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Europace Advance Access originally published online on December 13, 2008
Europace 2009 11(2):169-177; doi:10.1093/europace/eun335
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Electrophysiology and Ablation

Non-invasive detection of conduction pathways to left atrium using magnetocardiography: validation by intra-cardiac electroanatomic mapping

Raija Jurkko1,2,*, Ville Mäntynen2,3, Jari M. Tapanainen1,2, Juha Montonen2, Heikki Väänänen3, Hannu Parikka1,2 and Lauri Toivonen1,2

1 Department of Cardiology Helsinki University Central Hospital, FI-00290 Helsinki, Finland; 2 BioMag Laboratory HUSLAB, Helsinki University Central Hospital, Helsinki, Finland; 3 Laboratory of Biomedical Engineering, Helsinki University of Technology, Espoo, Finland

Manuscript submitted 13 September 2008. Accepted after revision 11 November 2008.

* Corresponding author. Tel: +358 9 4717 2442, Fax: +358 9 4717 4574, Email: raija.jurkko{at}2me.fi


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusions
 Funding
 Appendix
 References
 
Aims: Alteration in conduction from right to left atrium (LA) is linked to susceptibility to atrial fibrillation (AF). We examined whether different inter-atrial conduction pathways can be identified non-invasively by magnetocardiographic mapping (MCG).

Methods and results: In 27 patients undergoing catheter ablation of paroxysmal AF, LA activation sequence was determined during sinus rhythm using invasive electroanatomic mapping. Before this, 99-channel magnetocardiography was recorded over anterior chest. The orientation of the magnetic fields during the early (40–70 ms from P onset) and later part (last 50%) of LA depolarization was determined using pseudocurrent conversion. Breakthrough of electrical activation to LA occurred through Bachmann bundle (BB) in 14, margin of fossa ovalis (FO) in 3, coronary sinus ostial region (CS) in 2, and their combinations in 10 cases by invasive reference in total of 29 different P-waves. Based on the combination of pseudocurrent angles over early and late parts of LA activation, the MCG maps were divided to three types. These types correctly identified the LA breakthrough sites to BB, CS, FO, or their combinations in 27 of 29 (93%) cases.

Conclusion: Magnetocardiographic mapping seems capable of distinguishing inter-atrial conduction pathways. Recognizing the inter-atrial conduction pattern may assist in understanding the pathogenesis of AF and identifying the subgroups for patient-tailored therapy.

Key Words: Atrial fibrillation, Inter-atrial conduction, Electroanatomic mapping, Magnetocardiography


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusions
 Funding
 Appendix
 References
 
Conduction disturbances in the atria have a role in the genesis and maintenance of atrial fibrillation (AF).1Go,2Go In the intact human heart, the conduction from the right atrium (RA) to the left atrium (LA) is known to occur through Bachmann bundle (BB), the rim of fossa ovalis (FO), and the coronary sinus ostial region (CS).3Go–9Go The RA activation is oriented mainly from the right of the subject to leftward down.4Go,6Go,10Go,11Go Similar descending activation pattern has been demonstrated in the LA. However, signal propagation in LA can be also ascending and has then been related to block in BB.11Go,12Go The signal breakthrough sites in LA are in accordance with anatomic muscle bundles;13Go–16Go the number, location, and thickness of which are largely variable. The anatomical bundles are known to be variable also in healthy subjects,14Go,16Go but the knowledge of inter-atrial conduction is derived mainly from patients with clinical arrhythmias. In order to investigate large populations, more applicable non-invasive methods are needed.

Some electrocardiographic features, such as P-wave prolongation and morphological changes in the end of the P-wave, have been proposed to represent inter-atrial conduction block and vulnerability to AF.12Go,17Go,18Go Recently, three vectorcardiographic atrial wave patterns were related to distinct inter-atrial conduction pathways.9Go Magnetocardiography (MCG) is a non-invasive method complementary to ECG to examine cardiac electromagnetic activity. Essential to electrical and magnetic fields is a 90° spatial angle between the fields.19Go In MCG, the currents tangential to Bz component, which is perpendicular to the sensor surface and anterior chest, yield the strongest signal whereas ECG is sensitive to radial currents. Magnetocardiography may therefore show deviation from normal direction of depolarization and repolarization differently compared with ECG.19Go Consequently, currents tangential to the chest surface, as most currents in the atrial walls are, might be better detectable by MCG than by ECG. Magnetocardiography is also less affected by conductivity variations caused by the lungs, muscles, and skin.19Go

Magnetocardiography has been accurate in detecting ventricular arrhythmia substrate and localizing cardiac electrical sources,20Go,21Go and can also be used to analyse the direction of cardiac activation sequences.22Go Preliminary results of MCG mapping of atrial signal propagation during sinus rhythm suggested more variation in atrial activation pattern between AF patients than healthy subjects.23Go Differences were seen mainly in the later parts of the atrial complex and were hypothesized to reflect variation in the propagation of LA activation due to differences in inter-atrial conduction. To test this hypothesis, we examined the relationship between atrial activation patterns derived from MCG mapping and invasive electroanatomic activation maps.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusions
 Funding
 Appendix
 References
 
Study population
The study included 27 patients undergoing electrophysiological study prior to catheter ablation therapy of paroxysmal AF. The presence of structural heart disease was assessed by clinical, ECG, and cardiac ultrasound examinations. Anti-arrhythmic medication was discontinued at least for five half-life times except in five patients.

The study was approved by the Ethical Review Board of the institute, and written informed consent was obtained from all patients.

Intra-cardiac electroanatomic mapping
Electroanatomic mapping was performed using an electroanatomical mapping system (CARTO®XP system, Biosense Webster, Inc., Diamond Bar, CA, USA) with either a 7 Fr Navi-Star or ThermoCool catheter (Biosense Webster). A decapolar 6 Fr diagnostic catheter was placed in the CS. Three-dimensional isochronal activation maps were generated in sinus rhythm, gated to a stable CS reference signal.24Go,25Go The number of registered points was 112 ± 37 in LA and 71 ± 18 in RA. All points and respective ECG and intra-cardiac recordings in the maps were visually inspected. Local activation time was determined as the maximum or minimum of the first sharp deflection with an absolute value over 0.1 mV of the bipolar signal at the distal electrode pair of the catheter.9Go,26Go

P-wave morphology was examined to ensure sinus origin. The point was rejected if the beat was ectopic, the intra-cardiac signal was <0.1 mV in amplitude, or signs of catheter instability were seen.5Go,6Go,9Go,10Go,24Go–26Go If more than one sinus P-wave morphology were seen in a recording, each was analysed separately. When double potentials were found, the first was used except when it was a low frequency far-field potential.9Go All intra-cardiac electrogram data were gathered before starting the ablation procedure.

Electroanatomic maps (EAMs) of atrial activation were reconstructed by applying interpolated colour code adjustments of local activation times on recorded anatomic shape. The area of first activation in the LA was determined. Conduction through BB was assumed when the earliest activation was in upper third of LA, superior and leftward from the upper right pulmonary vein. Conduction through the rim of FO was assumed when earliest activation was within the middle third of LA, around the trans-septal puncture site. Conduction through CS region was assumed when the earliest activation was in the lowest 1 cm of LA, with activation front directing cranially. More than one electrical breakthrough site was regarded to exist when distinct conduction sites were activated within 15 ms and were separated by areas showing later activation.10Go According to the observed breakthrough sites, the patients were separated into BB, CS, FO, and combined (multisite activation) groups. The LA activation sequence was examined using both activation and propagation maps, and the direction of signal propagation was assessed visually. All electroanatomic signals were examined by two readers, and in case of discordance in breakthrough sites, consensus was reached after consulting an electrophysiologist experienced in cardiac mapping.

The onset of atrial activation was determined from the 12-lead ECG as the earliest time point where the signal could be separated from the baseline. The time from onset to the latest intra-cardiac LA activation was defined as the total atrial activation time. Total LA and RA activation times were determined from intra-cardiac recordings.

Magnetocardiographic method
Magnetocardiography recordings were performed in a magnetically shielded room (ETS-Lindgren Euroshield Oy, Eura, Finland) using a multichannel cardiomagnetometer (Elekta Neuromag Ltd, Helsinki, Finland) equipped with 33 triple sensor dc-SQUID units on a slightly curved surface with a diameter of 30 cm. In each unit, a magnetometer is overlaying two orthogonal planar gradiometers, the magnetometer coil direction being perpendicular to the sensor array (z-axis). The system measures the magnetic field Bz component and the spatial change of this component, the planar gradients, d(Bz)/dx and d(Bz)/dy.

Magnetocardiography was recorded over anterior chest, the centre of the sensor array positioned 15 cm below the jugular notch and 5 cm left from the midsternal line, in sinus rhythm over 7 min (Figure 1). Simultaneously, the limb leads of the standard ECG were recorded. Analogue signal pass-band was 0.03–300 Hz and sampling frequency of analogue-to-digital conversion was 1000 Hz. The data were averaged using atrial wave template and maximum cross correlation.27Go Atrial ectopic beats and excessively noisy sinus beats were rejected. If two distinct sinus P-wave morphologies were present, both were separately averaged. The onset and end of the P-wave as well as P-wave duration were automatically determined using 40 Hz high-pass filtering and a computerized algorithm as described earlier.27Go


Figure 1
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  		Figure 1 Recording and analysis of atrial magnetic fields. (A) The sensor arrangement of a 33 U triple sensor (99-channel) magnetometer. Superimposed on sensor array is the antero-posterior few of the left atrium by electroanatomic mapping. (B) Signal-averaged magnetic field density on each magnetometer channel over cardiac cycle. The onset and end of atrial signal are determined automatically using filtering technique. (C) Spatial distribution of the magnetic field Bz component over the middle part of atrial complex interpolated from the measurement using multipole expansion. The blue colour indicates flux out of the chest (–) and red colour flux into the chest (+). The step between two consecutive lines is 200 ft. (D) Pseudocurrent map derived by rotating magnetic field gradients by 90°. The red–yellow colour indicates the area of the top 30% of strongest currents, and the large arrow indicates their mean direction. Zero angle direction is pointing from subject's right to left and positive clockwise.

 
Time interval over the first 30 ms of the atrial complex was taken to represent the early part of RA activation. The time interval over 40–70 ms after the beginning of atrial complex was chosen to represent early part of LA activation and the latter half of the atrial wave to represent the later part of LA activation. The selection of time intervals was based on previous knowledge on the atrial activation sequence.4Go–7Go,10Go,11Go

Integrals of the magnetic field Bz component over the defined time intervals were interpolated at the sensor array plane using magnetic multipole expansion.28Go To characterize the orientation of the magnetic field, a pseudocurrent conversion was used.29Go The method is based on rotating the estimated planar gradients of the Bz component by 90°:


Formula

where ex and ey are the perpendicular unit vectors on the sensor array plane. The resulting arrow map provides a zero-order approximation (pseudocurrent map) for the underlying electric currents. To get a quantitative variable, the mean of the angles of the top 30% of the strongest pseudocurrents was calculated, zero angle direction pointing from subject's right to left and positive clockwise. The method is illustrated in Figure 1 and described in more detail in the Appendix.

The MCG map orientations during 40–70 ms after the onset of the atrial complex and over its last 50% were compared with LA breakthrough areas in EAM in each individual. The pseudocurrent angles in MCG maps were calculated for the whole patient group and for subgroups with different breakthrough sites. In addition, in six patients, the MCG map orientation of the integral over first 30 ms of atrial depolarization complex was compared with EAM of the RA. The P-wave morphology in limb leads of the standard ECG recorded during both mappings was used to capture similar atrial activity in each EAM and MCG map pairs.22Go An example of the EAM data and MCG data in the same timescale is shown in Figure 2.


Figure 2
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  		Figure 2 Example of atrial electroanatomic and magnetocardiographic mappings. Upper panel: electroanatomic map: isochronal activation maps of the right atrium and left atrium in antero-posterior (left) and postero-anterior (right) projections shown with colour-coded timescale. The step between two isochronal lines is 5 ms. The total atrial activation time in this case is 120 ms. The earliest right atrium activation is seen at upper lateral-septal part of the atrium (red star). The earliest left atrium activation is in the middle inter-atrial septum and 5 ms later at the area of Bachmann bundle and 10 ms later at the coronary sinus ostial area. The multisite activation pattern is best visible from the back—marked by thin arrows, the upper representing Bachmann bundle and lower coronary sinus routes. The activation fronts are pointed using arrows and symbols, dotted lines for right atrium, solid lines for initial left atrium, and dashed lines for later left atrium activation. Lower panel: magnetocardiographic map: pseudocurrent density maps representing the right atrium (first 30 ms), initial left atrium (40–70 ms), and later left atrium (last 50% of the whole atrium) activation time. Maps represent slightly tilted frontal plane projections with horizontal line from subject's right to left. The red–yellow areas correspond to the top 30% of the pseudocurrent amplitudes, and their mean angle is indicated with yellow arrows.

 
Statistical analysis
Continuous data are expressed as mean ± SD and categorical variables as numbers and proportion of positive cases in groups. Differences between the groups were examined using Student's t-test for continuous and the {chi}2 test for discrete variables. Coefficient of variation was used to compare measurements obtained by two different methods.

Angular data are expressed as mean angle and circular standard deviation (CSD). Angular–angular correlation coefficient was used to study the relationship of the MCG map orientations, and Watson's U2 test was used for comparison between groups.30Go A two-tailed P-value of <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusions
 Funding
 Appendix
 References
 
Demographic and clinical data of the patients are presented in Table 1. The mean age was 45 years and most patients were male. All had paroxysmal AF and most (89%) had no structural heart disease. In 2 patients, 2 different sinus P-wave morphologies were included resulting in total of 29 LA maps. In six patients also RA was mapped intra-cardially.


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  		Table 1 Demographic and clinical features

 
Electroanatomic maps
A single inter-atrial breakthrough site was observed in 19 of 29 maps (65%). The pathways were BB in 14 (48%), FO in 3 (10%), and CS in 2 (7%) cases by the invasive reference. In the remaining 10 of 29 cases (34%), the activation occurred through more than one pathway. Here, BB was included in six, FO in nine and CS in seven cases.

The directions of activation fronts by EAM during early LA activation, evaluated visually, were mainly leftward down, i.e. descending, in the BB group, leftward up, i.e. ascending, in the CS group, and more horizontal and variable in the FO and combined groups. The main direction of activation front during RA activation was mostly leftward down as illustrated in Figure 2.

The duration of total atrial activation by EAM was 117 ± 12 ms (Table 2). The earliest LA activation was detected 34 ± 9 ms after the onset of atrial complex. The duration of LA activation was 84 ± 14 ms. In six cases available, the duration of RA activation was 81 ± 8 ms. Both atria were activated simultaneously for 49 ± 12% of the total atrial activation time.


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  		Table 2 Atrial activation times and magnetocardiographic pseudocurrent orientation in whole study population and in subgroups formed according to left atrial breakthrough areas in electroanatomic mapping

 
Magnetocardiographic maps
The duration of filtered atrial wave by MCG was 115 ± 15 ms. The durations are shown for groups formed according to different LA breakthroughs in Table 2. The filtered atrial wave duration and total activation time in EAM showed 5.1% coefficient of variation.

The pseudocurrent direction in MCG maps over the first 30 ms of atrial complex, representing early RA activation, was mostly leftward down, with a mean angle of 43° (CSD 28°). Over the time interval of 40–70 ms from the onset of the atrial complex, the mean angle was 39° (CSD 30°). Over the time interval of last 50% of atrial complex, the mean angle was 3° (CSD 51°). An example of MCG maps over the selected time intervals of atrial depolarization is shown in Figure 2.

When both the early and late LA MCG maps were viewed together, three types of combinations emerged: Type 1 with both maps showing pseudocurrent orientation leftward down, Type 2 with the map over the 40–70 ms orienting leftward down and the map over last 50% of atrial signal orienting leftward up, and Type 3 with both maps orienting leftward up. Examples of these three types are illustrated in Figure 3.


Figure 3
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  		Figure 3 Electroanatomic and magnetocardiographic maps. (A) Isochronal activation electroanatomic maps during sinus rhythm in antero-posterior projection from four cases with different inter-atrial propagation routes. Left atrium is activated through Bachmann bundle, rim of the fossa ovalis, coronary sinus ostium, and combination of Bachmann bundle, fossa ovalis, and coronary sinus routes. Red colour identifies the earliest and purple colour the latest activation. The step between two isochronal lines is 5 ms. Activation breakthroughs are marked with black circles. Pseudocurrent density maps representing (B) initial left atrial (40–70 ms) and (C) later left atrial (last 50%) activation from respective cases. Maps represent slightly tilted frontal plane projections with horizontal line from subject's right to left. The red–yellow areas correspond to the top 30% of the pseudocurrent amplitudes and their mean angle, the magnetocardiographic map orientation is indicated with large yellow arrows. The Types 1, 2, and 3 (at the bottom) refer to the classification based on pseudocurrent direction in the two magnetic field maps.

 
Relationship between pseudocurrent directions and left atrium breakthrough sites
The activation fronts in MCG maps differed between subgroups allocated with regard to LA breakthrough sites in EAMs. Over the time interval 40–70 ms during the atrial complex, the pseudocurrent mean angle in the BB group pointed leftward down, more horizontally in the FO and combined groups, and leftward up in the CS group, as indicated in Table 2 and illustrated in Figure 3. The distribution of magnetic field orientation in the BB group (n = 14) was significantly different from that in other groups (n = 15) (P < 0.02). Overlapping of the multisite breakthrough group with other groups decreased the separating power of this measure, as seen in Figure 4.


Figure 4
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  		Figure 4 The pseudocurrent mean angles of 40–70 ms (x-axis) and last 50% (y-axis) time intervals in the x–y plot. Each case is labelled according to the left atrium breakthrough site in invasive mapping: solid circle = Bachmann bundle, solid triangle = coronary sinus, open square = fossa ovalis, multiplication symbol = Combination. In cases with a solitary conduction pathway, both angles shift to less negative when moving from Bachmann bundle to fossa ovalis and coronary sinus. However, angles in cases with multiple pathways overlap. Yet, last 50% map helps in separating the combined pathways from the solitary Bachmann bundle pathway. Allocation to three different types, based on the two magnetocardiographic map orientations, permits identification of conduction pathways in 27 of the 29 cases.

 
The direction of pseudocurrent angle over the latter half of atrial complex was positive in all cases in BB group and in 2 cases of combined pathways (BB & CS and BB & FO), but negative in all other 13 maps. Also during this time interval, the distribution of magnetic field orientation in the BB group was significantly different from that in other groups (P < 0.001).

Magnetic field orientations over the initial and later part of LA activation showed high mutual correlation (angular–angular r = 0.89, P < 0.001) in cases with single breakthrough via BB or CS, but differed in cases with FO and combined breakthroughs. The combination of two LA MCG maps yielded three different types. All 14 cases of solitary breakthrough via BB had Type 1 magnetic field maps (Table 3). The three cases with solitary FO breakthrough had Type 2 maps and both cases with solitary CS breakthrough had Type 3 maps. In combined pathways (n = 10), Type 2 maps were found in eight cases and Type 1 maps in two cases.


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  		Table 3 The relationship between left atrial breakthrough site in electroanatomic mapping and type of magnetic field orientation over the early (40–70 ms) and later (last 50%) part of left atrial depolarization analysed from magnetocardiographic recordings

 
Overall, by using the MCG map type as a criterion, the LA breakthrough site was correctly identified to BB, CS, and FO or combined pathways in 27 of 29 cases (93%). Only the solitary breakthrough via FO could not be separated from the combined pathways.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusions
 Funding
 Appendix
 References
 
Main findings
The present study demonstrates that the variation in impulse propagation to the LA during sinus rhythm can be assessed non-invasively by magnetocardiography. Using the pseudocurrent pattern of the initial and later parts of LA signal, three distinct LA breakthrough sites corresponding to anatomical areas of BB, inter-atrial septum at the vicinity of FO, and the CS ostium could be separated. Judged by pseudocurrent directions in MCG maps, the signal propagation during the initial and later parts of LA activation was directed leftward down in BB breakthrough, upwards in CS breakthrough, and variably horizontal left when breakthrough area was FO or multiple breakthroughs appeared. Overall, the breakthrough sites could be classified correctly into these categories by MCG in 27 of the 29 cases (93%).

Invasive assessment of connections to the left atrium
In concordance with earlier studies,3Go–6Go,9Go most of our patients showed conduction through BB, either as a solitary route or in combination with other routes. However, a remarkable 27% minority of patients showed none of the LA activated through the BB route. This is supported by an earlier non-contact mapping study where the BB route was not observed in 12 of 21 patients7Go as well as by a post-mortem anatomic study where BB was not seen in half of the AF patients or controls.16Go The activation of LA through multiple conduction pathways was found in approximately one-third of our patients, which is in the range of 10–43% as reported earlier.7Go,9Go In two of our patients, two activation routes alternated during recording indicating that temporary factors can modify the conduction pattern. A shift in an endocardial LA breakthrough site was also demonstrated by Markides et al.7Go

The durations of whole atrial activation and LA activation measured in the present study were comparable with the durations of 120 ± 24 and 80 ± 11 ms reported by Lemery et al.5Go in AF patients treated with catheter ablation, and slightly longer than the duration of LA activation of 65 ± 4 ms reported by Markides et al.7Go in lone AF patients. The LA activation started at 34 ms on average in our study, similar to earlier observations.5Go–7Go,11Go

Since RA activation is rather stable according to previous4Go–6Go,10Go,11Go,24Go and present observations, variation during the 40–70 ms from atrial onset apparently has the capability to reveal different patterns of the superimposed LA activation. This justifies the use of the middle part of atrial depolarization wave to analyse different LA activation patterns.

Interpreting atrial activation by magnetocardiographic mapping
In some recent works, interpolation of the current density maps,31Go or independent component of multichannel magnetic field signal,32Go on three-dimensional heart model have been used. However, the two-dimensional presentation of the pseudocurrent angle utilized in this study29Go,33Go seems to represent adequately the main direction of electrical signal propagation. The findings support the concept that two-dimensional pseudocurrent map can provide an estimate of the summation of real three-dimensional atrial currents and their temporal propagation.29Go,33Go

It has been previously suggested that the LA breakthrough site is reflected in the LA activation pattern.5Go,7Go,8Go,11Go In the present study, the LA activation fronts over the initial part of LA activation differed between BB, CS, and FO conduction pathway subgroups. However, the FO activation route, as solitary or in combination, could not be clearly distinguished based on the initial LA activation alone. When the information over the latter half of atrial complex was combined with that of initial LA, the MCG maps could be divided into three different types, each of which was suggestive to a certain breakthrough site. The types were specific to activation through BB and CS, but the activation through the margin of FO seems to create less distinct activation pattern. Since FO was involved in 8 of the 10 cases in the combined group, the activation through FO might confound assessment of conduction through BB. The findings are comparable to orthogonal ECG by which the single route activation through FO or BB could not be separated from multisite activation including these pathways.9Go

Overall, the findings imply that non-invasive MCG mapping can be utilized to assess conduction to the LA during sinus rhythm. Although MCG has better localizing ability compared with electrocardiography,21Go the observations nevertheless encourage to develop computational analysis of data acquired by standard or modified electrocardiographic lead sets.9Go,34Go,35Go With more sophisticated applications, MCG technology might provide a new means of non-invasive mapping of atrial arrhythmia foci and re-entrant circuits.

Clinical associations
The prolongation and morphological changes of P-wave have been related to inter-atrial block and propensity to AF.12Go,17Go,18Go In addition to inter-atrial conduction impairment, conduction barriers within the LA have been shown.7Go,8Go It is also possible that collision of electrical impulses through different propagation routes may be linked to the pathogenesis of AF. Recognizing the inter-atrial conduction pathway may assist in identifying subgroups for patient-tailored therapy.

Catheter ablation of the RA septal region36Go and CS connections37Go or trans-section of the anterior LA38Go have been effective in the treatment of AF in some patients. Ablation of CS and FO areas has altered inducibility to AF in an animal model.39Go Thus, all the three inter-atrial conduction pathways seem to have relevance in generation of AF, and knowledge on atrial conduction pathways may have impact in refining methods for the ablation treatment in patients with paroxysmal AF.

Limitations
Correspondence of electroanatomic and MCG atrial mappings was examined in patients with relatively normal hearts and highly symptomatic paroxysmal AF. Conductive properties might be different in healthy subjects and when AF is associated with heart diseases. The time windows for MCG map analysis may need adjustment to cover the intended atrial compartments in markedly enlarged atria. The influence of scars to MCG maps could not be evaluated in this patient series mostly without structural heart disease.

The local representativeness of recorded intra-cardiac signals is crucial for construction of the maps, especially around the postulated pathways. Registering potentials can be technically challenging in the inter-atrial septum due to far-field potentials from nearby structures. The number of patients in conduction pathway subgroups was small and therefore the performance of the technique needs to be tested in larger populations. Due to necessity to rely on visually observed direction of signal propagation in electroanatomic mapping, the authenticity of direction of atrial activation determined by MCG mapping could not be ensured. Yet, this information is not necessary for validation of the ability to identify inter-atrial conduction pathways.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
Funding
 Appendix
 References
 
Magnetocardiographic mapping over the frontal chest and subsequent analysis applying pseudocurrent distribution are capable of identifying different activation breakthrough sites in the LA during sinus rhythm with an adequate accuracy. This non-invasive technique may also be used for assessing inter-atrial conduction in large patient series and healthy subjects, in which the invasive measurements are not possible. Recognizing the inter-atrial conduction pathways may assist in understanding the pathogenesis of AF and identifying subgroups for patient-tailored therapy.

Conflict of interest: none declared.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Funding
Appendix
 References
 
This study was supported by grants from the Finnish Foundation for Cardiovascular Research, Helsinki, Finland and Alfred Kordelin Foundations, Helsinki, Finland.


   Appendix
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Funding
 Appendix
References
 
Interpolation with magnetic multipole expansion
For calculation of the magnetic field map orientation and visualization of the measured field, the magnetic field was interpolated from the measured data using magnetic multipole expansion.28Go Magnetic multipole expansion is a series expansion of the magnetic scalar potential, analogous to the electric multipole expansion.

Static magnetic field can be expressed by a scalar potential. In bioelectromagnetic fields, the rate of change is relatively low, and generally utilized the assumption of static fields is valid. Then, in source-free region, such as the sensor surface, the curl of the magnetic flux vanishes (Formula ) and the magnetic field can be represented as the gradient of the magnetic scalar potential (Formula ). Because magnetic field has no sources (Formula ), the magnetic scalar potential obeys the Laplace equation (Formula ). We use truncated general serial solution of the Laplace equation in spherical co-ordinates28Go


Formula

where Alm are coefficients for the sources inside a spherical surface and Ylm the spherical harmonic functions. We set the expansion origin at 15 cm below the centre of the sensor area (approximately at the heart). Using Formula and the sensor geometry for all sensors, we get a set of equations for coefficients Alm. These equations can be expressed in matrix form by defining transfer matrix T and the corresponding vector Formula of the multipole coefficients Alm. Then the coefficients are found from the measured signals Formula by Formula

The interpolation is based on virtual sensors and composing transfer matrix T' for them, as explained above. The interpolated signals are then obtained as Formula

For magnetic field interpolation, a square grid of points was generated at the sensor array surface with grid constant of 0.5 cm and diameter of 26 cm. The field component Bz perpendicular to the surface was interpolated at each time instant by assuming a virtual magnetometer at each grid point. Surface gradients {partial}(Bz)/{partial}x and {partial}(Bz)/{partial}y were calculated as the difference of adjacent point values of interpolated Bz data divided by the 0.5 cm separation.

Determining and parameterization of the magnetic field map orientation
In this work, the MCG maps were visualized and parameterized using pseudocurrent transformation, originally presented by Cohen and Hosaka.29Go Pseudocurrents are 90° rotated magnetic field surface gradient vectors, Formula that reflect the underlying source currents. We used pseudocurrent direction to determine the MCG map orientation.

For each MCG map, the distribution of pseudocurrent magnitude and direction were computed, with zero angle direction pointing from subject's right to left and positive clockwise. In order to produce a robust measure of MCG map orientation and to visually assess its significance, the pseudocurrents with relative strength above 70% in each map were selected for further analysis. The orientation of the MCG map was defined as the mean direction of the selected pseudocurrents.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Funding
 Appendix
 References
 
[1] O'Donnell D, Bourke JP, Furniss SS. Interatrial transseptal electrical conduction: comparison of patients with atrial fibrillation and normal controls. J Cardiovasc Electrophysiol (2002) 13:1111–7.[CrossRef][Web of Science][Medline]

[2] Oral H, Ozaydin M, Chugh A, Scharf C, Tada H, Hall B, et al. Role of coronary sinus in maintenance of atrial fibrillation. J Cardiovasc Electrophysiol (2003) 14:1329–36.[CrossRef][Web of Science][Medline]

[3] Hindricks G, Kottkamp H. Simultaneous noncontact mapping of left atrium in patients with paroxysmal atrial fibrillation. Circulation (2001) 104:297–303.[Abstract/Free Full Text]

[4] De Ponti R, Ho SY, Salerno-Uriarte JA, Tritto M, Spadacini G. Electroanatomic analysis of sinus impulse propagation in normal human atria. J Cardiovasc Electrophysiol (2002) 13:1–10.[CrossRef][Web of Science][Medline]

[5] Lemery R, Soucie L, Martin B, Tanq AS, Green M, Healey J. Human study of biatrial electrical coupling: determinants of endocardial septal activation and conduction over interatrial connections. Circulation (2004) 110:2083–9.[Abstract/Free Full Text]

[6] Lemery R, Birnie D, Tang AS, Green M, Gollob M, Hendry M, et al. Normal atrial activation and voltage during sinus rhythm in the human heart: an endocardial and epicardial mapping study in patients with a history of atrial fibrillation. J Cardiovasc Electrophysiol (2007) 18:402–8.[CrossRef][Web of Science][Medline]

[7] Markides V, Schilling RJ, Ho SY, Chow AW, Davies DW, Peters NS. Characterization left atrial activation in the intact human heart. Circulation (2003) 107:733–9.[Abstract/Free Full Text]

[8] Betts TR, Roberts PR, Morgan JM. High-density mapping of left atrial endocardial activation during sinus rhythm and coronary sinus pacing in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol (2004) 15:1111–7.[CrossRef][Web of Science][Medline]

[9] Holmqvist F, Husser D, Tapanainen JM, Carlson J, Jurkko R, Xia Y, et al. Interatrial conduction can be accurately determined using standard 12-lead electrocardiography: validation of P-wave morphology using electroanatomic mapping in man. Heart Rhythm (2008) 5:413–8.[Medline]

[10] Roithinger FX, Cheng J, SippensGroenewegen A, Lee RJ, Saxon LA, Scheinman MM, et al. Use of electroanatomic mapping to delineate transseptal atrial conduction in humans. Circulation (1999) 100:1791–7.[Abstract/Free Full Text]

[11] Cosio FG, Martin-Penato A, Pastor A, Núnez A, Montero MA, Cantle CP, et al. Atrial activation mapping in sinus rhythm in the clinical electrophysiology laboratory: observations during Bachmann's bundle block. J Cardiovasc Electrophysiol (2004) 15:524–31.[Web of Science][Medline]

[12] Bayés de Luna A, Cladellas M, Oter R, Torner P, Guindo J, Marti V, et al. Interatrial conduction block and retrograde activation of the left atrium and paroxysmal supraventricular tachyarrhythmia. Eur Heart J (1988) 9:1112–8.[Abstract/Free Full Text]

[13] Bachmann G. The inter-auricular time interval. Am J Physiol (1916) 41:309–20.[Free Full Text]

[14] Wang K, Ho SY, Gibson DG, Anderson RH. Architecture of atrial musculature in humans. Br Heart J (1995) 73:559–65.[Abstract/Free Full Text]

[15] Chauvin M, Shah D, Haissaguerre M, Marcellin L, Brechenmacher C. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation (2000) 101:647–52.[Abstract/Free Full Text]

[16] Platonov PG, Mitrofanova LB, Chireikin LV, Olsson SB. Morphology of interatrial conduction routes in patients with atrial fibrillation. Europace (2002) 4:183–92.[Free Full Text]

[17] Ariyarajah V, Asad N, Tandar A, Spodick DH. Interatrial block: pandemic prevalence, significance and diagnosis. Chest (2005) 128:970–5.[Free Full Text]

[18] Platonov PG, Carlson J, Ingemansson MP, Roijer A, Hansson A, Chireikin LV, et al. Detection of interatrial conduction defects with unfiltered signal-averaged P wave ECG in patients with lone atrial fibrillation. Europace (2000) 2:32–41.[Abstract/Free Full Text]

[19] Siltanen P. Magnetocardiography. In: Comprehensive Electrocardiology Volume II—Macfarlane P, Lawrie TDV, eds. (1989) Oxford: Pergamon Press. 1405–38.

[20] Korhonen P, Montonen J, Endt P, Mäkijärvi M, Trahms L, Katila T, et al. Magnetocardiographic intra-QRS fragmentation analysis in the identification of patients with sustained ventricular tachycardia after myocardial infarction. Pacing Clin Electrophysiol (2001) 24:1179–86.[Medline]

[21] Fenici R, Nenonen J, Pesola K, Korhonen P, Lötjönen J, Mäkijärvi M, et al. Nonfluroscopic localization of an amagnetic stimulation catheter by multichannel magnetocardiography. Pacing Clin Electrophysiol (1999) 22:1210–20.[Medline]

[22] Mäntynen V, Vitikainen A-M, Koskinen R, Mäkijärvi M, Toivonen L, Montonen J. Magnetocardiography is sensitive to differences in inter-atrial conduction in patients with paroxysmal lone atrial fibrillation. In: Proceedings of the 15th International Conference on Biomagnetism—Cheyne D, Ross B, Stroink G, Weinberg H, eds. (2007) Vancouver, BC, Canada: Elsevier. 508–11.

[23] Koskinen R, Väänänen H, Mäntynen V, Montonen J, Nenonen J, Lehtonen L, et al. Field heterogeneity in magnetocardiographic atrial signals in patients with focally-triggered lone atrial fibrillation (Abstract). Heart Rhythm (2004) 1:226.

[24] Smeets JL, Ben-Haim SA, Rodriquez LM, Timmermans C, Wellens HJ. New method for nonfluoroscopic endocardial mapping in humans. Circulation (1998) 97:2426–32.[Abstract/Free Full Text]

[25] Gepstein L, Hayam G, Shlomo A, Ben-Haim SA. A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart. Circulation (1997) 95:1611–22.[Abstract/Free Full Text]

[26] Weiss C, Willems S, Rueppel R, Hoffmann M, Meinertz T. Electroanatomic mapping (CARTO) of ectopic atrial tachycardia: impact of bipolar and unipolar local electrogram annotation for localization the focal origin. J Interv Card Electrophysiol (2001) 5:101–7.[CrossRef][Web of Science][Medline]

[27] Koskinen R, Lehto M, Väänänen H, Rantonen J, Voipio-Pulkki L-M, Mäkijärvi M, et al. Measurement and reproducibility of magnetocardiographic filtered atrial signal in patients with lone atrial fibrillation and in healthy subjects. J Electrocardiol (2005) 38:330–6.[CrossRef][Medline]

[28] Jackson JD. Classical Electrodynamics (1999) 3rd ed. New York, NY: John Wiley & Sons, Inc.

[29] Cohen D, Hosaka H. Part II—Magnetic field produced by a current dipole. J Electrocardiol (1976) 9:409–17.[CrossRef][Web of Science][Medline]

[30] Zar JH. Biostatistical Analysis. (1999) 4th ed. Upper Saddle River, NJ: Prentice-Hall. 630. 649.

[31] Kim D, Kim K, Lee YH, Ahn H. Detection of atrial arrhythmia in superconducting quantum interference device magnetocardiography; preliminary result of a totally-non-invasive localization method for atrial current mapping. Interact Cardiovasc Thorac Surg (2007) 6:274–9.[Abstract/Free Full Text]

[32] Nakai K, Kawazoe K, Izumoto H, Tsuboi J, Oshima Y, Oka T, et al. Construction of a three-dimensional outline of the heart and conduction pathway by means of a 64 channel magnetocardiogram in patients with atrial flutter and fibrillation. Int J Cardiovasc Imaging (2005) 21:555–61.[Medline]

[33] Haberkorn W, Steinhoff U, Burghoff M, Kosch O, Morguet A, Koch H. Pseudo current density maps of electrophysiological heart, nerve or brain function and their physical basis. Biomagn Res Technol (2006) 4:5.[CrossRef][Medline]

[34] Edenbrandt J, Pahlm O. Vectorcardiogram synthesized from 12-lead ECG: superiority of the inverse Dower matrix. J Electrocardiol (1988) 21:361–7.[CrossRef][Web of Science][Medline]

[35] Carlson J, Havmöller R, Herreros A, Platonov P, Olsson B. Can orthogonal lead indicators of propensity to atrial fibrillation be accurately assessed from the 12-lead ECG? Europace (2005) 7:39–48.[Free Full Text]

[36] Gaita F, Riccardi R, Calò L, Scaglione M, Garberoglio L, Antolini R, et al. Atrial mapping and radiofrequency catheter ablation in patients with idiopathic atrial fibrillation. Electrophysiological findings and ablation results. Circulation (1998) 97:2136–45.[Abstract/Free Full Text]

[37] Haissaguerre M, Hocini M, Takahashi Y, O'Neill MD, Pernat A, Sanders P, et al. Impact of catheter ablation of the coronary sinus on paroxysmal or persistent atrial fibrillation. J Cardiovasc Electrophysiol (2007) 18:378–86.[Medline]

[38] Sanders P, Jais P, Hocini M, Hsu LF, Scavée C, Sacher F, et al. Electrophysiologic and clinical consequences of linear catheter ablation to transect the anterior left atrium in patients with atrial fibrillation. Heart Rhythm (2004) 1:176–84.[CrossRef][Web of Science][Medline]

[39] Ott P, Kirk MM, Koo C, He DS, Bhattacharya B, Buxton A. Coronary sinus and fossa ovalis ablation: effect on interatrial conduction and atrial fibrillation. J Cardiovasc Electrophysiol (2007) 18:310–7.[Medline]


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