars mark the levels of attachments of thetricuspid and mitral valves at the septum. The inferior pyramidal space(small arrow) is covered by the vestibule of the right atrium. c Longi-tudinal section through the left atrium and left ventricle, showing thesmooth endocardial aspect of the left atrium. The black arrow indicates

the crescentic edge of the oval fossa (OF) valve. d This section takenthrough the short axis of the heart shows the thin flap valve (openarrow) and the muscular rim of the fossa (small arrows). Note thedifferent shape and size of the atrial appendages. CSO coronary sinusorifice, ICV inferior caval vein, IS interventricular septum, LAA leftatrial appendage, LCx left circumflex artery, LIPV left inferior pulmo-nary vein, LLR left lateral ridge, LSPV left superior pulmonary vein,MV mitral valve, PT pulmonary trunk, RAA right atrial appendage,RCA right coronary artery, RIPV right inferior pulmonary vein, RS rightsuperior pulmonary vein, RVOT right ventricular outflow tract, TVtricuspid valve

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 127

cells were described histologically as “striated, fusiform,with well-marked elongated nuclei, plexiform in arrange-ment, and embedded in densely packed connective tissue”[13, 14] (Fig. 3). Sections through the node also showed a

discrete area, composed of loosely packed myocytes, whichhas now been named as the paranodal area [15] (Fig. 3). Thenode itself varies in position and length along the terminalgroove. It has been observed that the tail of the node was

Fig. 3 a Opened right atrium toshow the most importantlandmarks and its fourcomponents. Note the OF andthe TC which is a thick C-shaped muscular trabecula thatdistally ramifies to form thepectinate muscles. bEndocardial aspect of the rightatrium. The “septum spurium”(SS) is the most prominentanterior pectinate musclearising from the terminal crest.c Scanning electron micrographof nonmacerated cross sectionthrough the body of theterminal crest shows mainlylongitudinal myocytes (openarrow) with interminglingoblique or lateral (stars)myocytes. Bar 35 μm. dScanning electron micrographof nonmacerated cross-sectionof the body of the terminal crestwhich are encased in dense andcoarse connective tissue matrix(stars) in a specimen from a75 year old. Bar 90 μm. eHistological section of the sinusnode (black dotted linedelineates the nodalboundaries) within a densematrix of connective tissue(green) and showing nodalextensions to superior cavalvein (SCV) and epicardium. fHistological section of thenodal body (van Gieson’sstain). Note the irregularcontour of the node towards theneighboring myocardium(arrows). CSO coronary sinusorifice, ICV inferior caval vein,RAA right atrial appendage, TVtricuspid valve

128 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

located nearer to the endocardial surface of the crest than thehead or body of the node in just over one quarter of speci-mens [16]. With age, the amount of connective tissueincreases with respect to the area occupied by the nodalcells [17]. At the periphery of the node, the histologicallyspecialized cardiomyocytes are mixed with those of theworking myocardium (Fig. 3). In addition, multiple radia-tions or extensions interdigitating with the working atrialmyocardium have been described. These penetrate intra-myocardially into the crest, and toward the epicardium andthe myocardium of the superior caval vein [16]. Sleeve-likeextensions of right atrial myocardium that connect to theright atrium are usually found at the proximal level of thecaval venous orifice (Fig. 3). Thus, atrial excitation from thenode can propagate directly into the musculature of thesuperior caval vein. These cardiomyocytes were found tohave pacemaker activity, with the enhanced automaticitysuggested to play a role in the arrhythmogenic activity ofthe superior caval vein, potentially establishing ectopic trig-gers that could initiate paroxysmal atrial fibrillation [18]Table 1.

Koch’s Triangle, the Anatomic Locationof the Atrioventricular Node

Another area of the right atrium of significance to interven-tional cardiologists is the triangle of Koch. This triangle isbordered posteriorly by a fibrous extension from the Eusta-chian valve called the tendon of Todaro [19] (Fig. 4). Theanterior border is demarcated by the attachment of the septalleaflet of the tricuspid valve. The apex of this trianglecorresponds to the central fibrous body of the heart and isthe site of penetration of the bundle of His. The so-calledfast pathway of atrioventricular nodal reentry tachycardia,the most common type of reentrant supraventricular tachy-cardia, corresponds to the area of musculature close to theapex of the triangle of Koch (Fig. 1d). The base of thetriangle is the orifice of the coronary sinus and the vestibule

of the atrium immediately anterior to it (Fig. 4). This part ofthe vestibule, confined between the orifice of the coronarysinus and the attachment of the septal leaflet of the tricuspidvalve, is the septal isthmus. It is often the target area forablation of the slow pathway into the atrioventricular node[20] (Fig. 5a). It is also the target for ablation of isthmus-dependent atrial flutter. The dimensions of Koch’s trianglevary from one individual to another. This is clinically rele-vant in the case of catheter ablation procedures, which arelargely guided by anatomic landmarks. In the 45° RAOprojection, the plane of the triangle of Koch is parallel tothat of the image intensifier. To establish whether the cath-eter is on the triangle of Koch, the RAO and LAO viewsmust be combined. The LAO projection differentiates para-septal locations from inferior, anteroinferior, and anteriorpositions of the probing electrode. The region of the Hisbundle is superior, whereas the orifice of the coronary sinusis inferior. Right atrial angiography in the RAO projectionnot only displays the limits and variable dimensions of thetriangle of Koch but also identifies the exact position of thecatheter used for ablation in relation to the anterosuperiorand posteroinferior limits of the tricuspid valve. This appliesto ablative procedures in patients with AV nodal reentrytachycardia; in patients with inferior paraseptal, septal, andsuperior paraseptal accessory pathways; and in patients withcertain forms of atrial tachycardia arising from the triangleof Koch. The dimensions of the triangle of Koch may warnthe interventional electrophysiologist about the potentialdangers of inducing unwanted damage over the atrioventric-ular node (Fig. 5b).

The atrioventricular node itself is found at the apex ofKoch’s triangle. It consists of a compact portion and areas oftransitional cardiomyocytes [21]. The compact portion liesover the atrial surface of the central fibrous body (Fig. 4). Itpossesses rightward and leftward inferior extensions, withthe right extension running close to the tricuspid annulus[22] (Fig. 4). The node was found to be displaced toward thebase of the triangle in three quarters of specimens with

Table 1 Points of interest forablation of tachycardias whoseanatomical substrate were locat-ed in the region of the sinusnode, Koch’s triangle, and cav-otricuspid isthmus

1°—The sinus node varies in position and length along the terminal crest

2°—Thickness of the terminal crest

3°—Atrial myocardial extensions into superior caval vein

4°—Risk of right phrenic nerve injury

5°—The dimensions of Koch’s triangle vary from one individual to another

6°—The atrioventricular node is found generally at the apex of Koch’s triangle

7°—Close anatomic proximity of AV nodal artery to endocardial surface at the base of Koch’s triangle

8°—His bundle surrounded and isolated by connective tissue which confers a better protection againstablation energy

9°—Length of the cavotricuspid isthmus: shorter ‘central isthmus’

10°—A large Eustachian ridge/valve may lead to longer and more difficult ablative sessions

11°—The presence of a large sub-Thebesian recess is associated with a difficult ablation

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 129

Ebstein’s malformation, in which the inferior extensionsreached the level of the cavotricuspid isthmus [23]. Thetransitional cardiomyocytes are intermediate in size betweenthose of the compact node and the atrial working cardio-myocytes. They are surrounded by a greater quantity ofconnective tissue matrix than that covering the workingmyocytes, but they are not insulated from the adjacentmyocardium. Instead, they form a kind of bridge betweenthe working and nodal myocardium and collect electricalinformation from the atrial walls, transmitting it to thecompact node, which continues distally as the His bundle.This penetrating part of the atrioventricular conduction axiscan readily be distinguished from the compact node at thepoint where the axis itself becomes completely surroundedby the insulating tissues of the central fibrous body (Fig. 4).The bundle, of course, is the only pathway for electrical

conduction to the ventricles [21]. The artery supplying thenode originates from the apex of the U turn of the distal rightcoronary artery, and penetrates into the base of the inferiorpyramidal space at the level of crux of the heart in aroundnine tenths of patients [24] (Fig. 4). In the remaining onetenth of patients, it originates from the terminal portion ofthe circumflex artery or, uncommonly, is a dual structure,arising from both the right and circumflex arteries. Theartery provides branches to the inferior pyramidal space,interatrial septum, compact node, and penetrating bundleof His. In our postmortem study, we found that the meandistance of the artery to the endocardial surface at the baseof Koch’s triangle was 3.5±1.5 mm [24] (Fig. 4). This mayexplain the possible risk of coagulating the artery duringradiofrequency ablation in the region of the slow pathway.Complete atrioventricular block, when encountered, is

Fig. 4 a, b Transillumination.Endocardial views of the rightatrium to show the landmarksof the triangle of Koch. Thevestibule of the right atrium andthe coronary sinus orifice(CSO) form the lower limit. Theapex of the triangle is themembranous septum. c Basalview showing macroscopicallythe course of the AV nodalartery across the inferiorpyramidal space. At the base ofthe triangle, the artery runsinferior to the mouth of thecoronary sinus and follows acourse close to the septalattachment of the tricuspidvalve (TV). d–f Sagittalsections stained with elastic vanGieson through the inferiorextensions of the AV node (d),compact part of the AV node(black dotted line delineates thenodal boundaries) in e, andpenetrating bundle of His (f)embedded in fibrous tissue. gSagittal section through themouth of the coronary sinus(CS) showing the proximity ofthe artery to the endocardium atthe base of the triangle of Koch.ICV inferior caval vein, MVmitral valve, RAA right atrialappendage, SCV superior cavalvein, STR sub-Thebesianrecess, TC terminal crest, TTtendon of Todaro

130 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

commonly a direct result of tissue injury to the compactnode itself after ablation of the fast pathway [25] (Table 1).

The Inferior or Cavotricuspid, Isthmus, and Atrial Flutter

The commonest type of atrial flutter is the so-called isthmus-dependent variant, in which the reentrant circuit is confined tothe tricuspid vestibule, with the wave-front progressing in acounterclockwise direction across the area between the orificeof the inferior caval vein and the tricuspid valve (Fig. 6). Thisarea, the cavotricuspid isthmus, is the target of catheter-directed ablation procedures, which are the treatment of choicefor cure of atrial flutter [26]. Autopsies, angiographic, andechocardiographic studies have all shown that the anatomy ofthis structure is highly variable [27, 28]. Patients with short andstraight isthmuses require fewer ablation procedures andshorter exposure to radiation. Obstacles, such as a large Eusta-chian ridge or valve, or a deep sub-Thebesian recess, may also

lead to longer and more difficult ablative sessions [29](Figs. 5c and 6). We have divided the isthmus into threeparallel levels [28]. With the heart in attitudinal orientation,we identified and measured its length at three different levels,namely paraseptal at 24±4 mm, inferior at 19±4 mm, andinferolateral at 30±3 mm (Fig. 6). The paraseptal isthmusforms the base of Koch’s triangle. The inferior isthmus, alsoknown as the central isthmus owing to its location between theother two components, represents the optimal target for abla-tion, since this is the site where the orifice of the inferior cavalvein is closest to the insertion of the septal leaflet of thetricuspid valve (Fig. 6). It is also shown that most diametersare larger in patients with flutter when compared to controlgroup [30]. The enlarged right atrium including the cavotricus-pid isthmus may provide the pathophysiologic basis to sustainatrial flutter within an otherwise universally existing anatomicsubstrate. Fluoroscopically, these three levels of the isthmuscannot be visualized without angiographic techniques. In the

Fig. 5 a This is a human heart, note that the AV node and bundle ofHis (overlay in yellow) are located within the triangle of Koch. Abla-tion in this area is avoided in order to prevent heart block. An injuryfrom radiofrequency catheter ablation, however, is present in the baseof the Koch’s triangle (dotted line). Ablation of the base of the triangleor paraseptal isthmus is commonly the target for ablation of the slowpathway in AV nodal reentrant tachycardia. b Cryolesions histologicalcharacteristics at the AV node level in a pig heart 1 week after a singlecryoenergy application. Note shape of the lesion resembling a prolatehemisphere (dotted yellow line) and the homogeneous nature of cry-olesion, with a smooth and sharp demarcation from intact myocardium,

with replacement of muscle by granulation tissue at perimeter of thelesion and coagulative necrosis (asterisks) of underlying myocardium.Radiofrequency histological sections (Masson’s trichrome stain) in apig heart 1 day after application at the level of c central isthmus and dright inferior pulmonary vein. Note in c the subepicardial and endo-cardial bleedings and the disruption of the endocardium at sub-Thebe-sian recess (asterisk). Note in d the shape of the lesion (dotted blueline) with coagulative necrosis of underlying myocardium and subepi-cardial bleeding. STV septal tricuspid valve, CSO coronary sinus ori-fice, FO fossa oval, CFB central fibrous body, IVS interventricularseptum ventricular septum

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 131

LAO projection, three areas must also be distinguished: aparaseptal level (5 o’clock position), a central area (6 o’clockposition), and an inferolateral level (7 o’clock position). Thecardiac multidetector computed tomography (MDCT) can beadvantageous for noninvasively characterizing the cavotricus-pid isthmus, including its size, depth, and anatomic relation-ship with the inferior caval vein, Eustachian ridge, andcoronary sinus ostium. In addition, cardiac MDCT may alsodepict deep pouch-like recesses, which are commonly presentalong the cavotricuspid isthmus, which can make the creationof a complete ablation line to block the arrhythmia difficult.

The Eustachian Ridge or Valve

The Eustachian ridge is a rim between the oval foramen andthe coronary sinus that is in continuation with the insertionof the Eustachian valve. The free border of the Eustachianvalve continues in a subendocardial level as the tendon of

Todaro, which runs in the musculature of the ridge (Fig. 6).The Eustachian valve can be fluoroscopically visualized inthe right anterior oblique projection only after injection ofcontrast material into the inferior caval vein, close to theright atrial junction. The Eustachian valve/ridge may belarge and muscular in some cases, posing an obstacle tocatheter passage. A large ridge is an anatomic barrier, andforms a line of fixed conduction block during typical flutter.It has been demonstrated that in patients with large ridges,block of the paraseptal isthmus can be obtained only aftercomplete ablation of the enlarged ridge [31]. Cabrera et al.[28] observed that, in one quarter of their specimens, theridge was thickened, with a mean thickness of 3.2±0.8 mm,and a range from 2.1 to 4.3 mm. A ridge thicker than 4 mmis also seen in one quarter of the normal population studiedwith computed tomography [32]. The angiographic studycarried out by Heidbüchel et al. [27] similarly revealed anenlarged ridge in one quarter of patients, with a consequent

Fig. 6 a Opened right atrium in simulated right anterior oblique viewshowing the position of the ablation catheter at the site (central isthmus)of application of radiofrequency. b, c Transillumination. The endocardialsurface of the right atrial isthmus is displayed to show the three levels(inferolateral, central or inferior, and paraseptal). Note the pouch (sub-Thebesian recess or STR) at the central isthmus and the distal branchingof the terminal crest (TC) that feed into the inferolateral isthmus. d Shortaxis through the interatrial septum (green arrow). Note by transillumina-tion the oval fossa (OF), the membranous septum and the so-called left

lateral ridge (LLR) between the left atrial appendage (LAA) and the leftPVs. e, f Histological sections (Masson’s trichrome stain) at the level ofthe central (e) and paraseptal (f) isthmus illustrating its different myocar-dial thickness. g Transillumination of the right atrial isthmus. Note thelarge sub-Thebesian recess (STR) in this specimen. CSO coronary sinusorifice, ICV inferior caval vein, LI left inferior pulmonary vein, LS leftsuperior pulmonary vein, PT pulmonary trunk, RAA right atrial append-age, RVOT right ventricular outflow tract, SC supraventricular crest, SCVsuperior caval vein, TV tricuspid valve

132 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

increase in the number of pulse applications required for theachievement of successful block (Table 1).

The Sub-Thebesian Recess or Sub-Thebesian Sinus

This recess is an extension of the pouch-like isthmus foundunder the orifice of the coronary sinus (Fig. 6), never beingfound in the lateral third of the cavotricuspid isthmus. It isoften described as being sub-Eustachian, since when the heartis positioned on its apex, the recess lies directly beneath thefibrous flap that in many hearts is found adjacent to the orificeof the inferior caval vein. When viewed in attitudinally appro-priate position, the recess is seen to be beneath the Thebesianvalve, which is the remnant of the valve of the embryonicvenous sinus adjacent to the mouth of the coronary sinus(Fig. 6). In autopsied specimens, this recess was found inone sixth of the adult hearts [9]. The recess, on average, was9.3±3.7 mm long and 6.1±1.9 mm deep. In the majority ofspecimens, the recess was membranous with scarce muscularfibers [28]. In one angiographic study, this recess was ob-served in almost half of the patients and had a mean depth of4.3±2.1 mm [27]. The dimensions vary from one individual toanother, which is clinically relevant in the case of catheterablation procedures in this area. The presence of a large recess,or deep pouches, is associated with significantly more appli-cations of current as compared to those having a straightisthmus [28] (Table 1). Local delivery of current may beimpaired by this structure because an area of limited bloodflow results in delayed cooling of the catheter tip.

The Atrial Septum

Partitioning the atrial chambers, the true atrial septum islimited to the floor of the oval fossa and its immediatemuscular rim at the anteroinferior part, this latter componentbeing confluent with the apical part of Koch’s triangle(Figs. 3 and 4). The entirety of the superior and posteriorrims of the fossa, along with much of the anterior rim, is nomore than infoldings of the atrial walls (interatrial grove).The true septum is the flap valve, along with its point ofanchorage antero-inferiorly. As indicated, this antero-inferior rim becomes confluent with the floor of the triangleof Koch, but much of the triangle is a sandwich rather than aseptum, since the atrial wall overlaps the crest of the ven-tricular septum in this area, with an upward extension of theinferior atrioventricular groove separating the atrial from theventricular muscle masses. Although often described as theposterior septum, in reality this is the inferior pyramidalspace (Fig. 4). A transseptal approach is used if access tothe left side of the heart is mandated. In some cases, percu-taneous puncture of the interatrial septum for the left heartcatheterization can be difficult and may result in life-

threatening complications, particularly in patients with atyp-ical anatomy or a small oval fossa. Given that a majorportion of the atrial septation is formed by infolding rightand left atrial walls (interatrial groove), puncture outside thelimited margins of the oval fossa during transseptal inter-ventions will perforate the heart. Fluoroscopic angulationsused for transseptal punctures must be individualized be-cause of the variability in the position of the heart in thethorax. Experienced operators may perform very efficientlythe puncture of the oval fossa in the posteroanterior projec-tion; others may prefer a very angulated LAO projection(>45°). In the RAO projection, the oval fossa is posteriorand superior or at the same level as the site of recording ofthe His bundle potential. By means of cardiac MDCT,technologies may be useful in planning transseptal interven-tions by identifying the anatomy of the interatrial septumand demonstrating the precise morphology of a possiblepatent foramen oval, as well as identifying the presence ofan atrial septal defect, or also a lipomatous hypertrophy ofthe interatrial septum, which is characterized by accumula-tion and deposition of fat in the interatrial septum and canresult in constriction of the fossa oval (Table 2).

Structural Features of the Left Atrium

The Left Atrial Wall and its Thickness

The wall of the left atrium measures, on average, 3 mm inthickness. It is thicker than the walls of the right atriumwhen we exclude considerations of the terminal crest. Al-though the left atrium has relatively smooth walls (Figs. 2,3, 4, 5, 6, and 7), it is by no means uniform in thickness or inmyoarchitecture. The walls can be described as being ante-rior, superior, left lateral, septal, and posterior. The anteriorwall is located behind the ascending aorta and the transversepericardial sinus (Fig. 7). From epicardium to endocardium,its width is 3.3±1.2 mm, with a range from 1.5 to 4.8 mm inunselected postmortem hearts. This wall, nonetheless, canbecome very thin at the area near the vestibule of the mitralannulus (Fig. 7), where it measures an average of 2 mm inthickness. The roof, or superior wall, is in close proximity tothe right pulmonary artery. Its width ranges from 3.5 to6.5 mm, with a mean thickness of 4.5±0.6 mm. The thick-ness of the lateral wall ranges between 2.5 and 4.9 mm, witha mean of 3.9±0.7 mm [1]. The measurement of the meanthickness of the atrial septum in normal hearts at the level ofthe anteroinferior portion of the muscular rim is 5.5±2.3 mm, and the mean thickness of the flap valve is 1.5±0.6 mm [1]. These results agree with previously publishedstudies performed by transesophageal echocardiography[33]. The posterior wall is non-uniform [34] (Fig. 7), andis a target of currently used ablative procedures in patients

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 133

with atrial fibrillation. Its thickness is greatest inferiorly, at6.5±2.5 mm, when measured immediately superior to thecoronary sinus and between 6 and 15 mm from the mitral

annulus. By contrast, it is thinnest, at 2.2±0.3 mm, with arange from 1.2 to 4.5 mm, at the level of the right or leftvenoatrial junctions [35] (Table 2).

Table 2 Points of interest for ablation of tachycardias whose anatomical substrate were located in the left atrium and coronary sinus

1°—Puncture outside the limited margins of the oval fossa during transseptal interventions will perforate the heart

2°—Cardiac CT technologies may be useful in planning transseptal interventions (patent foramen oval, atrial septal defect, lipomatous hypertrophy)

3°—Non-uniform myocardial thickness of the left atrial wall

4°—Marked variability in pulmonary veins anatomy

5°—Thickness non-uniform of the myocardial sleeves of the pulmonary veins

6°—Autonomic nervous system on the epicardial surfaces of both the right and left superior veins

7°—Endocardial ridge: the left lateral ridge between the entrance of the left pulmonary veins and the mouth of the left atrial appendage

8°—Variability in the morphology of the left atrial appendage orifice

9°—Extra-appendicular pectinate muscles (mitral isthmus and vestibule)

10°—Marked variability in the dimensions of the mitral isthmus and its relationships (coronary sinus and circumflex artery)

11°—Changes in the musculature of Bachmann’s bundle and arrhythmias

12°—The coronary sinus is an important channel for mapping and for reaching accessory atrioventricular pathways around the mitral valve

13°—The coronary sinus is used as a conduit for left ventricular pacing during cardiac resynchronizarion therapy

14°—Close proximity of the left atrium to the esophagus, vagus nerve and left phrenic nerve

Fig. 7 a, b Longitudinal sections of two hearts illustrating endings ofthe pulmonary veins into the left atrium. In a, the specimen showing ashort vestibule or funnel-like common vein for both left PVs. Note in bthat an individualized ending of the left superior PV (LS) and the leftinferior PV (LI) into the left atrium. The left PVs lie superior andposterior to the mouth of the LAA, both separated by a muscular foldso-called LLR. The anterior wall behind the ascending aorta can be-come very thin at the area near the vestibule of the mitral valve(asterisk). The line connecting the inferior margin of the ostium ofthe left inferior PV to the mitral annulus is the so-called the left atrial

isthmus (blue dotted line). c, d Two heart specimens sectioned tran-versally with the roof of the left atrium removed and viewed fromabove to shows the entrance of the pulmonary veins. Note that in c, thearrangement of four individualized ending of the PVs into the leftatrium. In d, there are four PVs. However, the left PVs show avestibule or funnel-like common vein before opening into the leftatrium (blue arrow). CS coronary sinus, LAA left atrial appendage, LIleft inferior pulmonary vein, LLR left lateral ridge, LS left superiorpulmonary vein, MV mitral valve, RI right inferior pulmonary vein, RSright superior pulmonary vein

134 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

Pulmonary Veins

In recent times, various non-invasive imaging techniques,such as magnetic resonance imaging and multidetector com-puted tomography, have shown marked variability in pulmo-nary venous anatomy. This is well demonstrated in the numberof venous orifices, with some patients having five distinctopenings, while others have common trunks. A commonunilateral orifice is seen in one quarter of patients [36, 37],beingmore frequent on the left than on the right. The existenceof extra veins, most commonly with a separate right veindraining the middle lobe of the right lung, is another commonfinding [38], and is also present in up to one quarter of patients[39]. Our anatomical study on a series of 35 heart specimensfound the classic arrangement of four orifices in three quarters,with three tenths of these in the setting of a short vestibule orfunnel-like common vein (Fig. 7). We found five venousorifices in 17 %, while the remaining 9 % had a common veinon the left or right side [40]. As well established by the groupof Haïssaguerre [41], the left atrium is electrically connectedto the veins by muscular sleeves. Four fifths of the focal

triggers for atrial fibrillation are located in this pulmonaryvenous myocardium.

Morphological Studies [42]

It was the early work by Nathan and Eliakim that establishedthe presence of the muscular sleeves, revealing a mean extentof 13mm and a maximal extent of 25mm. These sleeves wereshown to be better developed in the upper than in the lowerveins. Histological studies [1, 43] showed that the venouswalls were composed of a thin endothelium, a media ofsmooth muscle, and a thick outer fibrous adventitia (Fig. 8).The transition from atrial to venous walls was gradual as themyocardial sleeves of ordinary atrial myocardium from theleft atrium overlapped with the smooth muscle of the venouswall. Themyocardial sleeves lay external to the venousmedia,and internal to the epicardium and adventitia. They werethickest at the venoatrial junction, with a mean of 1.1 mm,and thinned out distally. Their thickness was far from uniform,with the inferior walls of the superior veins, and the superiorwalls of the inferior veins, having the thicker sleeves (Fig. 8).

Fig. 8 a Longitudinalhistological section in Masson’strichrome stain shows the thickeratrial wall becoming thinner atthe entrances of the left PVs toform the muscular sleeves, whichtaper toward the lungs. b Cross-histological sections (Masson’strichrome stain) through the leftPVs showing variations incircumferential thickness of themyocardial sleeves (arrows). cMuscle bridges (arrows) betweenthe superior and inferiorpulmonary veins connectobliquely superior inferiorly. d, eCross-histological sectionsillustrating in d the presence ofgaps of connective tissue bridgesbetween the myocardial fibers(red arrows) and note in e a smallarea of myocardial degenerationwith fibrous replacement(arrows). f Transillumination ofthe roof and posterior view of theleft atrium of a 58-year-old manshowing the acetylcholinesterase-stained epicardial ganglionatednerves (red arrows) extending tothe superior surface of the leftveno-atrial junctions. LI leftinferior pulmonary vein, LS leftsuperior pulmonary vein, RI rightinferior pulmonary vein, RS rightsuperior pulmonary vein

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 135

In particular, we were able to show two structural features inspecimens without heart disease. First, throughout the vein,and even at the venoatrial junction, there were gaps in themyocardial sleeves that were mainly composed of fibroustissue [43]. These gaps create discontinuities between groupsof myocytes (Fig. 8). Second, interpulmonary myocardialconnections are common, occurring in 15 of the 18 heartsexamined (Fig. 8) [44]. Bridges of atrial myocardium, andcrossing strands, have been observed connecting superior andinferior veins, occurring more frequently between the leftveins than the right veins. They are located in the subendocar-dium in just over half, in the subepicardium in just over onequarter, and in both aspects in one fifth [44]. The arrangementof the bundles of cardiomyocytes within the sleeves is rathercomplex. In contrast to previous reports [42], our findingsrevealed a mesh-like arrangement of muscular fascicles, madeup of circular-orientated bundles that interconnected withbundles that ran in a longitudinal orientation [43]. We havesuggested that such an arrangement leads to anisotropic con-duction between the bundles, which can act in itself as a focaltrigger, or provide the substrate for micro re-entry. Patchyareas of fibrosis (Fig. 8), which were also detected, may takean active part in the role of the pulmonary venous muscularsleeves in initiating atrial fibrillation [43]. Interestingly, nocorrelation was seen between the age of the patients and thehistological findings. Another important anatomical feature isthat these myocardial connections may be the anatomicalsubstrate for electrical links between different pulmonaryveins. This may have clinical implications for local discon-nection of the veins when attempting radiofrequency catheterablation [44]. Other studies have suggested that the triggersand drivers for fibrillation to be found in the muscular sleeves,and in the posterior left atrial wall, are at least partially modu-lated by the autonomic nervous system [45]. Vaitkevicius et al.[46] carefully examined the morphologic pattern of nervesand ganglia supplying the human pulmonary veins. Theyobserved the richest areas containing epicardial ganglia, fromwhich intrinsic nerves extend to the veins, concentrated at theinferior and superior surfaces of both the right and left superiorveins (Fig. 8). No ganglia were identified beneath the venousendothelium. These locations, therefore, might be consideredas potential targets for focal ablation in patients with atrialfibrillation (Table 2).

The incidence of pulmonary vein stenosis caused by atrialfibrillation ablation was reported as 3–42 %, but had de-creased to <1 % due to improved techniques. These improve-ments include changing the ablation site from inside thepulmonary veins to outside the orifice of the pulmonary veins,reducing the target temperature and amount of radiofrequencyenergy delivery, and using a 3D mapping system to guide thecatheter [47]. Symptoms such as cough, chest pain, dyspnea,hemoptysis, or recurrent lung infection, are more likely seenwith severe stenosis (>70 %). However, even severe

pulmonary vein stenosis or complete pulmonary vein occlu-sion may be symptomatic. Patients with symptomatic andsevere pulmonary vein stenosis will require therapeutic pro-cedures, such as stenting and balloon angioplasty. Thus,follow-up imaging postablation (Fig. 5d) is crucial for theearly detection and prompt treatment of PV stenosis.

The Left Lateral Ridge

The left atrium does not have a terminal crest, but it has a so-called ridge, which was already described in 1907 by Keith[47] as the left tænia terminalis [48] or terminal band or strip,and later by Papez [48] as the left posterior crest [49]. This leftlateral ridge interposes between the entrance of the left pulmo-nary veins and the mouth of the left atrial appendage (Fig. 9).This is no more than an infolding of the atrial wall. It is,nonetheless, the most relevant structural prominence to be seenin the endocardial surface of the left atrium (Fig. 9). The shapeand size of this ridge is of relevance during attempted catheterablation of atrial fibrillation, when the operator encircles theorifices of the left pulmonary veins, or attempts to ablateextrapulmonary venous triggers arising around or inside theappendage. A three-dimensional study based on resonanceimaging showed that the ridge was pointed in shape, andnarrower than 5 mm in the majority of patients, thus determin-ing the possibility of obtaining stable positions for the catheterin this region [50]. Our anatomical study showed that the ridgeis a fold of the atrial wall, having a mean width that is narrowersuperiorly than inferiorly, and possessing thicker myocardiumat the anterosuperior level than postero-inferiorly [3]. The veinor ligament of Marshall is located at the epicardial aspect of theridge (Fig. 9), in close proximity to the endocardial surface, at adistance of 3 mm at the superior level of the ridge in almostthree quarters of the specimens [3]. The oblique vein of Mar-shall, a remnant of the left superior caval vein, descends alongthe lateral and posterior walls of the left atrium, extendingbetween the appendage and the left pulmonary veins (Fig. 9).It is present in around nine tenths of the population [51]. It joinsthe cardiac venous system at the junction of the great cardiacvein and the coronary sinus, approximately 3 cm away from theright atrial opening of the sinus (Fig. 9) [51]. The vein is short,no more than 2–3 cm in length, and its superior part can beobliterated by fibrosis. Complete fibrosis or obliteration in theform of a cord or ligament is seen in up to one eighth of cases[52]. The average diameter is 1 mm, and the angle made withthe sinus varies between 25° and 50° [53]. In clinical studies,electrical activity originating from the vein or ligament can berecorded from the endocardial aspect of the left atrium, in oraround the orifices of the left pulmonary veins [54]. Postmor-tem human studies demonstratedmultiple connections bymyo-cytic bundles that crossed the oblique vein of Marshall toconnect with different structures, such as the left lateral ridge,the free wall of the left atrium, the muscular sleeve of the

136 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

coronary sinus, and the atrial junctions of the left pulmonaryveins [3]. Additionally, abundant ganglia and fibers of theautonomic nervous system are present in the environs of thevein or ligament of Marshall, and its adjacent epicardium,contains, with a higher neural density also observed that theepicardial aspect of the ridge, particularly at its superior levelwhere it is relation with the opening of the left superior pulmo-nary vein [3]. Other authors have raised the possibility that theintrinsic cardiac nerves, notably the superior left ganglionatedplexus, can activate and contribute to atrial fibrillation [55].

The Left Atrial Appendage

In human hearts, the left appendage is characteristically a smallfinger-like extension of the atrium, with a multilobulated ap-pearance in four fifths of hearts [56] (Fig. 10). The tip of theappendage can be in a variety of positions, lying over thepulmonary trunk, or left anterior descending coronary artery

(Fig. 4), or pointing posteriorly, or even toward the back of theaorta (Fig. 10). The circumflex artery runs epicardially in thefat-filled atrioventricular groove, related to the smooth anteriorvestibule and in close proximity to the inferior border of theorifice of the appendage (Fig. 10). The shortest distance fromthe mouth of the appendage to the circumflex artery was lessthan 5 mm in four fifths of our unselected human postmortemhearts. In computed tomographic studies, the artery was foundwithin 2 mm of themouth of the appendage in three quarters ofcases, an anatomic detail to be considered when ablating insideor around its mouth [57]. The appendage has crenellations, orlobes, that are potential sites for deposition of thrombus, butare challenging to image adequately [56]. Most intracardiacthrombus originates in the left atrial appendage during andafter atrial fibrillation causing stroke, infarction, and emboli.Despite the advances in treatments with the new oral anti-coagulants, approximately one third of patients are consideredat high risk of bleeding. Therefore, the interventional treatment

Fig. 9 a Endocardial visualization of the left posterolateral wall.Note the prominent left LLR between the LAA and both LS and LIpulmonary veins. In this specimen, extrapectinate muscle trabecu-lations extending inferiorly from the appendage to the vestibule ofthe mitral valve (MV; arrows). b Dissection to show the myocytearrangement in the subepicardium of the left lateral ridge. Notethe multiple myocyte connections (asterisks) between the vein ofMarshall (VOM) with the lateral ridge and the coronary sinus (CS)

muscle sleeve. c, d Macroscopical and histological section (Mas-son’s trichrome stain) of a specimen showing a pointed profile ofthe endocardial left lateral ridge extending to the inferior marginof the LS pulmonary vein. The vestibule overlies the LCx andGCV. e This histological section in similar orientation shows aflattened profile of the fold that forms the ridge. There is a smallartery (arrow) in the fold. RIPV right inferior pulmonary vein, RSright superior pulmonary vein

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 137

for left atrial appendage closure represents a complementaryand effective treatment for this group of patients. Given thevariability of the left atrial appendage orifice morphology, adetailed knowledge of its anatomical characteristics could bevery useful when planning the intervention. Owing to tubularshape of the left atrial appendage, the junction with the atriumis narrow, often defined as a waist. On the endocardial aspect,the superior and posterior borders of the orifice of the append-age are well demarcated by the ridge separating the mouthfrom the orifices of the left superior pulmonary veins (Figs. 7,8, and 9) Lacking a ridge, the anterior and inferior borders are

less well-defined. The orifice of the appendage is not round,being oval in shape, with a mean long diameter of 17.4±4 mmand short diameter of 10.9±4.2 mm [7]. While the rim of theorifice is smooth, a complicated whorl-like network of pecti-nate muscles lines the endocardial surface of the appendage[58] (Figs. 9 and 10). In between the muscle bundles, the wallis paper thin. In just over a quarter of specimens, musculartrabeculations can be found extending inferiorly from theappendage to the vestibule of the mitral valve (Fig. 9). Theseextra-appendicular myocardial bands correspond to the smallposterior set of pectinate muscles originating from the

Fig. 10 a Internal view of the LAA showing the long and short diam-eters of the ostium of the appendage (double arrows). Note the extrap-ectinate muscle trabeculations (arrow). b–e Images demonstratingsignificant interindividual variation in left atrial appendage morphology.Note in d that the tip of the LAA oriented inferiorly and in e the tip isoriented superiorly and located between PT and the left atrial body (redarrow). f, g Silicone casts that show the morphological appearance of theLAA, which may be classified into two types: slender like a crooked

finger (f) and stump-like (g). h Histological section (Masson’s trichromestain) showed the internal structure of the LAA and its close proximity toadjacent structures. Note the thin wall of the appendage in between thepectinate muscles. i In this specimen, the epicardium has been removed toshow the arrangement of the LCx painted in red. Note the relationshipbetween the LAA and the artery. CS coronary sinus, LCA left coronaryartery, LI left inferior pulmonary vein, LV left ventricle, LS left superiorpulmonary vein, MV mitral valve, VOM vein of Marshall

138 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

myocardial bundles to embrace the appendage [3]. In thosehearts with extra-appendicular posterior pectinate muscles, theareas in between the muscular trabeculae and the atrial wallbecome exceptionally thin, no more than 0.5 mm, increasingthe risk of cardiac perforation during ablative procedure [3](Table 2).

The Left Atrial Isthmus or Mitral Isthmus

Although the posteroinferior area of the lateral wall betweenthe orifice of the left inferior pulmonary vein and the mitralannulus (Fig. 11) cannot be considered an anatomic entity, it isnow termed by electrophysiologists as the left atrial isthmus,or mitral, isthmus. Linear ablations connecting the inferiormargin of the ostium of the left inferior pulmonary vein andthe mitral annulus, particularly when complete linear block isachieved, appear to increase the success rate of catheter abla-tion in patients with atrial fibrillation, and prevent macro-reentry around the mitral annulus or the left veins [59]. Thecreation of such lesions by catheter ablation, nonetheless, maybe associated with significant complications.

The isthmus showed a marked variability in its dimensions,with considerable differences in thickness of the myocardiumat various levels and among different hearts [60]. The meandistance between the left inferior vein and the mitral annulusranged between 17 and 51 mm, with a mean of 34.6 mm. Thewall thickness midway between the veins and the mitralannulus was 2.8 mm, with a range from 1.2 to 4.4 mm. Incontrast, a more recent histological examination revealed that

the thickest atrial wall was midway between the mitral annu-lus and the left inferior vein, with tapering at either end of theisthmus [61]. On the other hand, Wittkampf et al. [61] havesuggested that the muscular sleeve around the coronary sinus,and the close anatomic proximity with the circumflex artery,are the two major anatomic determinants for the creation ofconduction block across the isthmus (Fig. 11). The coronarysinus is always a close neighbor of the circumflex artery,which crosses the venous structure in the majority of speci-mens. The local cooling mediated by atrial arteries and veinsmay protect the surrounding left atrial myocardium, prevent-ing the formation of transmural lesions by applications ofenergy, and consequently making it difficult or impossible tocreate conduction block across the isthmus. Also, relevant isthe unpredictable content of atrial myocardium due to theexistence of extrapectinate muscles extending inferiorly fromthe appendage in the area of the isthmus, which may causeentrapping of the tip of the ablation catheter (Figs. 9, 10, and11), potentially leading to excessive tissue heating, isthmusperforation, and tamponade [3]. These anatomic observationscan be explained by the regional differences in thickness of theleft atrial wall at the level of the isthmus (Table 2).

The Myoarchitecture of the Left Atrial Wallsand Interatrial Muscular Connections

Detailed transmural dissections of the atrial wall have shown acomplex architecture of overlapping cardiomyocytes, with

Fig. 11 a Sagittal section through the left atrium and esophagus (Eso)showing the ostium of the LAA, the orifices of the left pulmonary veinsand the mitral isthmus (double-headed arrow). b–d Longitudinal histo-logical sections (Masson’s trichrome stain) through the mitral isthmus toillustrate its anatomic relations with the CS or GCVand LCx. Note in b

the space between the pectinate muscles where the left atrial wallbecomes thinner (double red arrows). Note also in b and c that a muscularcontinuity (stars) between the sleeve of the coronary sinus and left atrialwall. Ao aorta, LI left inferior pulmonary vein, LS left superior pulmonaryvein, MV mitral valve, PT pulmonary trunk, VOM vein of Marshall

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 139

different orientations giving the false impression of layers, asthese are not separated by sheaths of insulating fibrous tissue[4, 48, 62]. There are individual variations from heart to heartbut, in general, the myoarchitecture conforms to the patternfirst shown so elegantly in human hearts by Papez in 1920[49]. From the epicardial aspect, it is common to find a broadmuscular bundle that runs along the anterior atrial wall.Known as Bachmann’s bundle, or the interatrial band, it iscomposed of cardiomyocytes that are aligned in parallel

fashion relative to the plane of the atrioventricular junction(Fig. 12). Bachmann’s bundle extends rightward to the junc-tion between the right atrium and the superior caval vein.Changes in the musculature of Bachmann’s bundle couldblock or prolong interatrial conduction, resulting in abnormalatrial excitability, atrial dysfunction, atrial fibrillation, andother arrhythmias. Although Bachmann’s bundle and its vas-cular supply can easily be detected by 64 cardiac MDCT,Bachmann’s bundle is less visible in patients with severe

Fig. 12 Serial dissections to display the atrial myoarchitecture in anormal human heart. Broken lines highlight the major orientations. a, bCross-histological section, Masson’s trichrome stain. Show the Bach-mann’s bundle crossing the anterior interatrial groove and branchingtoward the atrial appendages. c Bachmann’s bundle combines with thesuperficial circular fibers passing to the left lateral wall (yellow brokenlines). d–f Shows the longitudinal fibers of the septopulmonary bundle(yellow broken lines), which arises from the interatrial groove underneathBachmann’s bundle, fanning out to line the pulmonary veins and to passlongitudinally over the dome (d), in the posterior wall of the left atriumand the superficial circular fibers in the inferior wall (e and f). Note in eand f muscular bridges (arrow) across the posterior interatrial groove (e)and inferior interatrial connections (arrow) through the CS. g Show a

deeper dissection showing the myoarchitecture in the subendocardium.The septoatrial bundle (red broken lines), arises from the anterior septalraphe underneath Bachmann’s bundle and its myocytes run obliquely inthree directions: across the dome of the left atrium, also pass leftward intothe lateral wall, and others continue into the fine ridges lining the cavity ofthe LAA. h Cross-histological section (Masson’s trichrome stain) showsthe Bachmann bundle and its rightward extensions (arrow) toward thesinus node. i Cross-histological section (Masson’s trichrome stain) show-ing a muscular bridge (arrow) across the anterior interatrial groove. ICVinferior caval vein, LA left atrium, LAA left atrial appendage, LI leftinferior pulmonary vein, LS left superior pulmonary vein, LV left ventri-cle, OF oval fossa, RAA right atrial appendage, RI right inferior pulmo-nary vein, RS right superior pulmonary vein, SCV superior caval vein

140 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

coronary artery disease, atrial fibrillation, and interatrialconduction block. In the absence of Bachmann’s bundle,the area is replaced by fat. Thus, this suggests anassociation between the above conditions and diseasedBachmann’s bundle fibers [63].

Deep to Bachmann’s bundle, and inferior to it, are cardio-myocytes arising from the anterior rim of the oval fossa. Theseblend into Bachmann’s bundle, and pass leftward to the lateralwall of the left atrium, passing to either side of the neck of theleft appendage, and then reuniting as a broad band that runscircumferentially around the inferior wall to enter the posteriorseptal raphe (Fig. 12). Another important bundle, composedof longitudinally to obliquely arranged cardiomyocytes, arisesfrom the anterosuperior septal raphe, and passes beneathBachmann’s bundle onto the surface of the atrial roof. Thesecardiomyocytes were described by Papez as the septopulmo-nary bundle [49]. They fan out to pass in front, between, andbehind the insertions of the pulmonary veins, joining with thevenous muscular sleeves (Fig. 12). On the posterior wall, theseptopulmonary bundle often has two diverging branches thatfuse with, and become indistinguishable from, the circumfer-ential cardiomyocytes coming from the lateral wall.

Deeper than the septopulmonary bundle and forming thesubendocardium is the septoatrial bundle described byPapez [49] (Fig. 12). This bundle arises from the anteriorseptal raphe as an array of obliquely arranged cardiomyo-cytes. These combine with the oblique cardiomyocytes fromthe anterior vestibule, and those from the septopulmonarybundle to the atrial roof, continuing between the orifices ofthe left and right pulmonary veins on the posterior wall ofthe left atrium (Fig. 12). It is common to find extensionsfrom the septoatrial bundle forming loops around the area ofthe venoatrial junctions, and often these can be traced to thecircular cardiomyocytes of the venous sleeves. In somecases, however, the subendocardial cardiomyocytes are lon-gitudinal, running along the long axis of the vein, while thesubepicardial cardiomyocytes encircle the veins. Branchesfrom the septoatrial bundle also pass leftward into the lateralwall. Some of the cardiomyocytes encircle the mouth of theleft appendage, while others continue into the fine ridgeslining the cavity of the appendage.

Apart frommuscular continuity at the margins and the floorof the oval fossa, there are other muscular bundles that permitconduction between the atria. In the majority of hearts, themost obvious muscular interatrial bridge is Bachmann’s bun-dle. Its rightward and leftward communications fan out toblend into musculature of the atrial walls. Its rightward com-munications, nonetheless, are mainly on the epicardial side ofthe terminal crest anterior to the mouth of the superior cavalvein and close to the site of the sinus node (Fig. 12). It is theproximity of Bachman’s bundle to the crest, and the site of thenode, which makes this the most significant electrical intera-trial connection. Additionally, in some hearts, Bachmann’s

bundle can coexist with muscular bridges across the anteriorinteratrial groove [1]. Another structure that allows connec-tions between the atria is the coronary sinus. The sinus runsalong the posteroinferior wall of the left atrium, on the atrialside of the true atrioventricular junction [64] (Figs. 11 and 12).In all specimens examined, the venous wall of the sinus wassurrounded by a sleeve of myocardium extending, in somecases, almost 5 cm from the right atrial orifice [65]. Myocar-dial connections of varying in number and morphology leftthis muscular sleeve and connected to the wall of the leftatrium (Figs. 11 and 12). The right atrial orifice of the sinusabuts the superior margin of the right atrioventricular junctionand the inferior paraseptal mitral annulus in the pyramidalspace (Figs. 4, 5, and 6). The inferior interatrial connectionsthrough the walls of the sinus may explain the need foradditional ablation in and on the venous channel so as to cureatrial fibrillation [65]. In addition, from the perspective ofablationists, the coronary sinus is an important channel formapping and for reaching accessory atrioventricular pathwaysaround the mitral valve and those traversing the inferior pyra-midal space (the inferior paraseptal pathways). The orifice ofthe coronary sinus may be accessed also for ablating the slowpathway in patients with atrioventricular nodal re-entranttachycardia. The coronary sinus is used as a conduit forcatheter treatment of arrhythmias as well as left ventricularpacing during cardiac resynchronizarion therapy. To obtainrecordings of the left atrium and left ventricle, a catheter isguided into the coronary sinus. Because of the sharp angle ofthe coronary sinus with the left atrium, catheterization of thisstructure is easier via the superior caval vein (Table 2).

Important Structures in the Neighborhood of the Atria

Relationship between the Esophagus and Left Atrium

Due to the close proximity of the esophagus to the posteriorwall of the left atrium [35] (Fig. 13), ablative proceduresinvolving this region of the atrium may cause esophagealdamage, resulting some times in the formation of an atrialeso-phageal fistula [66]. Computed tomography is a valuable toolfor showing the relationship between the atrial wall and theesophagus or the descending aorta prior to undertaking theablation procedure [67]. Peristalsis, however, and dynamicmovement of the esophagus during the procedure, can resultin discordance between the preprocedural and intraproceduralanatomy. In an anatomical study, we found that the length ofthe esophagus in contact with the posterior left atrium rangedfrom 30 to 53 mm, with a mean of 42±7 mm. The esophaguswas within 5 mm of the endocardium of the posterior left atrialwall in two fifths of the specimens [35]. Behind the posteriorwall is a layer of fibrous pericardium, along with fibro-fattytissue of irregular thickness that contains esophageal arteries

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 141

and the plexus formed by the vagus nerve (Fig. 13). Theseanatomic structures may be affected by ablative procedures.The vagus nerves pass behind the root of the lungs, and formright and left posterior pulmonary plexuses. From the caudalpart of the left pulmonary plexus, two branches descend on theanterior surface of the esophagus (Fig. 13) joining with abranch from the right pulmonary plexus to form the anterioresophageal plexus. The posterior and anterior esophageal plex-uses enter the abdomen through the esophageal diaphragmaticopening, reuniting to become the posterior and anterior vagaltrunks that innervate the stomach and pyloric canal, along withthe digestive tract as far as the proximal part of the colon. Ourobservations on postmortem hearts revealed a mean distancebetween the bundles of the anterior esophageal plexus andposterior left atrial endocardium, or veno-atrial junctions, of4.1±1.4 mm with a range from 2.5 to 6.5 mm [68].

Relationship between the Phrenic Nerves and the Atria

The phrenic nerves lie along the lateral mediastinum, andrun from the thoracic inlet to the diaphragm [69]. The rightphrenic nerve has a close anatomical relationship with thesuperior caval vein, with a minimal distance between them

of 0.3±0.5 mm, while the minimal distance to the rightsuperior pulmonary vein is 2.1±0.4 mm (Fig. 13). In onethird of human heart specimens, the anterior wall of the rightsuperior pulmonary vein was within 2 mm of the nerve [69].Consequently, catheter ablation aimed at modifying thefunction of the sinus node at the lateral right atrium, andcatheter ablation for atrial fibrillation at the orifice andadjacent area of the right superior pulmonary vein, carry acertain risk of damaging the right phrenic nerve [70].

The left phrenic nerve descends on the fibrous pericardium,taking one of three courses. It runs over the anterior surface ofthe left ventricle in one fifth of the population, over the lateralmargin of the left ventricle in three fifths, and in a poster-oinferior direction in the remainder [71]. Computed tomo-graphic angiography can demonstrate the left phrenicneurovascular bundle as it passes over the pericardium cover-ing the left ventricle in three quarters of the studies [72]. It isdifficult to image the right phrenic nerve, but high outputpacing causing diaphragmatic contractions can be used tomark its course. During electrophysiologic interventions, theleft nerve is especially at risk when procedures are performedin the vicinity of the left atrial appendage (Fig. 13). In a studyof cadavers, the endocardium of the roof of the left appendage

Fig. 13 a Left atrium view from the back after removal of thedescending thoracic aorta to show the course of the Eso in situ andits relationship to the vagus nerves. b An overview of a transthoracicsection through the mediastinum showing the locations of the esoph-agus and descending aorta relative to the right pulmonary veins and leftatrium. c Cross-histological section (Masson’s trichrome stain) show-ing the proximity of the esophagus to middle of the posterior wall ofthe left atrium. d This dissection shows an anterior view of the heartwith the fibrous pericardium around it. The lungs were removed. Note

the course of the right phrenic nerve. e Histological sections (Masson’strichrome stain) through the right superior pulmonary vein (RS) andright venoatrial junction. The right phrenic nerve is adherent to thefibrous pericardium. Note the short distance between the endocardiumof the RS and the right phrenic nerve. f Left lateral view of the heartshowing the close anatomic relation of the left phrenic nerve with theLAA and the lateral wall of the LV to penetrate into the left part of thediaphragm. LI left inferior pulmonary vein, LS left superior pulmonaryvein, PT pulmonary trunk, RI right inferior pulmonary vein

142 J. of Cardiovasc. Trans. Res. (2013) 6:124–144

was within 4 mm of the left nerve in one tenth of specimens.Regardless of the position of the nerve in relation to the highleft ventricular wall, it was within 3 mm of the epicardialsurface in just over one third of the specimens [69] (Fig. 13),and passes at a distance of less than 3 mm of left marginal veinin 43% of cadaveric heart specimens [69]. Given the anatomicvariability of the target coronary veins for cardiac resynchro-nizarion therapy, and close proximity of the left phrenic nerveto these structures, cardiac MDCT can be crucial in demon-strating this relationship in order to avoid the phrenic nerveduring LV lead placement [72] (Table 2).

Acknowledgments This study was supported by the Centro Nacionalde Investigaciones Cardiovasculares (C.N.I.C.) 2008–11 (to DSQ andJAC), Spain.

References

1. Ho, S. Y., Sánchez-Quintana, D., Cabrera, J. A., & Anderson, R.H. (1999). Anatomy of the left atrium: implications for radiofre-quency ablation of atrial fibrillation. Journal of CardiovascularElectrophysiology, 10, 1525–1533.

2. Sánchez-Quintana, D., Anderson, R. H., Cabrera, J. A., et al.(2002). The terminal crest: morphological features relevant toelectrophysiology. Heart, 88, 406–411.

3. Cabrera, J. A., Ho, S. Y., Climent, V., & Sánchez-Quintana, D.(2008). The architecture of the left lateral atrial wall: a particularanatomic region with implications for ablation of atrial fibrillation.European Heart Journal, 29, 356–362.

4. Ho, S. Y., Anderson, R. H., & Sánchez-Quintana, D. (2002). Atrialstructure and fibres: morphologic bases of atrial conduction.Cardiovascular Research, 54, 325–336.

5. Ho, S. Y., & Sánchez-Quintana, D. (2009). The importance ofatrial structure and fibers. Clinical Anatomy, 22, 52–63.

6. Anderson, R. H., & Cook, A. C. (2007). The structure and com-ponents of the atrial chambers. Europace, 9(Suppl 6), vi3–vi9.

7. Su, P., McCarthy, K. P., & Ho, S. Y. (2008). Occluding the left atrialappendage: anatomical considerations. Heart, 94, 1166–1170.

8. Matsuyama, T. A., Inoue, S., Tanno, K., et al. (2004). Anatomicaldiversity and age-related histological changes in the human rightatrial posterolateral wall. Europace, 6, 307–315.

9. Gami, A. S., Edwards, W. D., Lachman, N., et al. (2010).Electrophysiological anatomy of typical atrial flutter: the posteriorboundary and causes for difficulty with ablation. Journal ofCardiovascular Electrophysiology, 21, 144–149.

10. Becker, A. E. (2004). How structurally normal are human atria inpatients with atrial fibrillation? Heart Rhythm, 1, 627–631.

11. Olgin, J. E., Kalman, J. M., Fitzpatrick, A., et al. (1995). Role of rightatrial endocardial structures as barriers to conduction during humantype I atrial flutter: activation and entrainment mapping guided byintracardiac echocardiography. Circulation, 92, 1839–1848.

12. Saoudi, N., Cosio, F., Waldo, A., et al. (2001). Classification ofatrial flutter and regular atrial tachycardia according to electro-physiologic mechanism and anatomic bases: a statement from ajoint expert group from the Working Group of Arrhythmias of theEuropean Society of Cardiology and the North American Societyof Pacing and Electrophysiology. Journal of CardiovascularElectrophysiology, 12, 852–866.

13. Keith, A., & Flack, M. (1907). The form and nature of the mus-cular connections between the primary divisions of the vertebrateheart. Journal of Anatomy and Physiology, 41, 172–189.

14. Truex, R. C., Smythe, M. Q., & Taylor, M. J. (1967). Reconstructionof the human sinoatrial node. Anatomical Record, 159, 371–378.

15. Chandler, N. J., Greener, I. D., Tellez, J. O., et al. (2009).Molecular architecture of the human sinus node: insights into thefunction of the cardiac pacemaker. Circulation, 119, 1562–1575.

16. Sánchez-Quintana, D., Cabrera, J. A., Farré, J., et al. (2005). Sinusnode revisited in the era of electroanatomical mapping and catheterablation. Heart, 91, 189–194.

17. Inoue, S., Shinohara, F., Niitani, H., & Gotoh, K. (1986). A newmethod for the histological study of aging changes in the sinoatrialnode. Japanese Heart Journal, 27, 653–660.

18. Lin, W. S., Tai, C. T., Hsieh, M. H., et al. (2003). Catheter ablationof paroxysmal atrial fibrillation initiated by non-pulmonary veinectopy. Circulation, 107, 3176–3183.

19. Ho, S. Y., & Anderson, R. H. (2000). How constant anatomically isthe tendon of Todaro as a marker for the triangle of Koch? Journalof Cardiovascular Electrophysiology, 11, 83–89.

20. Posan, E., Gula, L. J., Skanes, A. C., et al. (2006). Characteristicsof slow pathway conduction after successful AVNRT ablation.Journal of Cardiovascular Electrophysiology, 17, 847–851.

21. Anderson, R. H., Yanni, J., Boyett, M. R., et al. (2009). The anatomyof the cardiac conduction system. Clinical Anatomy, 22, 99–113.

22. Inoue, S., & Becker, A. E. (1998). Posterior extensions of thehuman compact atrioventricular node: a neglected anatomic fea-ture of potential clinical significance. Circulation, 97, 188–193.

23. Sánchez-Quintana, D., Picazo-Angelín, B., Cabrera, A., et al.(2010). Koch’s triangle and the atrioventricular node in Ebstein’sanomaly: implications for catheter ablation. Revista Española deCardiología, 63, 660–667.

24. Sánchez-Quintana, D., Ho, S. Y., Cabrera, J. A., et al. (2001).Topographic anatomy of the inferior pyramidal space: relevanceto radiofrequency catheter ablation. Journal of CardiovascularElectrophysiology, 12, 210–217.

25. Jazayeri, M. R., Hempe, S. L., Sra, J. S., et al. (1992). Selectivetranscatheter ablation of the fast and slow pathways using radio-frequency energy in patients with atrioventricular nodal re-entranttachycardia. Circulation, 85, 1318–1328.

26. Cauchemez, B., Haïssaguerre, M., Fischer, B., et al. (1996).Electrophysiological effects of catheter ablation of inferior venacava-tricuspid annulus isthmus in common atrial flutter. Circulation,93, 284–294.

27. Heidbüchel, H., Willems, R., & van Rensburg, H. (2000). Rightatrial angiographic evaluation of the posterior isthmus: relevancefor ablation of typical atrial flutter. Circulation, 101, 2178–2184.

28. Cabrera, J. A., Sánchez-Quintana, D., Farré, J., et al. (2005). Theinferior right atrial isthmus: further architectural insights for cur-rent and coming ablation technologies. Journal of CardiovascularElectrophysiology, 16, 409–410.

29. Da Costa, A., Faure, E., Thévenin, J., et al. (2004). Effect of isthmusanatomy and ablation catheter on radiofrequency catheter ablation ofthe cavotricuspid isthmus. Circulation, 110, 1030–1035.

30. Da Costa, A., Mourot, S., Roméyer-Bouchard, C., et al. (2004).Anatomic and electrophysiological differences between chronic andparoxysmal forms of common atrial flutter and comparison withcontrols. Pacing and Clinical Electrophysiology, 27, 1202–1211.

31. Chang, S. L., Tai, C. T., Lin, Y. J., et al. (2007). The electro-anatomic characteristics of the cavotricuspid isthmus: implicationsfor the catheter ablation of atrial flutter. Journal of CardiovascularElectrophysiology, 18, 18–22.

32. Saremi, F., Pourzand, L., Krishnan, S., et al. (2008). Right atrialcavotricuspid isthmus: anatomic characterization with multi-detector row CT. Radiology, 247, 658–668.

33. Schwinger, M. E., Tunick, P. A., Freedberg, R. S., & Kronzon, I.(1990). Vegetations on endocardial surfaces struck by regurgitantjets: diagnosis by transesophageal echocardiography. AmericanHeart Journal, 119, 1212–1215.

J. of Cardiovasc. Trans. Res. (2013) 6:124–144 143

34. Platonov, P. G., Ivanov, V., Ho, S. Y., & Mitrofanova, L. (2008).Left atrial posterior wall thickness in patients with and withoutatrial fibrillation: data from 298 consecutive autopsies. Journal ofCardiovascular Electrophysiology, 19, 689–692.

35. Sánchez-Quintana, D., Cabrera, J. A., Climent, V., et al. (2005).Anatomic relations between the esophagus and left atrium and rele-vance for ablation of atrial fibrillation. Circulation, 112, 1400–1405.

36. Scharf, C., Sneider, M., Case, I., et al. (2003). Anatomy of thepulmonary veins in patients with atrial fibrillation and effects ofsegmental ostial ablation analyzed by computed tomography.Journal of Cardiovascular Electrophysiology, 14, 150–155.

37. Cronin, P., Sneider, M. B., Kazerooni, E. A., et al. (2004). MDCTof the left atrium and pulmonary veins in planning radiofrequencyablation for atrial fibrillation: a how-to guide. AJR. AmericanJournal of Roentgenology, 183, 767–778.

38. Tsao, H. M., Wu,M. H., Yu,W. C., et al. (2001). Role of right middlepulmonary vein in patients with paroxysmal atrial fibrillation.Journal of Cardiovascular Electrophysiology, 12, 1353–1357.

39. Marom, E. M., Herndon, J. E., Kim, Y. H., et al. (2004). Variationsin pulmonary venous drainage to the left atrium: implications forradiofrequency ablation. Radiology, 230, 824–829.

40. Ho, S. Y., Cabrera, J. A., & Sánchez-Quintana, D. (2004).Anatomy of the pulmonary vein-atrium junction. In S. A. Chen,M. Haïssaguerre, & D. P. Zipes (Eds.), Thoracic vein arrhythmias.Mechanisms and treatment (pp. 42–53). Oxford: Blackwell.

41. Haïssaguerre, M., Jaïs, P., Shah, D. C., et al. (1998). Spontaneousinitiation of atrial fibrillation by ectopic beats originating in thepulmonary veins. New England Journal of Medicine, 339, 659–666.

42. Nathan, H., & Eliakim, M. (1966). The junction between the leftatrium and the pulmonary veins. An anatomic study of humanhearts. Circulation, 34, 412–422.

43. Ho, S. Y., Cabrera, J. A., Tran, V. H., et al. (2001). Architecture ofthe pulmonary veins: relevance to radiofrequency ablation. Heart,86, 265–270.

44. Cabrera, J. A., Ho, S. Y., Climent, V., et al. (2009). Morphologicalevidence of muscular connections between contiguous pulmonaryvenous orifices: relevance of the interpulmonary isthmus for cath-eter ablation in atrial fibrillation. Heart Rhythm, 6, 1192–1198.

45. Vaquero, M., Calvo, D., & Jalife, J. (2008). Cardiac fibrillation: fromion channels to rotors in the human heart.Heart Rhythm, 5, 872–879.

46. Vaitkevicius, R., Saburkina, I., Rysevaite, K., et al. (2009). Nervesupply of the human pulmonary veins: an anatomical study. HeartRhythm, 6, 221–228.

47. Takahashi, A., Kuwahara, T., & Takahashi, Y. (2009). Complicationsin the catheter ablation of atrial fibrillation: incidence and manage-ment. Circulation Journal, 73, 221–226.

48. Keith, A. (1907). An account of the structures concerned in theproduction of the jugular pulse. Journal of Anatomy andPhysiology, 42, 1–25.

49. Papez, J. W. (1920). Heart musculature of the atria. The AmericanJournal of Anatomy, 27, 255–285.

50. Mansour, M., Refaat, M., Heist, E. K., et al. (2006). Three-dimensional anatomy of the left atrium by magnetic resonanceangiography: implication for catheter ablation for atrial fibrillation.Journal of Cardiovascular Electrophysiology, 17, 719–723.

51. de Oliveira, I. M., Scanavacca, M. I., Correia, A. T., et al. (2007).Anatomic relations of theMarshall vein: importance for catheterizationof the coronary sinus in ablation procedures. Europace, 9, 915–919.

52. von Lüdinghausen, M. (2003). The venous drainage of the humanmyocardium. Advances in Anatomy, Embryology and Cell Biology,168(I-VIII), 1–104.

53. Saremi, F., Muresian, H., & Sánchez-Quintana, D. (2012). Coronaryveins: comprehensive CT-anatomic classification and review of var-iants and clinical implications. Radiographics, 32, E1–E32.

54. Hwang, C., Wu, T. L., Doshi, R. N., et al. (2000). Vein of Marshallcannulation for the analysis of electrical activity in patients withfocal atrial fibrillation. Circulation, 101, 1503–1508.

55. Choi, E. K., Shen, M. J., Han, S., et al. (2010). Intrinsic cardiacnerve activity and paroxysmal atrial tachyarrhythmia in ambulato-ry dogs. Circulation, 121, 2615–2623.

56. Veinot, J., Harrity, P., Gentile, F., et al. (1997). Anatomy of thenormal left atrial appendage. A quantitative study of age-relatedchanges in 500 autopsy hearts: implications for echocardiographicexamination. Circulation, 96, 3112–3115.

57. Wongcharoen, W., Tsao, H. M., Wu, M. H., et al. (2006).Morphologic characteristics of the left atrial appendage, roof,and septum: implicat ion. Journal of CardiovascularElectrophysiology, 17, 951–956.

58. Qamruddin, S., Shinbane, J., Shriki, J., et al. (2010). Left atrialappendage: structure, function, imaging modalities and therapeuticoptions. Expert Review of Cardiovascular Therapy, 8, 65–75.

59. Jaïs, P., Hocini, M., Hsu, L. F., et al. (2004). Technique and results oflinear ablation at the mitral isthmus. Circulation, 110, 2996–3002.

60. Becker, A. E. (2004). Left atrial isthmus: anatomic aspects relevantfor linear catheter ablation procedures in humans. Journal ofCardiovascular Electrophysiology, 15, 809–812.

61. Wittkampf, F. H., van Oosterhout, M. F., Loh, P., et al. (2005).Where to draw the mitral isthmus line in catheter ablation of atrialfibrillation: histological analysis. European Heart Journal, 26,689–695.

62. Wang, K., Ho, S. Y., Gibson, D. G., & Anderson, R. H. (1995).Architecture of atrial musculature in humans. British HeartJournal, 73, 559–565.

63. Saremi, F., Channual, S., Krishnan, S., et al. (2008). Bachmannbundle and its arterial supply: Imaging with multidetector CT—implications for interatrial conduction abnormalities and arrhyth-mias. Radiology, 248, 447–457.

64. Ho, S. Y., Cabrera, J. A., & Sánchez-Quintana, D. (2012). Leftatrial anatomy revisited. Circulation: Arrhythmia andElectrophysiology, 5, 220–228.

65. Chauvin, M., Shah, D. C., Haïssaguerre, M., et al. (2000). Theanatomic basis of connections between the coronary sinus muscu-lature and the left atrium in humans. Circulation, 101, 647–652.

66. Cummings, J. E., Schweikert, R. A., Saliba, W., et al. (2006). Briefcommunication: atrial-esophageal fistulas after radiofrequency ab-lation. Annals of Internal Medicine, 144, 572–574.

67. Lemola, K., Sneider, M., Desjardins, B., et al. (2004). Computedtomographic analysis of the anatomy of the left atrium and theesophagus: implications for left atrial catheter ablation.Circulation, 110, 3655–3660.

68. Ho, S. Y., Cabrera, J. A., & Sánchez-Quintana, D. (2006). Vagariesof the vagus nerve: relevance to ablationists. Journal ofCardiovascular Electrophysiology, 17, 330–331.

69. Sánchez-Quintana, D., Cabrera, J. A., Climent, V., et al. (2005). Howclose are the phrenic nerves to cardiac structures? Implicationsfor cardiac interventionalists. Journal of CardiovascularElectrophysiology, 16, 309–313.

70. Lee, B. K., Choi, K. J., Kim, J., et al. (2004). Right phrenic nerveinjury following electrical disconnection of the right superior pulmo-nary vein. Pacing and Clinical Electrophysiology, 27, 1444–1446.

71. Sánchez-Quintana, D., Ho, S. Y., Climent, V., Murillo, M., &Cabrera, J. A. (2009). Anatomic evaluation of the left phrenicnerve relevant to epicardial and endocardial catheter ablation:implications for phrenic nerve injury. Heart Rhythm, 6, 764–768.

72. Matsumoto, Y., Krishnan, S., Fowler, S. J., et al. (2007). Detectionof phrenic nerves and their relation to cardiac anatomy using 64-slice multidetector computed tomography. The American Journalof Cardiology, 100, 133–137.

144 J. of Cardiovasc. Trans. Res. (2013) 6:124–144