We are searching data for your request:
Upon completion, a link will appear to access the found materials.
When assessing an ECG we divide our 12-lead into four main contiguous lead groups: inferior, lateral, septal, and anterior. Regions not well represented on a standard 12-lead are the posterior region and the right ventricle, So if there is an infarction in these regions how we can determine it ?
The 2 main coronary arteries are the left main and right coronary arteries.
Left main coronary artery (LMCA). The left main coronary artery supplies blood to the left side of the heart muscle (the left ventricle and left atrium). The left main coronary divides into branches:
The left anterior descending artery branches off the left coronary artery and supplies blood to the front of the left side of the heart.
The circumflex artery branches off the left coronary artery and encircles the heart muscle. This artery supplies blood to the outer side and back of the heart.
Right coronary artery (RCA). The right coronary artery supplies blood to the right ventricle, the right atrium, and the SA (sinoatrial) and AV (atrioventricular) nodes, which regulate the heart rhythm. The right coronary artery divides into smaller branches, including the right posterior descending artery and the acute marginal artery. Together with the left anterior descending artery, the right coronary artery helps supply blood to the middle or septum of the heart.
Smaller branches of the coronary arteries include: obtuse marginal (OM), septal perforator (SP), and diagonals.
Genetic and Developmental Basis of Congenital Cardiovascular Malformations
During the fifth week, ridges of the subendocardial tissue form in the bulbus cordis . Similar ridges also form in the truncus arteriosus and are continuous with those in the bulbus cordis. The spiral orientation of the ridges results in a spiral aorticopulmonary septum when these ridges fuse. This septum divides the bulbus cordis and the truncus arteriosus into two channels, the aorta and the pulmonary trunk. Blood from the aorta now passes into the third and fourth pairs of aortic arch arteries (future aortic arch) and blood from the pulmonary trunk flows into the sixth pair of aortic arch arteries (future pulmonary arteries). Several mouse mutants including disheveled-2, semaphorin3C, and c-Jun exhibit failure of aorticopulmonary septation ( Hamblet et al., 2002 Feiner et al., 2001 Eferl et al., 1999 ). Various combinations of the RAR alpha 1, RAR beta, and RXR alpha gene mutations also result in muscular ventricular septal defects, double outlet right ventricle, transposition, and truncus arteriosus ( Lee et al., 1997 ). In addition, mutations in Fgf8 and Tbx1 ( Frank et al., 2002 Vitelli et al., 2002 Jerome and Papaioannou, 2001 ) demonstrate common outflow tract developmental abnormalities that are suggestive of the type seen in DiGeorge syndrome. Moreover, mutation of Pitx2c isoform provides functional evidence that the anterior heart field contributes to the common outflow tract and aortic arch remodeling ( Liu et al., 2002 ).
Introduction. I—Leads, rate, rhythm, and cardiac axis
Electrocardiography is a fundamental part of cardiovascular assessment. It is an essential tool for investigating cardiac arrhythmias and is also useful in diagnosing cardiac disorders such as myocardial infarction. Familiarity with the wide range of patterns seen in the electrocardiograms of normal subjects and an understanding of the effects of non-cardiac disorders on the trace are prerequisites to accurate interpretation.
The contraction and relaxation of cardiac muscle results from the depolarisation and repolarisation of myocardial cells. These electrical changes are recorded via electrodes placed on the limbs and chest wall and are transcribed on to graph paper to produce an electrocardiogram (commonly known as an ECG).
The sinoatrial node acts as a natural pacemaker and initiates atrial depolarisation. The impulse is propagated to the ventricles by the atrioventricular node and spreads in a coordinated fashion throughout the ventricles via the specialised conducting tissue of the His-Purkinje system. Thus, after delay in the atrioventricular mode, atrial contraction is followed by rapid and coordinated contraction of the ventricles.
The electrocardiogram is recorded on to standard paper travelling at a rate of 25 mm/s. The paper is divided into large squares, each measuring 5 mm wide and equivalent to 0.2 s. Each large square is five small squares in width, and each small square is 1 mm wide and equivalent to 0.04 s.
Throughout this article the duration of waveforms will be expressed as0.04 s = 1 mm = 1 small square
The electrical activity detected by the electrocardiogram machine is measured in millivolts. Machines are calibrated so that a signal with an amplitude of 1 mV moves the recording stylus vertically 1 cm. Throughout this text, the amplitude of waveforms will be expressed as: 0.1 mV = 1 mm = 1 small square.
The amplitude of the waveform recorded in any lead may be influenced by the myocardial mass, the net vector of depolarisation, the thickness and properties of the intervening tissues, and the distance between the electrode and the myocardium. Patients with ventricular hypertrophy have a relatively large myocardial mass and are therefore likely to have high amplitude waveforms. In the presence of pericardial fluid, pulmonary emphysema, or obesity, there is increased resistance to current flow, and thus waveform amplitude is reduced.
The direction of the deflection on the electrocardiogram depends on whether the electrical impulse is travelling towards or away from a detecting electrode. By convention, an electrical impulse travelling directly towards the electrode produces an upright (“positive”) deflection relative to the isoelectric baseline, whereas an impulse moving directly away from an electrode produces a downward (“negative”) deflection relative to the baseline. When the wave of depolarisation is at right angles to the lead, an equiphasic deflection is produced.
The six chest leads (V1 to V6) “view” the heart in the horizontal plane. The information from the limb electrodes is combined to produce the six limb leads (I, II, III, aVR, aVL, and aVF), which view the heart in the vertical plane. The information from these 12 leads is combined to form a standard electrocardiogram.
The arrangement of the leads produces the following anatomical relationships: leads II, III, and aVF view the inferior surface of the heart leads V1 to V4 view the anterior surface leads I, aVL, V5, and V6 view the lateral surface and leads V1 and aVR look through the right atrium directly into the cavity of the left ventricle.
Why does the posterior region and the right ventricle of the heart are not well represented in standard 12 leads? - Biology
In general ventricular tachycardias have wide QRS complexes. One of the earliest descriptions of ventricular tachycardia (VT) with a narrow QRS complex was by Cohen et al in 1972.1 Their description was a left posterior fascicular tachycardia with relatively narrow QRS. In 1979, Zipes et al2 reported three patients with ventricular tachycardia characterized by QRS width of 120 to 140 ms, right bundle branch block morphology and left-axis deviation. These patients were young and had no major cardiac abnormalities. The arrhythmia could be induced by exercise, atrial and ventricular premature beats as well as atrial pacing and ventricular pacing. Belhassen et al observed that this tachycardia can be terminated by the calcium channel blocker verapamil3 This observation has been confirmed subsequently by others as well.4,5,6,7 Belhassen et al proposed that this is a specific ECG-electrophysiological entity.8 Fascicular tachycardia has also been called Idiopathic Left Ventricular Tachycardia (ILVT) by other authors, though left ventricular outflow tract VT also comes under the purview of this term.9,10 Fascicular tachycardia is usually paroxysmal, but a case which was persistent, leading to cardiac enlargement and complete resolution following therapy with verapamil has also been reported.4 Termination of idiopathic fascicular ventricular tachycardia by vagal maneuvers was noted in 4 cases by Buja et al.11 Successful radiofrequency catheter ablation was described by Klein et al.12 In this article we propose to review the current status of our knowledge regarding the genesis and treatment of idiopathic fascicular ventricular tachycardia.
Mechanism and Classification
Zipes et al postulated that the origin of the tachycardia was localized to a small region of reentry or triggered automaticity located in the posteroinferior left ventricle, close to the posterior fascicle of the left bundle branch.2 Response to verapamil suggested a role for the slow inward calcium channel in the genesis of the arrhythmia. Endocardial mapping during tachycardia revealed the earliest activation at the ventricular apex and mid septum.13 The tachycardia can be entrained by ventricular and atrial pacing. Entrainment by atrial pacing suggests easy access over the conduction system into the reentry circuit and hence a role for the fascicles in the reentrant circuit.14 Lau suggested the origin as reentry circuits involving the lower septum or posterior part of the left ventricle close to the endocardial surface in view of the response to radiofrequency ablation in these sites.15 Purkinje potential recorded in the diastolic phase during VT at the mid-anterior left ventricular septum in rare cases with RBBB pattern and right axis deviation suggested origin near left anterior fascicle in those cases.16
Recently Kuo et al has questioned the involvement of the fascicle of the left bundle branch in ILVT. 17 They studied two groups of patients with ILVT. One with left anterior or posterior fascicular block during sinus rhythm and the other without. They noted that the transition zone of QRS complexes in the precordial leads were similar during VT in both groups. New fascicular blocks did not appear after ablation. Therefore they concluded that the fascicle of the left bundle branch may not be involved in the anterograde limb of reentrant circuit in ILVT.
Fascicular tachycardia has been classified into three subtypes: (1) left posterior fascicular VT (Figure 1) with a right bundle branch block (RBBB) pattern and left axis deviation (common form) (2) left anterior fascicular VT with RBBB pattern and right-axis deviation (uncommon form) and (3) upper septal fascicular VT with a narrow QRS and normal axis configuration (rare form).18
Figure 1. 12 lead ECG of Idiopathic left ventricular tachycardia. It shows classical RBBB with leftward axis morphology suggestive of posterior fascicle origin.
Endocardial activation mapping during VT identifies the earliest site in the region of the infero-posterior left ventricular septum. This finding, along with VT morphology and short retrograde VH interval suggests a left posterior fascicular origin. Nakagawa and colleagues19 recorded high-frequency potentials preceding the site of earliest ventricular activation during the VT and sinus rhythm. These potentials are thought to represent activation of Purkinje fibers and are recorded from the posterior one third of the left ventricular septum. Successful RF ablation is achieved at sites where the purkinje potential is recorded 30 to 40 ms before the VT QRS complex.
Some date suggest that the tachycardia may originate from a false tendon or fibro- muscular band that extends from the posteroinferior left ventricle to the basal septum.20 Histological examination of false tendon disclosed abundant Purkinje fibers.
Fascicular tachycardia can be induced by programmed atrial or ventricular stimulation in most cases. Isoprenaline infusion may be required in certain cases rarely there may be difficulty in induction despite isoprenaline infusion. Endocardial mapping identifies the earliest activation in the posteroapical left ventricular septum in patients with posterior fascicular tachycardia.
A high frequency potential with short duration, preceding the QRS has been described as the Purkinje potential (Figure 2). This has also been called P potential and diastolic potential. P potentials can be recorded both in sinus rhythm and during ventricular tachycardia. Pacing at sites manifesting the earliest P potential produces QRS complexes identical to that of the clinical tachycardia.19
Figures 2. Intracardia electrogram during tachycardia showing purkinje potential, which persisted after the ablation also (arrow).
Intravenous verapamil is effective in terminating the tachycardia. However the efficacy of oral verapamil in preventing tachycardia relapse is variable. Good response and resolution of tachycardiomyopathy with verapamil treatment was noted by Toivonen et al4, while Chiaranda et al commented on the poor efficacy.21 Treatment with propranolol has also resulted in cure of arrhythmia and resolution of features of tachycardiomyopathy in another case with incessant fascicular VT.22 Though fascicular tachycardias do not generally respond to adenosine, termination of VT originating from the left anterior fascicle by intravenous adenosine has been documented.23
The young age of most patients with need for long-term antiarrhythmic treatment and attendant side effects prompted the search for curative therapies. Fontaine et al (1987) described successful treatment of ILVT by application of a high-energy DC shock (fulguration) between the catheter tip and a neutral plate placed under the patient's back.24 Klein et al (1992) reported cure of ILVT by radiofrequency catheter ablation.25 Since then radiofrequency has remained the procedure of choice.
Different approaches for radiofrequency ablation have been described by various authors. Nakagawa et al preferred careful localization of the Purkinje potential in guiding ablation. They selected the area where a Purkinje potential precedes the QRS complex during tachycardia.19 Wellens et recommend pace mapping with a match between the 12 simultaneously recorded ECG leads during pacing and the clinical tachycardia for localizing the site of ablation.9 They hypothesize that pathways within the Purkinje network that are not included in the reentry circuit responsible for the tachycardia may also become activated. Ablation of those regions may not result in interruption of the tachycardia circuit.
Primary Radiofrequency Ablation
Since fascicular VT is sometimes difficult to induce despite pharmacological provocation, some workers (Gupta et al) prefer primary ablation. In a recent report, seven cases of incessant fascicular VT were successfully ablated with no recurrence.26 They reported a shorter procedure time, significantly lower fluoroscopy time and lesser number of radiofrequency energy deliveries in the primary versus elective groups. The longer procedural time during elective ablation was mainly due to the time spent in induction of fascicular VT.
1. Cohen HC, Gozo EG Jr, Pick A. Ventricular tachycardia with narrow QRS complexes (left posterior fascicular tachycardia). Circulation. 1972 May 45(5): 1035-43.
2. Zipes DP, Foster PR, Troup PJ, Pedersen DH. Atrial induction of ventricular tachycardia: reentry versus triggered automaticity. Am J Cardiol. 1979 44:1-8.
3. Belhassen B, Rotmensch HH, Laniado S. Response of recurrent sustained ventricular tachycardia to verapamil. Br Heart J. 1981 Dec 46(6): 679-82.
4. Toivonen L, Nieminen M. Persistent ventricular tachycardia resulting in left ventricular dilatation treated with verapamil. Int J Cardiol. 1986 13(3): 361-5.
5. Tai YT, Chow WH, Lau CP, Yau CC. Verapamil and ventricular tachycardias. Chin Med J (Engl). 1991 Jul 104(7): 567-72.
6. Ward DE, Nathan AW, Camm AJ. Fascicular tachycardias sensitive to calcium antagonists. Eur Heart J. 19845:896-905.
7. Sethi KK, Manoharan S, Mohan JC, Gupta MP. Verapamil in idiopathic ventricular tachycardia of right bundle-branch block morphology: observations during electrophysiological and exercise testing. Pacing Clin Electrophysiol. 19869:8-16.
8. Belhassen B, Shapira I, Pelleg A, Copperman I, Kauli N, Laniado S. Idiopathic recurrent sustained ventricular tachycardia responsive to verapamil: an ECG-electrophysiologic entity. Am Heart J. 1984 Oct 108(4 Pt 1): 1034-7.
9. Wellens HJJ, Smeets JLRM. Idiopathic Left Ventricular Tachycardia: Cure by Radiofrequency Ablation. Circulation. 1993 88(6): 2978-2979.
10. Thakur RK, Klein GJ, Sivaram CA et al. Anatomic Substrate for Idiopathic Left Ventricular Tachycardia. Circulation. 199693:497-501.
11. Buja G, Folino A, Martini B et al. Termination of idiopathic ventricular tachycardia with QRS morphology of right bundle branch block and anterior fascicular hemiblock (fascicular tachycardia) by vagal maneuvers. Presentation of 4 cases. G Ital Cardiol. 1988 Jul 18(7): 560-6.
12. Klein LS, Shih H, Hackett FK, Zipes DP, Miles WM. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease. Circulation. 199285:1666-1674.
13. German LD, Packer DI, Bardy GH, Gallagher JJ. Ventricular tachycardia induced by atrial stimulation in patients without symptomatic cardiac disease. Am J Cardiol. 198352:1202-1207.
14. Okumura K, Matsuyama K, Miyagi II, Tsuchlya T, Yasue H. Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for re-entry with an area of slow conduction and effect of verapamil. Am J Cardiol. 198862:727-732.
15. Lau CP. Radiofrequency ablation of fascicular tachycardia: efficacy of pace-mapping and implications on tachycardia origin. Int J Cardiol. 1994 Oct 46(3): 255-65.
16. Nogami A, Naito S, Tada H et al. Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients. J Cardiovasc Electrophysiol. 1998 Dec 9(12): 1269-78.
17. Kuo JY, Tai CT, Chiang CE et al. Is the fascicle of left bundle branch involved in
the reentrant circuit of verapamil-sensitive idiopathic left ventricular tachycardia? Pacing Clin Electrophysiol. 2003 Oct 26(10): 1986-92.
18. Nogami A. Idiopathic left ventricular tachycardia: assessment and treatment. Card Electrophysiol Rev. 2002 Dec 6(4): 448-57.
19. Nakagawa H, Beckman KJ, McClelland JH, et al. Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential. Circulation. 199388:2607-2617.
20. Kudoh Y, Hiraga Y, Iimura O. Benign ventricular tachycardia in systemic sarcoidosis--a case of false tendon. Jpn Circ J. 1988 Apr 52(4): 385-9.
21. Chiaranda G, Di Guardo G, Gulizia M, Lazzaro A, Regolo T. Ital Heart J. 2001 Nov 2(11 Suppl): 1181-6.
22. Anselme F, Boyle N, Josephson M. Incessant fascicular tachycardia: a cause of arrhythmia induced cardiomyopathy. Pacing Clin Electrophysiol. 1998 21: 760-3.
23. Kassotis J, Slesinger T, Festic E, Voigt L, Reddy CV. Adenosine-sensitive wide-complex tachycardia: an uncommon variant of idiopathic fascicular ventricular tachycardia--a case report. Angiology. 2003 May-Jun 54(3): 369-72.
24. Fontaine G, Tonet JL, Frank R et al. Treatment of resistant ventricular tachycardia by endocavitary fulguration associated with anti-arrhythmic therapy. Eur Heart J. 1987 Aug 8 Suppl D: 133-41.
25. Klein LS, Shih H, Hackett FK, Zipes DP, Miles WM. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease. Circulation. 199285:1666-1674.
26. Gupta AK, Kumar AV, Lokhandwala YY et al. Primary radiofrequency ablation for incessant idiopathic ventricular tachycardia. Pacing Clin Electrophysiol. 2002 Nov 25(11): 1555-60.
A " complete RBBB pattern (with QRS duration > 0.11s) does not necessarily reflect the existence of a total conduction block in the right branch. This pattern only indicates that the entire or major parts of both ventricles are activated by the impulse emerging from the left branch. Thus, a significant degree of conduction delay ("high-grade" or "incomplete RBBB) can produce a similar pattern.
In pure complete RBBB, the EA should not be deviated abnormally either to the left or to the right. These axis deviations reflect coexisting fasicicular block or right ventricular hypertrophy.
Causes of RBBB Pattern
BBB is rarely a clinical problem of any consequence except when the block occurs simulanteously in both branches.
Causes of the RBBB include the following:
1. Surgical trauma from a heart operation for congenital heart diseases like a ventricular septal defect, atrial septal defect and use of catheters etc.
2. A disease which interrupts the heart fibers like a prior heart attack (myocardial infarction) causing fibrosis.
3. Chronic lung disease (cor pulmonale)
4. Elongation of the right bundle due to a congenital volume overload of the right ventricle(stretched or dilated)
5. Age associated predisposition in the elderly to sinus node dysfunction, abnormal conduction in the AV node, His-Purkinje system, and inthe bundle branches.
6. Sarcoidosis, rheumatic fever, amyloiosis, systemic lupus erythematosis, gout, familial heart block etc.
Reference:Castellanos,A. and others,Hurst's The Heart 8th Edition,The Resting Electrocardiogram,321-356.
Incomplete RBBB Pattern
Incomplete RBBB patterns can be produced by the following mechanisms
(1) different degrees of conduction delays through the main trunk of the right bundle branch (fig. 94-17)
(2) an increased conduction time through an elongated right bundle branch that is stretched because of a concomitant enlargement of the septal surface (as in congenital volume overload of the right ventricle)
(3) a diffuse Purkinje-myocardial delay due to right ventricular stretch or dilatation
(4) surgical trauma or disease-related interruption of the major ramifications of the right branch ("distal" RBBB or "right fascicular blocks") or
(5) congenital variations of the distribution of the major ramifications resulting in a slight delay in the activation of the crista supraventricularis.
Reference:Castellanos,A. and others,Hurst's The Heart 8th Edition,The Resting Electrocardiogram,321-356.
A conduction delay in the main trunk of the right bundle or in its major ramifications may be concealed (not manifested in the surface ECG) when there are coexisting (and of greater degree) conduction disturbances in the main left bundle branch, the anterosuperior division of the left bundle branch and/or the free left ventricular wall.
A RBBB can also be concealed in some patients with Wolff-Parkinson-White syndrome if the ventricular insertion of the accessory pathway causes preexcitation of the right ventricular regions that would be activated late because of the RBBB.
Reference:Castellanos,A. and others,Hurst's The Heart 8th Edition,The Resting Electrocardiogram,321-356.
This conduction disturbance is characterized by wide (greater than 0.11s) QRS complexes. The diagnostic criteria consist of prolongation of the QRS complexes (over 0.11s) with neither a q wave nor an S wave in lead V1 and in the "properly placed" V6. A wide R wave with a notch on its top ("plateau") is seen in these leads. In hearts with an electrical (and anatomic) vertical position a small Q wave may be seen in AVL in the absence of MI. Right chest lead V1 may or may not show an initial r wave, but the latter should be present in lead V2. Unfortunately, as mentioned in reference to complete RBBB, a complete LBBB form can be recorded in patients with high degree (not necessarily complete) LBBB. The direction of the electrical axis in patients showing QRS changes typical of complete LBBB has also been widely discussed.
In the majority of the human hearts, the site of exit from the right bundle branch does not seem to be at the lowermost right ventricular region (that called in pacemaker nomenclature the right ventricular apex). If this were the case, all complete LBBBs would show (as when the right ventricular apex is paced) abnormal left axis deviation whereas the electrical axis in "uncomplicated" complete LBBB block usually is not located beyond -30 degrees.
Reference: Castellanos, A. and others, Hurst's The Heart 8th Edition, The Resting Electrocardiogram,321-356.
Complete LBBB with MI
Normally, in complete LBBB, the impulse emerges from the right bundle branch and propagates to the left and slightly anteriorly. This orientation of the initial forces tend to abolish previously present inferiorly and laterally located abnormal Q waves characteristic of inferior and lateral MI. If the infarction is anteroseptal, however, the impulse cannot propagate toward the left. Instead, the initial vectors point toward the free wall of the right ventricle because now the right ventricular free-wall forces are not neutralized by the normally preponderant septal and/or initial left ventricular free Thus, a -wall forces. Thus, a small q wave will be recorded in leads (1, V5, and V6) where it is not normally recorded in complete LBBB (Fig. 94-18).
The most sensitive sign to detect acute MI is ST-segment elevation in leads facing the affected region (Fig. 94-19).
Reference: Castellanos,A. and others, Hurst's The Heart 8th Edition, The Resting Electrocardiogram,321-356.
Incomplete LBBB Pattern
An incomplete LBBB pattern can be diagnosed in a heart with an electrically horizontal (or semihorizontal) heart position when leads 1 and V6 show an R wave with a slurring in its upstroke ( not on its top, as incomplete LBBB). Lead V1 shows Rs or QS complexes, and lead V2 shows Rs complexes. Although QRS duration usually ranges between 0.o8 and 0.11s , this pattern can be observed with QRS durations of 0.12 and 0.13s.
Not surprisingly, an incomplete LBBB pattern can be produced by various processes, including the following
(1) conduction delays in the main trunk of the left bundle branch,
(2) conduction delays (of more or less equal degree) in the fascicles of the left bundle branch,
(3) diffuse septal fibrosis,
(4) small septal infarcts,
(5) left ventricular enlargements (generally due to pressure overloading) in patients with congenital heart disease, and
(6) combinations of all of the above.
Reference: Castellanos,A. and others, Hurst's The Heart 8th Edition, The Resting Electrocardiogram,321-356.
Wide QRS Complexes in Patients with Manifest Preexcitation Syndromes
The characteristic pattern of manifest Wolff-Parkinson-White syndrome consists of a short PR interval (reflecting faster than normal conduction through an accessory pathway of the Kent bundle type) preceding a wide QRS complex. The latter usually shows an initial slurring (delta wave) followed by a terminal, slender part. The classical ventricular complex is a fusion beat resulting from ventricular activation by two wave fronts. One, traversing the accessory pathway, produces the delta wave. The other, emerging from the normal pathway, is responsible for the terminal, more normal parts of the QRS complex.
The degree of preexcitation (amount of muscle activated through the accessory pathway) depends on many factors. Foremost among these are the distance between the sinus node and atrial insertion of accessory pathway and, more important, the differences in conduction time through the normal pathway and accessory pathway.
Other things being equal, a patient with rapid (enhanced) AV nodal conduction will have a smaller delta wave than a patient with slow conduction through the AV node. Moreover, if there is total block at the AV node or His-Purkinje system, the impulse will be conducted exclusively via the accessory pathway. When this occurs, the QRS complexes are no longer fusion beats, since the ventricles are then activated exclusively from the preexcited site. Consequently, the delta wave disappears and the QRS complexes are different than fusion beats, though the direction of the delta wave remains the same.
Moreover, the QRS complexes are as wide as (and really simulating) those produced by artificial or spontaneous beats arising in the vicinity of the ventricular end of the accessory pathway.
Also of importance are the characteristics of the QRS complexes of beats without preexcitation in relationship to the characteristics of beats resulting from exclusive accessory pathway conduction (which in turn depends on the location of the pathway). Not surprisingly, the EA can show marked changes when fusion beats are compared with pure peexcited beats (figure 94-20).
There are three major methods available for the anatomic localization of accessory pathways, namely intra operative mapping, catheter electrode techniques, analysis of the 12-lead ECG (least accurate but the easiest).
Left free-wall accessory pathways are characterized by negative or isoelectric delta waves in one of leads 1, AVL, V5 or V6. Lead V1 shows RS or R complexes (fig. 94-20). During sinus rhythm, the electrical axis may be normal, but when atrial fibrillation develops and elusive accessory pathway conduction occurs, the EA is deviated to the right and inferiorly (figure 94-20).
Posteroseptal accessory pathways show negative or ioselectric delta waves in two of LEADS 11, 111, or AVF and RS (or R) waves in V1,V2, or V3 (figure 94-21).
An Rs (or RS) wave in V1 suggests left paraseptal pathway a QS complex in the same lead may correspond to a right paraseptal pathway.
Right free-wall accessory pathways display an LBBB pattern defined, for purposes of accessory pathway localization, by an R wave greater than 0.09s in lead 1 and rS complexes in leads V1 and V2 with an EA ranging between+30 degrees to - 60 degrees (fig. 94-22).
The most rare right anteroseptal accessory pathways show an LBBB pattern with an EA between +30 degrees and +120 degrees (fig. 94-23). A q wave may be present in lead AVL but not in leads 1 orV6.
Mixed patterns may result from the existence of two separate accessory pathways.
Reference: Castellanos,A. and others, Hurst's The Heart 8th Edition, The Resting Electrocardiogram,321-356.
LEFT ATRIAL HYPERTROPHY
Clues to left atrial hypertrophy include (1) P-wave duration greater than 0.11 s and notched P wave with an interpeak interval in excess of 0.04 s and (2) negative phase of P in V1 longer than 0.04 s and greater than 1 mm in lead VI. These criteria apply to intraatrial block actually, and if found in patients with left ventricular enlargement or mitral stenosis, then left atrial hypertrophy is most likely present. The ECG pattern of left atrial hypertrophy results from a hypertrophy- induced intraatrial conduction delay.
LEFT VENTRICULAR HYPERTROPHY (LVH)
As emphasized by Surawicz, since the advent of other noninvasive techniques, there has been a changing role for the ECG in the diagnosis of ventricular hypertrophy. Necropsy studies have exposed the superiority of echocardiography with respect to electrocardiography to detect LV hypertrophy. Echocardiography is also a better method for the serial follow-up of changes during progression or regression of LV hypertrophy. Multiple criteria have been proposed to diagnose LV hypertrophy using necropsy or echocardiographic information (Table 3 and Table 4). Of these, the Sokolow-Lyon criterion (SV1 + RV5,6 _35 mm) is the most specific (>95 percent) but is not very sensitive (45 percent) (see Table 4). The Romhilt-Estes score has a specificity of 90 percent and a sensitivity of 60 percent in studies correlated with echocardiography. The following are some of the other criteria49: The Casale (modified Cornell) criterion (Ravl + SV, >28 mm in men and >20 in women) is somewhat more sensitive but less specific than the Sokolow-Lyon criterion. The Talbot criterion (R _16 mm in avL) is very specific (>90 percent), even in the presence of MI and ventricular block, but not very sensitive. The Koito and Spodick criterion (RV6> RV5) claims a specificity of 100 percent and a sensitivity of more than 50 percent. According to Hernandez Padial, a total 12-lead QRS voltage of greater than 120mm is a good ECG criterion of LV hypertrophy in systemic hypertension and is better than those most frequently used. With echocardiography as the "gold standard," several authors postulated ECG criteria for diagnosis of LV hypertrophy in the presence of complete LBBB and LAFB . The high sensitivity and specificity reported by Gertsch et al. for diagnosis of LV hypertrophy with LAFB have not been corroborated in preliminary studies performed in the department of A.Castellanos and others,Hurst,s THE HEART,10ty Edition,Chpt.11,p.302.
PROCESSES PRODUCING OR LEADING TO RVH AND ENLARGEMENT
Right ventricular hypertrophy is manifest in the ECG only when the right ventricular forces predominate over those of the left ventricle. Since the latter has, roughly, three times more mass than the former, the right ventricle may double in size (when the left ventricle is normal) or triple its weight (when there is significant LVH) and still not result in the necessary requirements to pull the electrical forces anteriorly and to the right. For these reasons, RVH cannot be recognized easily in adult patients.
The ECG manifestations of RVH or enlargement can be divided into the following three main types :
(1) the posterior and rightward displacement of QR forces associated with low voltage, as seen in patients with pulmonary emphysema (fig. 94-24)
(2) the incomplete RBBB pattern occurring in patients with chronic lung disease and some congenital cardiac malformation resulting in volume of the right ventricle (fig. 94-25)
(3) the true posterior wall myocardial infarction pattern with normal to low voltage of the R wave inV1 (fig. 94-26)
(4) and the classical right ventricular hypertrophy and strain pattern as seen in young patients with congenital heart disease (producing pressure overloading) or adult patients with high pressure ("primary " pulmonary hypertension) (fig. 94-27). False patterns of RVH may occur in patients with true posterior (basal) MI, complete RBBB with LPFB and Wolff-Parkinson- White syndrome resulting from AV conduction through the left free wall, or posteroseptal accessory pathways.
Because multiple factors can affect ventricular repolarization in diseased hearts, the finding characteristic of a specific electrolyte abnormality may be modified, and even mimicked, by various pathological processes and the effects of certain drugs. The major problem with the ECG diagnosis of electrolyte imbalance is not the negative ECG with abnormal serum values. But the production of similar changes by other conditions in patients with normal serum values.
The initial effect of acute hyperkalemia is the appearance of peaked T waves with a narrow base (Fig. 94-28a, left).The diagnosis of hyperkalemia is almost certain when the duration of the base is 0.20s or less (with rates between 60 and 110 per minute). As the degree of hyperkalemia increases, the QRS complex widens with the EA usually being deviated abnormally to the left, and rarely to the right (Fig. 94-28b). In addition, the PR interval prolongs, and the P wave flattens until it disappears (Fig. 94-28c).
The effect of hyperkalemia on cardiac rhythm is complex, and virtually any arrhythmia may be seen. Various bradyarrhythmias, including impaired AV conduction and complete AV block, may occur. If untreated, death ensues either due to ventricular standstill or coarse slow ventricular fibrillation.
Death can also result if wide QSR complexes (due to hyperkalemia) occurring at fast rates are diagnosed as ventricular tachycardia and the patient is treated with antiarrhythmic drugs.
In other circustances, tachycardias may result, including sinus tachycardia, frequent ventricular extrasystoles, ventricular tacycardia, and ventricular fibrillation.
The rate of K elevation appears to influence the type of arrhythmia produced. A slow elevation of K produces widespread block and depressed automaticity, and rapid infusions produce ventricular ectopic rhythms and terminally ventricular fibrillation.
Moderate hyperkalemia has been noted to suppress supraventricular and ventricular ectopic beats in about 80% of patients.
On the other hand, Class1A and ClassC drugs as well as large doses of tricyclic antidepressants (especially when ingested for suicide purposes) can also produce marked QRS widening. These processes, however, do not coexist with narrow-based, peaked T waves.
Myriad of clinical conditions have been described in association with T-wave inversion in the precordial leads. T-wave inversion associated with or without corrected QT prolongation may be encountered in a variety of clinical conditions.
In patients with T-wave inversion in the precordial leads, tailored diagnostic approach should be conducted avoiding overuse of diagnostic methods. Specific tailored diagnostic modalities and directed therapeutic interventions may be undertaken when high index of clinical suspicion is raised towards certain disease entity.
Innovations and breakthroughs
This study is a retrospective analysis of patients presented with T-wave inversion in the anterior chest leads. The T-wave inversion may be accompanied with or without QTc prolongation. Classification has been made into reversible and irreversible types to facilitate its differential diagnostic approach.
Awareness of the differential diagnosis of T-wave inversion in the precordial leads will help trainees and physicians to discern different entities and will prevent some patients from undergoing unnecessary invasive investigations and procedures.
In this paper, authors report the various clinical conditions of patients with T wave inversion in the anterior chest wall leads. This review article is interesting and very educational.
The second heart field (SHF) contains progenitors of all heart chambers, excluding the left ventricle. The SHF is patterned, and the anterior region is known to be destined to form the outflow tract and right ventricle.
The aim of this study was to map the fate of the posterior SHF (pSHF).
Methods and Results:
We examined the contribution of pSHF cells, labeled by lipophilic dye at the 4- to 6-somite stage, to regions of the heart at 20 to 25 somites, using mouse embryo culture. Cells more cranial in the pSHF contribute to the atrioventricular canal (AVC) and atria, whereas those more caudal generate the sinus venosus, but there is intermixing of fate throughout the pSHF. Caudal pSHF contributes symmetrically to the sinus venosus, but the fate of cranial pSHF is left/right asymmetrical. Left pSHF moves to dorsal left atrium and superior AVC, whereas right pSHF contributes to right atrium, ventral left atrium, and inferior AVC. Retrospective clonal analysis shows the relationships between AVC and atria to be clonal and that right and left progenitors diverge before first and second heart lineage separation. Cranial pSHF cells also contribute to the outflow tract: proximal and distal at 4 somites, and distal only at 6 somites. All outflow tract–destined cells are intermingled with those that will contribute to inflow and AVC.
These observations show asymmetric fate of the pSHF, resulting in unexpected left/right contributions to both poles of the heart and can be integrated into a model of the morphogenetic movement of cells during cardiac looping.
Cardiac precursor cells are located bilaterally as 2 symmetrical regions of the lateral plate splanchnic mesoderm at vertebrate primitive streak stages. 1,2 These cardiac precursors fuse at the ventral midline to form the cardiac crescent and subsequently the initial heart tube. 3 The classic view assumed that all cardiac progenitors reside in the heart tube, 4 but the idea that arterial pole cells may be added later, after looping, was suggested long ago 5 and has been definitively demonstrated in chick 6,7 and mouse. 8 It is now clear that, in all vertebrates, there is a population of cells, termed the second heart field (SHF), lying dorsal to the heart tube in pharyngeal mesoderm, which is a major source for all chambers of the heart, except the crescent-derived left ventricle. 9
The extent of the SHF in mouse has been defined by the strong expression of islet-1, and the contribution to the heart has been revealed using Islet1-Cre genetic tracing. 10,11 Retrospective clonal analyses have provided complementary linage data, revealing the early segregation of the first and second myocardial lineages, which correspond to the first heart field and SHF. Specific patterns of clones contributing to the looped heart tube have been identified, such as those colonizing both the inflow and outflow poles. 12,13 However, the embryological origin and genetic characteristics of the precursors have remained unknown. The boundaries of, and within, the heart-forming regions have been examined by a variety of approaches, 9,14 from which it appears that the anteroposterior (craniocaudal) axis of the SHF is patterned and varies in fate.
The anterior portion of the SHF (anterior heart field [AHF]) expresses Fgf8, Fgf10, and Tbx1, and genetic tracing using these genes, and an enhancer of Mef2c, shows that most of the right ventricle and all the outflow tract (OFT) myocardium are AHF-derived. 8,15,16 There is no equivalent expression marker of posterior SHF (pSHF), although podoplanin has been suggested, 17 but this is not specific for heart precursor cells. Controlling signals for the SHF include a Wnt2 pathway required for pSHF expansion 18 and a retinoic acid–mediated mechanism that restricts AHF growth. 19 Recently, it was shown that 3′ Hox a1 and b1 genes are regulated by retinoic acid and that these transcription factors act as effectors of SHF patterning. 20
Previously, using the Mlc1v-lacZ-24 transgenic reporter of Fgf10, we provided some evidence for an atrial fate of the Islet1+/Fgf10− pSHF cell population. 21 In this study, we have analyzed in detail the fate of small groups of pSHF cells using lipophilic dye labeling and mouse embryo culture to form a fate map of the Islet1+/Fgf10− subdomain. This shows that pSHF is a source of cells for both inflow and outflow cardiac regions, with left-right, craniocaudal, and stage-dependent patterns of contribution.
Outbred MF1 mice were used, except for the clonal analyses. The pSHF was defined by in situ hybridization for Islet1 and Mlc2a expression 10 and by X-gal staining of the Fgf10 transgenic reporter line, 8 Mlc1v-nLacZ-24. Cells within the Mlc2a−/Islet1+/Fgf10− pSHF region (4- and 6-somite stages Online Figures IH and II) or the most caudal Mlc2a−/Islet1+/Fgf10+ region (2 somites Online Figure IG) were labeled by injection of a lipophilic carbocyanine, DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), DiO (3,3'-dioctadecyloxacarbocyanine perchlorate) or DiR (1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide), as described previously. 22 Initial studies showed that injections label a contiguous group of 20 to 30 cells within the splanchnic mesoderm layer (see Online Data Supplement, Online Figure IVA–IVC).
Injected embryos were photographed immediately (t0), and the exact localization of dye was systematically recorded using a grid overlay (Online Figure VA–VD). Embryos were cultured for 40 hours (t40) in rolling bottles and then hearts were isolated, fixed, and dye distribution examined by confocal microscopy. The locations of label were charted onto systematically defined cardiac regions (Online Figure VE–VH), each of which is identified here by a color/symbol code (Online Figure VI) when related back to the site of injection.
Clonal analyses were made at E8.5 in embryos from the α-cardiac actin nlaacZ1.1/+ transgenic line that spontaneously generates random clones of β-galactosidase (β-gal)–positive myocardial cells, as previously described. 12,13 Statistical methods are given in the Online Data Supplement.
Establishing the Extent of pSHF With Molecular Markers
By definition, we consider the pSHF as that part of the Islet1-expressing SHF that does not express AHF markers, such as Fgf10. 21 We charted this domain precisely in embryos of 2 to 6 somites, using Islet1, Fgf10 (Mlc1v-nLacZ-24), and Mlc2a (myocardial marker for crescent) expression (Online Figures IB, IC, IE, IF, IH, and II). At 2 somites, even the most caudal region of the Islet1-expressing domain also showed Mlc1v-nLacZ-24 staining (Online Figure IA, ID, and IG), so no clear pSHF can be defined at this stage using these techniques.
PSHF Cells Contribute to the Venous Pole of the Heart With Craniocaudal, Left-Right, and Stage-Dependent Patterns
Previously, we showed that pSHF contributes to the ipsilateral atrium. 21 Here, we find that the left pSHF at 4 to 6 somites contributes to the dorsal wall of the left (common) atrium (LA), whereas the right pSHF contributes to both the dorsal and ventral regions of the right (common) atrium (RA Figure 1A–1D). Interestingly, the right pSHF also contributes contralaterally to the ventral side of the LA (Figure 1C–1G). Observation of labeled cells in the ventral LA after left pSHF injection was rare (2 cases, ≈2% injections Figure 1C–1G for details).
Figure 1. Contribution of the posterior second heart field (pSHF) to the dorsal atria and sinus venosus. A, An example of double-dye labeling of the right (arrow) and left (arrowhead) sides at 6 somites (brightfield/fluorescence). B, Fluorescence image of a dorsal view of the heart from the embryo labeled in (A) after 40 hours of culture. The pSHF cell contribution is shown by labeling at the dorsal right (arrows) and left atrium (white arrowhead) and sinus venosus (black arrowhead). C and D, Locations of all injections performed at 4 and 6 somites that produced dye labeling in the atria. E–G, The parts of the inflow region arising from the pSHF shown by color/shape code (Online Figure VI). RSV indicates right sinus venosus DLA, dorsal side of the left atrium LSV, left sinus venosus VLA, ventral side of the left atrium LV, left ventricle DRA, dorsal side of the right atrium RV, right ventricle OFT, outflow tract HT, heart tube 20s, 4s, 6s, 20-, 4-, and 6-somite stage, respectively VRA, ventral side of the right atrium.
Considering the whole pSHF, about two thirds of all injections resulted in labeling of the atrium, and this proportion did not differ between the 4- and 6-somite stages (65% and 63% of injections, respectively Online Figure IIA). However, the cranial and caudal halves of the pSHF show clear spatial differences in contribution, again similarly at 4 and 6 somites. The caudal portion of the pSHF was less likely than the cranial to contribute to the atria (Figure 1C and 1D Online Figure IIIC and IIID). Furthermore, the caudal portion also contributes more distally to the atria and to the sinuatrial region (Figure 2A and 2B and Figure 3C and 3D), whereas more cranial injections yielded labeled cells in proximal portions of the atria, closer to the atrioventricular junction.
Figure 2. Contribution of the posterior second heart field (pSHF) to the ventral atria and sinus venosus. A, An example of double-dye labeling at cranial (arrowhead) and caudal (arrow) portions of the right pSHF at 6 somites. B, Whole-mount fluorescence image of the embryonic heart labeled in (A) after 40 hours of culture, showing labeling at the ventral (arrowheads) and dorsal right atrium (RA white arrow) and right sinus venosus (black arrow). These regions are illustrated in similar view in Figure 1F. C, Left lateral view displaying ventral right and left common atria labeling (arrow and arrowhead, respectively see Figure 1F and 1G for schemes of B and C views). D and E, Locations of all injections at 4 and 6 somites, which produced labeling in the sinus venosus (Online Figure VI for scheme). F, Dorsal view after dye injection in the left pSHF showing labeling in the left sinus venosus (SV) and dorsal left atrium (LA) myocardium (myo). G, Transection of this heart (line in F) shows dye in the endocardium (endo arrow) as well as in the myo. HT indicates heart tube 20s, 4s, 6s, 20-, 4-, and 6-somite stage, respectively OFT, outflow tract DRA, dorsal side of the right atrium VRA, ventral side of the right atrium LV, left ventricle RV, right ventricle AVC, atrioventricular canal DLA, dorsal side of the left atrium.
Figure 3. Contribution of the posterior second heart field (pSHF) to the atrioventricular canal (AVC). Ventral view of a double-dye labeling (arrow and arrowhead) into the right (A) and left (C) pSHF at 4 somites. Cells from the right pSHF move to the inferior AVC (B, arrowhead), whereas the left pSHF contributes to the superior AVC (D, arrow and arrowhead). E and F, Locations of all injections at 4 and 6 somites that produced labeled cells in the AVC. CC indicates cardiac crescent 20s, 4s, 6s, 20-, 4-, and 6-somite stage, respectively LV, left ventricle DLA, dorsal side of the left atrium HT, heart tube AVC, atrioventricular canal IAVC, inferior atrioventricular canal VLA, ventral side of the left atrium LV, left ventricle DLA, dorsal side of the left atrium LSV, left sinus venosus.
There seems to be a difference in the allocation process between the dorsal and ventral RA. Of all injections that labeled the RA, 46% contributed to the dorsal portion only, 51% to dorsal and ventral, and 3% to ventral only. So, 97% of the ventral label also displayed dorsal label, which could be accounted for by cells contributing first dorsally, then a subpopulation moving ventrally. In support of this, contiguous regions of labeled cells were observed in the lateral dorsal region through the right lateral wall and into the ventral portion (Figure 2A–2C).
The right cells that contribute contralaterally to the ventral LA lie in the cranial region of the pSHF: 10% cranial injections compared with 2% caudal. Furthermore, the vast majority (81%) of injections that resulted in contralateral contribution also resulted in ipsilateral labeling in the ventral and dorsal side RA. Again, this may reflect a progressive contribution from the cranial right pSHF to dorsal right, ventral right, and then ventral left regions of the atrium.
Injections in the pSHF also produced labeled cells in the sinus venosus region, which we define at this stage as that region caudal to the visible sulcus at the atrium–body wall junction (Figures 1A, 1B, 2A, 2B, 2D, and 2E). Of all cases of sinus venosus contribution, 70% showed contribution to the atrium also, with a contiguous region of labeled cells. However, in contrast to the observations in the atria, contralateral labeling from one side of the pSHF to the other sinus venosus was very rare (1 and 2 cases from left and right [L&R], respectively). The overall area occupied by sinus venosus precursors in the pSHF is somewhat greater than that for the atria, extending more caudally and medially (Figure 2D and 2E and Online Figure IIIC and IIID). In accordance with observations in the atria, sinus venous–destined cells were more likely to reside in the caudal half of the pSHF at the 4-somite stage (Figure 2D and 2E and Online Figure IIC). However, contrary to the atria, there was a clear stage difference between the 4- and 6-somite stages, with consistently more sinus venosus contribution at the older stage (Online Figure IIC). This indicates that sinus venosus precursors are added to the domain of Isl1 expression between the 4- and 6-somite stages.
We did not systematically analyze contribution to the endocardium (indeed all observations described here refer to myocardium), but sectioning of hearts shows that, in the inflow region, labeled cells are found in both endocardium and myocardium (Figure 2F and 2G). This is consistent with analyses of Islet1-cre mice, suggesting a common origin from Islet1-expressing precursors for these 2 cell types. 10
Left and Right pSHFs Contribute Differently to the AVC Region
Overall, 14% of pSHF injections at 4- and 6-somite stages showed labeled cells in the atrioventricular canal (AVC) region, of which the vast majority (97%) also showed atrial contribution. Strikingly, the contributions to the AVC from the left and right pSHFs were markedly different. Consistently, labeled cells from the right pSHF contributed to the inferior AVC (Figure 3A, 3B, and 3E–3G), whereas cells from the left pSHF contributed to the superior and left lateral AVC (hereafter superior AVC), corresponding with the outer curvature of the AVC (Figure 3C, 3D, and 3E–3G). Curiously, no labeled cells from the pSHF were observed in the right lateral side of the AVC, corresponding with the inner curve, closer to the OFT region. Furthermore, there were no cases of an individual injection resulting in labeling of both the inferior and the superior AVC.
Although the AVC-destined region of the pSHF overlapped with the atria/sinus venosus precursors (Online Figure IIIE and IIIF), AVC-contributing cells were localized almost exclusively in the most cranial portion of the pSHF (Figure 3E–3G and Online Figure IID). In contrast to the sinus venosus, the proportion of injections that resulted in AVC-labeled cells decreased between 4 and 6 somites (Online Figure IIA). This indicates that AVC precursor cells have left the SHF by the 6-somite stage and have been fully recruited to the heart tube.
There is a close relationship between contributions to regions of the atria and regions of the AVC. Thus, in 100% of cases showing labeled cells in the superior AVC region, there were also labeled cells in the dorsal LA. Conversely, 88% of inferior AVC-labeled hearts also showed contribution to the ventral LA. There were no examples of superior AVC plus ventral LA nor of inferior AVC plus dorsal LA patterns of labeling in this study. L&R pSHF contributions to atria and AVC are summarized in Figure 7B and 7C.
We aimed to gain insight into the clonal relationships between the inferior and superior AVC, as well as between the AVC and inflow regions. To investigate these relationships by a complementary approach, we studied α-cardiac actinnlaacZ1.1/+ E8.5 embryos, which allows retrospective clonal analysis of myocardial cells in the mouse heart. 12 Thus, from a collection of 4967 α-cardiac actinnlaacZ1.1/+ embryos of 8 to 21 somites, we selected all those that had β-gal–positive groups of cells in the AVC or atria (Online Table I). Among these 96 embryos, 33% showed β-gal–positive cells in the superior AVC (Figure 4C, 4F, and 4H), whereas only 10% displayed positive cells in the inferior AVC (Figure 4E, 4G, and 4I). This difference, in a random collection of clones, probably reflects the difference in size, and therefore numbers of progenitor cells, between these 2 regions, the superior AVC being larger. The exclusive participation in either region of the AVC in most embryos suggests that these 2 regions have different clonal origins and that up to the stage of 21 somites there is no intermixing of these populations. We observed only 2 embryos (Figure 4A and 4B), with β-gal expressing cells that occupied both the inferior and the superior AVC. Statistical analysis (Online Table I) suggests that these clones arise from common precursors of the 2 AVC regions. Indeed, the clone in Figure 4A, which contains 1370 β-gal–positive cells colonizing all regions of the heart, is the biggest clone of the collection, indicative of a very early event of recombination. The other clone colonizing both AVC regions (Figure 4B) contains 42 β-gal–positive cells in the right and left ventricles and the AVC. It has been classified as a large clone of the first myocardial lineage. 13 However, most large clones of the first (n=13) or second (n=13) myocardial lineage, as well as very large clones arising from common precursors of the first and second myocardial lineages (n=4 Figure 4C and 4E), have an exclusive contribution to either the superolateral or the inferior AVC. This means that the segregation between the 2 AVC regions precedes the segregation of the 2 lineages (Figure 4D).
Figure 4. Clonal relationships between the atria and the atrioventricular canal. Examples of E8.5 α-cardiac actinnlaacZ1.1/+ embryos displaying β-galactosidase–positive cells in the inferior (red arrowhead) or superior (lilac arrowhead) atrioventricular canal (AVC), the ventral right atrium (red chevron), or the ventral (red arrow) or dorsal (lilac arrow) left atrium. A and B, Two clones participate in both AVC regions. C and E, Examples of clones from common progenitors of the first and second myocardial lineage (demonstrated by labeling in both the outflow tract [OFT] and left ventricle), with a restricted contribution to 1 AVC region. F and G, Examples of clones restricted to 1 AVC region, arising from a precursor of either the first lineage (G) contributing to the left ventricle or the second lineage (F) contributing to the OFT. H and I, Examples of more recent clones restricted to 1 AVC region. Letter/numbers in each panel indicate the identification code of the clone number with s is somite stage. D, Reconstruction of the lineage tree of myocardial precursors, showing that the left/right regionalization of the heart field, which will give rise to the superior/inferior AVC, respectively, precedes the segregation between the first/second myocardial lineages. Letters in brackets refer to the panels showing an example of such precursor (the color code lilac=of left origin and red=of right origin is also used in Figure 7 and is different from the scheme used in other Figures). LV indicates left ventricle 10s, 11s, 21s, 10-, 11-, and 21-somite stage, respectively LA, left atrium RA, right atrium AVC, atrioventricular canal OFT, outflow tract SAVC, superior atrioventricular canal VLA, ventral side of the left atrium IAVC, inferior atrioventricular canal.
β-gal–positive labeling restricted to a region of the AVC was frequently associated with positive cells in the atria (80%). The majority (63%) of embryonic hearts with LacZ-labeled cells in the superior AVC only also showed β-gal–positive cells in the dorsal LA (Figure 4H), and less frequently (20%) in the ventral LA (Figure 4C). There was a single example of LacZ labeling on both the superior AVC and right atrium. Statistical analysis confirms the clonal relationship between the superior AVC and the LA, but not with the RA. In contrast, all hearts that showed β-gal–positive cells in the inferior-only AVC also contained LacZ-labeled cells in the ventral LA or the RA or both (Figure 4E, 4G, and 4I). Statistical analysis indicates that the inferior AVC is clonally related to the ventral LA and the RA, but not to the dorsal LA (Online Table II).
Taken together, these results suggest that the inferior and superior regions of the AVC have different origins, and the inferior part is clonally related to the ventral portion of the atria, whereas the superior portion is clonally related to the LA (Figure 4D). This is wholly consistent with our dye labeling data, and given our conclusion that left pSHF contributes to the dorsal wall of the LA, we conclude that the bulk of AVC (the superolateral portion) is also of left pSHF origin.
PSHF Cells Colonize the Arterial Pole of the Heart
Interestingly, labeling of the most cranial portions of the pSHF in embryos from 4 to 6 somites resulted in labeled cells at the arterial pole of the developing heart (Figure 5). At the 25-somite stage examined, our data show an ipsilateral cell contribution from the pSHF to the OFT (summarized in Figure 7D). We found OFT precursor cells in an extensive area of the pSHF, overlapping with those obtained for the inflow tract (IFT)/AVC cardiac regions (Figure 5H–5J and Online Figure IIIG and IIIH). Almost all OFT-labeled embryos also presented staining of the IFT (94%), suggesting that IFT- and OFT-derived cells may share a common precursor pool in the pSHF and the pSHF may be composed of an intermingling of IFT-destined plus OFT-destined cells.
Figure 5. Contribution of the posterior second heart field (pSHF) to the outflow tract (OFT). Dye labeling (arrows) into the left pSHF at 4 somites (A) and into the right pSHF at 6 somites (B). C and D, Dorsal views of hearts from the embryos labeled in A and B, respectively, showing labeled cells in the distal OFT on the left (C, arrows) and right (D, arrow) sides. Note that the injections performed in A and B produced labeled cells in the inflow tract region (arrowheads) also. H and I, Locations of all the injections at 4 and 6 somites that produced labeling of the OFT. J, Regions of the outflow region derived from the pSHF. CC indicates cardiac crescent HT, heart tube OFT, outflow tract DLA, dorsal side of the left atrium DRA, dorsal side of the right atrium LV, left ventricle RV, right ventricle 6s, 18s, 4s, 6-, 18-, and 4-somite stage, respectively.
As previously described for IFT and AVC-destined cells, OFT precursor cells followed a craniocaudal pattern of contribution, that is, the OFT contribution was higher in the cranial portions of the pSHF (Figure 5H–5J Online Figure IIE). In addition, at 4 somites, labeled cells contributed to both distal (aortic sac/OFT boundary) and proximal (OFT/right ventricle boundary) portions of the arterial pole, whereas only distal contribution to the OFT was observed at 6 somites (Figure 5H–5J). This suggests a sequential process of pSHF recruitment to the OFT (Figure 5H–5J Online Figure IIE).
PSHF Supplies Fgf10-Expressing and Nonexpressing Cells to the OFT
Previous studies, including those using the Mlc1v-nLacZ-24 reporter, have demonstrated that much of the OFT is derived from Fgf10-expressing cells. 8 Our results, showing a contribution of the Fgf10-negative pSHF to the OFT, led us to ask whether or not these cells switch on Fgf10 when contributing to the arterial pole. Sections of OFT from Mlc1v-nLacZ-24 embryos show a mix of β-gal–positive and β-gal–negative cells (Figure 6A–6D). We dye-injected the pSHF of Mlc1v-nLacZ-24 embryos producing dye labeling of the dorsal pericardial wall at t40, overlapping with the β-gal domain of Mlc1v-nLacZ-24 staining (Figure 6E–6F). Isolation of this region and further examination demonstrated that the dye was localized in β-gal–negative and β-gal–positive cells (Figure 6G–6I). However, we cannot estimate what fraction of all OFT contributing pSHF cells do not express Fgf10. Also, we cannot rule out the possibility that there is slow or incomplete activation of the Mlc1v-nLacZ-24 transgene in this population.
Figure 6. The posterior second heart field (pSHF) contribution to the outflow tract (OFT) is a mix of Fgf10-expressing and nonexpressing cells. A–D, Sections of the distal OFT (superior to the top, right side on the left) from an Mlc1v-nLacZ-24/Fgf10 reporter embryo at 20 somites showing: (A) β-galactosidase (β-gal) (B) immunohistochemistry for cardiac troponin I (C) nuclei by propidium iodine (D) and all 3 merged. Note that not all myocardial cells are β-gal–positive (eg compare A and B arrow and arrowhead denote β-gal–positive and β-gal–negative cells, respectively). E, An Mlc1v-nLacZ-24 embryo at 6 somites after injection of dye into the right pSHF (arrow). After 40 hours of culture and β-gal staining (F), dye labeling (blue) is dorsal to the heart and overlapping (arrows) with the expression of the Mlc1v-nLacZ-24 (black) in the dorsal mesocardium. Explants from this dorsal mesocardium show partial colocalization of the dye and reporter gene expression (G–I). G, Fluorescence image of dye, (H) nonfluorescence image showing Mlc1v-nLacZ-24 positive and negative cells, and (I) merge of G and H.
The Posterior-Most SHF at 2 Somites Is Predominantly of OFT Fate
We find that the posterior-most portion of Islet1+ splanchnic mesoderm at 2 somites also expresses Fgf10, showing that there is no pSHF, by our molecular definition, at this stage. Nevertheless, we labeled the posterior-most Islet1+ region of 2 somite embryos and found that 95% contributed to the OFT with only 48% showing IFT labeling (n=10 Online Figure IIF). This contrasts with the pSHF at 4 and 6 somites, which is mainly destined to form the inflow region. At 2 somites, inflow progenitors lie slightly more medial than outflow progenitors (Figure 7A). The contribution to the inflow cardiac regions displayed, overall, similar left-right and craniocaudal patterns to those observed at 4 to 6 somites (data not shown). These observations suggest that from the 2-somite stage there is recruitment of cells to the pSHF, with progressive anterior-ward movement of cells within the SHF.
Figure 7. A, At 2 somites, outflow precursors are located more medially in second heart field (SHF) than inflow progenitors, although there is extensive overlapping. B to D, A summary of the contributions to the heart from the right (red) and left (lilac) posterior SHF (pSHF). E, A model of the movement of pSHF cells into the heart during the morphogenetic processes of looping (ventral and dorsal views hearts artificially stretched out, inflow to outflow color scheme as in Online Figure V). Cells from the left pSHF move to populate the left sinus venosus (light brown), dorsal left atrium (light green), and superior/medial atrioventricular canal (light yellow). In contrast, more cranial right pSHF cells move to the ventral (dark blue) right atrium (dark blue), ventral left common atrium (light blue), and inferior portions of the atrioventricular canal (dark yellow). Cells more caudally within the right pSHF contribute to the dorsal right atrium (dark green) and right sinus venosus (dark brown). RV indicates right ventricle RA, right atrium LV, left ventricle 2s, 20s, 4s, 6s, 8s, 10s, 2-, 20-, 4-, 6-, 8-, and 10-somite stage, respectively OFT, outflow tract IFT, inflow tract DLA, dorsal side of the left atrium SAVC, superior atrioventricular canal IAVC, inferior atrioventricular canal.
Craniocaudal Patterning of the pSHF
Several lines of evidence have shown that the fate of cells from the SHF in the mouse varies according to the anteroposterior (craniocaudal) position within this region. An anterior domain is marked by the expression of genes, including Fgf8, Fgf10, Tbx1, and an Mef2c enhancer, and forms the OFT and right ventricle. 8,10,15,16 A posterior domain contributes to the atrial chambers. 10,21 We now show that there is further craniocaudal patterning within the pSHF domain, although without sharp boundaries.
The most cranial pSHF contributes to the atrioventricular canal, the most caudal part contributes to the sinus venosus, and atrial progenitors lie predominantly in between. This suggests that cells within the pSHF add sequentially to the heart tube, with anteroposterior position predicting regional contribution to the heart, from outflow to inflow. Little is known of the molecular mechanisms that may encode craniocaudal identity within the pSHF. Retinoic acid signaling limits the extent of the SHF, 19 and recently it has been shown to be required for the correct deployment of Hox-expressing SHF cells. 20 Furthermore, regionalized expression of Hoxb1 and Hoxa1 seems to be required for anteroposterior patterning of the SHF. 20
Importantly, at the stages examined here, the cranial pSHF contributes asymmetrically to the left and right sides of the heart, whereas derivatives from the caudal pSHF contribute symmetrically. We have looked at pSHF contributions to the heart at the 20- to 25-somite stage, and the region we have identified as the sinus venosus will develop further into inflow regions of the atria, the coronary sinus, and proximal parts of the caval veins, so it is possible that some asymmetric contributions might be revealed at later stages. However, a companion article 23 to this demonstrates clonal relationships between the LA and the left superior caval vein, and between the RA and the right superior caval vein at E14.5, thus strongly supporting the progressive ipsilateral development that we have observed from the pSHF to the future atria and systemic veins.
The sequential craniocaudal arrangement of precursors within the mouse pSHF is stage-dependent and is overlapped by progenitors of the arterial pole (see below). In apparent contrast, in the chick the medial and lateral cardiogenic mesoderm contribute to the most cranial and caudal portions of the heart, respectively. 24 We see no evidence of mediolateral patterning at 4 to 6 somites in the mouse, but this is probably explained by the earlier stage examined in the chick before splanchnic mesoderm rotation. 25 At 2 somites, we do observe a more medial and lateral disposition of outflow and IFT progenitor cells, respectively, comparable with the arrangement in the chick heart-forming regions. 24
PSHF Also Contributes to the Arterial Pole
We find a robust contribution of the more cranial part of the pSHF to the arterial pole, as well as to the inflow regions. This may seem surprising, given that genetic tracing studies suggested that the OFT is entirely derived from the AHF. 8,10,15,16 However, some previous studies in the chick 26 and recent genetic tracing and clonal studies in the mouse support this notion. Cre tracing shows that pSHF cells that have expressed Hoxb1, Hoxa1, and Hoxa3 contribute not only to the inflow but also to the arterial pole, specifically to the OFT myocardium of the pulmonary trunk. 20 In addition, clonal analysis in the E8.5 heart 13 and E14.5 heart 23 shows a clonal relationship between the atria and the OFT myocardium.
From our current studies, we are not able to relate left and right pSHF progenitors to the pulmonary or aortic parts of the OFT. At the 20- to 25-somite stage at which we assessed contribution, the left pSHF contributed to the left side of the OFT and the right side similarly. However, we and others have shown a functional rotation of the OFT at later stages of development, which moves cells from the left side to populate the subpulmonary myocardium, 27 and there is a clonal relationship between pulmonary myocardium and left head muscles derived from the SHF. 28 As is the case for the inflow, we found evidence for sequential addition of cells from the pSHF to the OFT, with progenitors labeled at 4 somites contributing proximally and at 6 somites distally. A similar sequential relationship is seen in descendants of Hoxb1-expressing cells, which populate the proximal OFT, and Hoxa1 and Hoxa3 descendants that appear more distally. 20
As discussed, there are clonal and genetic data that support the existence of SHF cells that are progenitors of both outflow and inflow myocardium. Because we labeled groups of cells, we cannot draw any conclusions about lineage relationships, but, nevertheless, it is very clear from our observations that adjacent pSHF cells contribute to both poles of the heart, which raises questions about their paths of movement and how they are allocated to one pole or the other. The majority of pSHF cells move into the atrioventricular canal, atria, and sinus venosus, which seems to be a contiguous route to the heart tube via the sinus horns. In contrast, those pSHF cells that contribute to the OFT are likely to move via the dorsal pericardial wall, which is the location of the AHF cells that form the majority of the OFT. This is compatible with the caudal movement of the outflow region of the heart, relative to the pharyngeal region, over this time period, and we have observed labeled cells in the dorsal pericardial wall at 20 somites after labeling of pSHF at 4 to 6 somites. It is possible that this pathway of migration is controlled by Tbx1. It has been shown that, in Tbx1 −/− mice, AHF cells marked by the Mlc1v-nLacZ-24 transgene are found ectopically in the dorsal RA, rather than in their normal location in the OFT. 29
If pSHF cells move to the OFT via the dorsal pericardial wall, which is populated by AHF cells, it may be expected that the originally pSHF cells switch on AHF molecular markers during their relocation. Again using the Mlc1v-nLacZ-24 transgene marker, we found that this is the case for some cells labeled in the pSHF, but apparently not all. It is possible that some cells switch on AHF markers slowly, so are not yet expressing at the 20- to 25-somite stage we assessed, or that the transgene is not fully reflecting endogenous Fgf10 expression or that Fgf10 does not mark all AHF cells. Alternatively, the OFT at this stage may be a molecular mosaic, which has not been previously reported.
Left-Right Asymmetric Contributions From the pSHF
We observed 2 marked left-right asymmetries in pSHF contributions, in relation to the atrioventricular canal and to regions of the atria. The left pSHF gives rise to the myocardium overlying the superior atrioventricular region, whereas the right pSHF contributed to the inferior region. Labeling much earlier, at the 4-cell stage, has shown this same left-sided origin of the superior AVC region in Xenopus 30 but has not been reported previously in mammals. Left-right asymmetries in heart development, excepting looping, are controlled by the left-sided expression of Pitx2c, which is known to pattern the SHF. 21 Pitx2 is strongly expressed in superior, but not inferior, atrioventricular myocardium. 31 Thus, Pitx2 is expressed in cells at the origin and destination of the movement from left pSHF to superior region of the atrioventricular canal, but it is not clear whether Pitx2 is required for this relocation. Pitx2c mutant hearts have AVC abnormalities, 32 but any relationship to movement of cells from the left pSHF is untested.
Although the pSHF predominantly contributes to the ipsilateral atria, as previously reported in mouse 21 and chick, 25 we found that the right pSHF contributes to a subportion of the left ventral atrium. It is not clear what region of the fully formed atrium is represented in the left ventral atrium at the 20- to 25-somite stage, but again there is a correlation with Pitx2 expression. Recent detailed analysis of Pitx2 expression, using a reporter transgene, shows that at E9.5 the ventral LA and inferior AVC are Pitx2-negative, whereas the dorsal region is positive, with a domain extending over the superior AVC. 31
Our clonal analyses show that the 2 lineages which give rise to left and right progenitor populations segregate from common precursors before the separation of the first and second heart lineages (Figure 4D). This is compatible with the common precursors being located in the primitive streak and the progenitor populations in the initial bilateral heart fields, each of which then contributes to the first and second heart lineages (fields). Thus, cells of the superior AVC are already allocated in the left heart field.
The cell movements we describe may be part of the tissue-level forces that drive early heart morphogenesis. The progressive movement of cells of the atrial/atrioventricular region from dorsal right to ventral left (Figure 7E and 7F) may be related to rightward looping, the initial leftward jog of the AVC, and the clockwise (viewed from the aortic sac) torsion of the heart tube. 33,34 It is possible that abnormality in this process could lead to congenital looping defects such as tetralogy of Fallot. That left pSHF cells do not move rightward, contributing instead to the superior AVC (Figure 7E and 7F), may explain the expansion of this region, relative to the inferior AVC. Human laterality syndromes include a wide range of congenital heart defects, including the atrioventricular connections such as double outlet right ventricle, which may be explained by defects in the left-right asymmetrical contributions of the pSHF.
We thank E. Pecnard for his participation in collecting α-cardiac actin nlaacZ1.1/+ embryos and J-F. Le Garrec for help with the statistical analyses. S.M.M. is an INSERM research scientist.
Sources of Funding
This work was supported by the European Community’s Sixth Framework Programme contract (Heart Repair) SHM-CT-2005–018630 and by a British Heart Foundation Programme grant RG/03/012 .
- P wave: the sequential activation (depolarization) of the right and left atria
- QRS complex: right and left ventricular depolarization (normally the ventricles are activated simultaneously)
- ST-T wave: ventricular repolarization
- U wave: origin for this wave is not clear - but probably represents "afterdepolarizations" in the ventricles
- PR interval: time interval from onset of atrial depolarization (P wave) to onset of ventricular depolarization (QRS complex)
- QRS duration: duration of ventricular muscle depolarization
- QT interval: duration of ventricular depolarization and repolarization
- RR interval: duration of ventricular cardiac cycle (an indicator of ventricular rate)
- PP interval: duration of atrial cycle (an indicator of atrial rate)
It is important to remember that the 12-lead ECG provides spatial information about the heart's electrical activity in 3 approximately orthogonal directions:
Each of the 12 leads represents a particular orientation in space, as indicated below (RA = right arm LA = left arm, LL = left foot):
Heart function assessed by measuring left ventricular volumes.
In patients with valvular insufficiency or ischemic heart disease, the enlargement of the left ventricular volume (particularly end-systolic LVESV) can be related to a poor prognosis. For this reason, serial measurements of left ventricular size and function are used to follow these patients so that surgical intervention can be performed prior to irreversible damage to the heart is done. Similarly, patients recovering from a large myocardial infarction can develop adverse left ventricular remodeling leading to irreversible damage and the development of clinical heart failure. Below is an MRI study of a patient who sustained a large anterior myocardial infarction. At baseline (upper image), the left ventricular end-diastolic volume (LVEDV) measured 250 ml, the end systolic volume (LVESV) 173 ml with reduced heart function and ejection fraction (EF) 30%. One year later, another MRI study (lower image) was performed on the same patient and revealed an enlargement of left ventricular size with LVEDV of 314 ml, LVESV of 241 ml and a weakening of the heart function and ejection fraction EF of 23%. This is called adverse remodeling and has a poorer prognosis in patients after a myocardial infarction.
The atria and ventricles work together, alternately contracting and relaxing to pump blood through your heart. The electrical system of your heart is the power source that makes this possible.
Your heartbeat is triggered by electrical impulses that travel down a special pathway through your heart:
- SA node (sinoatrial node) – known as the heart’s natural pacemaker. The impulse starts in a small bundle of specialized cells located in the right atrium, called the SA node. The electrical activity spreads through the walls of the atria and causes them to contract. This forces blood into the ventricles. The SA node sets the rate and rhythm of your heartbeat. Normal heart rhythm is often called normal sinus rhythm because the SA (sinus) node fires regularly.
- AV node (atrioventricular node). The AV node is a cluster of cells in the center of the heart between the atria and ventricles, and acts like a gate that slows the electrical signal before it enters the ventricles. This delay gives the atria time to contract before the ventricles do.
- His-Purkinje Network. This pathway of fibers sends the impulse to the muscular walls of the ventricles and causes them to contract. This forces blood out of the heart to the lungs and body.
- The SA node fires another impulse and the cycle begins again.
At rest, a normal heart beats around 50 to 99 times a minute. Exercise, emotions, fever and some medications can cause your heart to beat faster, sometimes to well over 100 beats per minute.
How fast does the normal heart beat?
How fast the heart beats depends on the body's need for oxygen-rich blood. At rest, the SA node causes your heart to beat about 50 to 100 times each minute. During activity or excitement, your body needs more oxygen-rich blood the heart rate rises to well over 100 beats per minute.
Medications and some medical conditions may affect how fast your heart-rate is at rest and with exercise.
How do you know how fast your heart is beating?
You can tell how fast your heart is beating (your heart rate) by feeling your pulse. Your heart-rate is the amount of times your heart beats in one minute.
You will need a watch with a second hand.
Place your index and middle finger of your hand on the inner wrist of the other arm, just below the base of the thumb.
You should feel a tapping or pulsing against your fingers.
Count the number of taps you feel in 10 seconds.
Multiply that number by 6 to find out your heart-rate for one minute:
Pulse in 10 seconds x 6 = __ beats per minute (your heart-rate)
When feeling your pulse, you can also tell if your heart rhythm is regular or not.
Normal Heart Beat
1. The SA node sets the rate and rhythm of your heartbeat.
2. The SA node fires an impulse. The impulse spreads through the walls of the right and left atria, causing them to contract. This forces blood into the ventricles.
3. The impulse travels to the AV node. Here, the impulse slows for a moment before going on to the ventricles.
4. The impulse travels through a pathway of fibers called the HIS-Purkinje network. This network sends the impulse into the ventricles and causes them to contract. This forces blood out of the heart to the lungs and body.
5. The SA node fires another impulse. The cycle begins again.