Where to draw the mitral isthmus line in catheter ablation of atrial

European Heart Journal (2005) 26, 689–695
doi:10.1093/eurheartj/ehi095
Clinical research
Where to draw the mitral isthmus line in catheter
ablation of atrial fibrillation: histological analysis
Fred H.M. Wittkampf1*, Matthijs F. van Oosterhout2, Peter Loh1,
Richard Derksen1, Evert-jan Vonken3, Piet J. Slootweg1, and Siew Yen Ho4
1
Heart Lung Center Utrecht, University Medical Center E03-406, PO Box 85500, 3508 GA, Utrecht, The Netherlands
University Medical Center Utrecht, Department of Pathology, Utrecht, The Netherlands
3
University Medical Center Utrecht, Department of Radiology, Utrecht, The Netherlands
4
Department of Paediatrics, National Heart and Lung Institute, and Royal Brompton Hospital, London, UK
2
Received 6 October 2004; revised 6 October 2004; accepted 25 November 2004; online publish-ahead-of-print 6 January 2005
KEYWORDS
Atrial fibrillation;
Catheter ablation
Aims A linear lesion between the left inferior pulmonary vein orifice and mitral
annulus, the so-called mitral isthmus, may improve the success of catheter ablation
for atrial fibrillation. Gaps in the lesion line, however, may facilitate left atrial
flutter. The aim of the study was to determine the optimal location of the lesion
line by serial sectioning of the isthmus area.
Methods and results In a post-mortem study of 16 patients with normal left atria,
serial sections of the isthmus area from 10 mm superior to and 30 mm inferior to
the isthmus were studied by light microscopy. The length of the isthmus was
35 + 7 mm. On average, the muscle sleeve around the coronary sinus ended 10 mm
inferior to the isthmus. The prevalence of a ramus circumflexus ,5 mm from the
endocardial surface, decreased from 60% in the most superior section to 0% in the
most inferior section. Atrial arteries were frequently present in all sections.
Conclusions The thickness of atrial myocardium, the ramus circumflexus sometimes
very close to the endocardium, a myocardial sleeve around the coronary sinus, and
local cooling by atrial arteries and veins may complicate the creation of conduction
block in the mitral isthmus.
Introduction
Catheter ablation of atrial fibrillation has evolved from
ablation of arrhythmogenic foci within the pulmonary
veins (PV) to complete electrical isolation of the PV,
often guided by perimetric mapping with a multi-polar
loop catheter positioned at the rim of each of the PV
ostia.1–4 Adding an ablation line connecting the inferior
margin of the ostium of the left inferior PV (LIPV) to the
mitral annulus appears to increase the success rate of
treating atrial fibrillation by catheter ablation.5–9
Another approach is to encircle both right and left pairs
* Corresponding author.
of PV ostia by multiple lesions followed by a linear lesion
connecting both areas and another linear lesion from the
inferior margin of the left-sided encircling lesion to the
mitral annulus.3,10,11 In their most extensive form, both
techniques thus include a linear lesion in the posteroinferior wall of the left atrium through an area described by
electrophysiologists as the mitral isthmus. In practice,
however, the creation of complete isthmus block is not
always successful. Gaps in the lesion line may result in conduction delay and facilitate left atrial flutter.4,9,12–14
Recently Becker15 analysed the anatomy of the isthmus
section in 20 hearts.16 The aim of the present study was
to analyse a broader part of that isthmus to assess the
optimal location for such a lesion line.
E-mail address: [email protected]
& The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: [email protected]
690
Methods
The investigational protocol was approved by the ethics committee of the University Medical Center. We examined the heart
specimens from 16 autopsies carried out routinely. The left
atrium was opened from the anterior aspect to expose the
posterior and inferior parts of its wall. From each left atrium,
we excised a piece of tissue that included the veno-atrial junctions between both upper PV and the left atrioventricular junction (Figure 1 ). The excised pieces were mounted on a flat
support and fixed in formalin. After fixation, the length of the
mitral isthmus, defined as the line from the inferior margin of
the LIPV ostium and perpendicular to the mitral annulus, was
measured along the endocardial surface. Each piece was then
cut longitudinally through the isthmus and further divided by
making parallel cuts at 10 mm intervals, and approximately
equally as long as the isthmus section (Figure 1 ). Because
electrophysiologists usually orient relative to a catheter in the
coronary sinus, it is more convenient to refer to these sections
as being distal or proximal relative to the index cut through
the isthmus.
Full-face histological sections were prepared from each
piece of tissue and stained with Van Gieson’s stain. All sections
were photographed digitally and analysed using standard
software (NIH-Image). Over the complete length of each
section, we measured the ‘myocardial depth’ by noting the distance between the endocardium and the most subepicardial
muscle fibres at 0.5- to 1-mm intervals. This measurement did
not include the myocardial sleeve around the vein. We further
recorded the positions of the great cardiac vein or its continuation, the coronary sinus (CS), and all arteries and veins
with a diameter .0.25 mm, relative to the endocardium and
mitral annulus (Figure 1 ). Since cuts at 10 mm intervals did
not allow for a precise localization of the transition from the
CS to the great cardiac vein, we therefore used the term
‘vein’ to refer to both structures, acknowledging that the CS is
usually invested in a myocardial sleeve whereas the great
cardiac vein is usually devoid of sleeve. Anatomically, the
junction between the great cardiac vein and CS is usually
taken to be at the entrance of the vein (or ligament) of Marshall,
Figure 1 Posterior wall of the left atrium. Serial sections were taken at
10 mm intervals perpendicular to the mitral annulus. The second section
from the right is the shortest connecting line between the lower border of
the LIPV ostium and mitral annulus that we termed the mitral isthmus. In
that area, cavities in which the tip of an ablation catheter can easily get
entrapped are present. RIPV: right inferior pulmonary vein.
F.H.M. Wittkampf et al.
or at the valve of Vieussens (Figure 2 ). Neither structure is
readily visible on fluoroscopy.
Using the inner wall of the veins and the external elastic
lamina of the arteries as boundaries, the vessel diameters
were calculated by assuming a circular vessel perimeter. For
vessels showing an oval cross-sectional shape and a thinner
wall thickness along the short axis, we assumed a slanted
course relative to the section plane and then the short axis
was taken as vessel diameter. Data are given as mean + s.d.
Results
The mean age of patients was 52 + 16 years. The cause
of death was non-cardiac in all 16 patients. Left ventricular myocardial infarcts were found in four patients
including a small sub-endocardial infarct in one patient;
the other patients had none or only mild cardiac pathology. Macroscopically, the left atria were not dilated and
none of the patients had a history of atrial fibrillation.
The 12-lead electrocardiograms that were available for
eight patients all demonstrated sinus rhythm with
normal P-wave morphology. One patient had left ventricular hypertrophy related to hypertension.
In all 16 patients, the tissue sample included the mitral
isthmus section and at least two proximal sections
(Figure 1 ). The piece 10 mm distal to the isthmus was
available in 15 patients while the most proximal section
at 30 mm from the isthmus and close to the atrial
septum could be harvested in 13/16 patients.
Section 10 mm distal to isthmus
In the section 10 mm distal to the mitral isthmus,
available in 15/16 patients, the vein was present in 14
patients. None had a muscular venous sleeve. The
average maximum distance between endocardium and
subepicardial muscle fibres (myocardial depth) was
1.7 + 0.7 mm for the first 5 mm. Measured over the complete length of the 15 available sections, the average of
the maximum myocardial depth was 3.6 + 0.8 mm and
Figure 2 This view of the epicardial aspect of a human heart shows the
relationship of the mitral isthmus (broken line) to the great cardiac
vein/coronary sinus transition indicated by the blue arrow.
Mitral isthmus
691
4.5 mm in all cases (Table 1 ). In most sections, the
maximum myocardial depth was found approximately in
the middle of the section just above the vein. Arteries
were often present. Based on their size and location in
successive sections, nine arteries (in nine patients)
were identified as the ramus circumflexus (RCx) or a
branch of it nourishing ventricular myocardium. In six
patients, its distance to the endocardium was ,5 mm
and one of these arteries was in direct contact with the
atrial myocardium.
complete and continuous with the atrial myocardium
(Tables 1–2 ).
A RCx was identified in seven sections in seven patients
(Figures 3 and 4, Table 1 ). In five patients, the RCx was
closer than 5 mm from the endocardium of which three
were closer than 2 mm from the endocardium and in
direct contact with the atrial myocardium. Of these
five RCx, one was located above the level of the vein;
two were sandwiched between vein and endocardium,
and another two were located between the vein and
mitral annulus.
Isthmus section
The length of the isthmus was 35 + 7 mm, range
23–50 mm (Table 1 ). Again, the atrial myocardium was
relatively thin within the first 5 mm from the annulus
with an average maximum myocardial depth of only
1.5 + 0.7 mm, range 0.3–3.3 mm (Figure 3A–C). The
maximum myocardial depth was most often found
approximately in the middle of the section just above
the vein. The average of the maximum myocardial
depth was 3.8 + 0.9 mm, range 2.2–5.5 mm (Table 1 ).
A muscular sleeve around the vein was present in three
patients. In two of these three patients, this sleeve was
incomplete; very thin muscle fibres only partly (,30%)
covered the perimeter of the vein and these muscle
fibres were not connected to atrial myocardium at that
level (Figure 3A ). In one patient, the sleeve was
Section 10 mm proximal to isthmus
The muscular sleeve around the vein was present in
11/16 patients. It was complete and connected to atrial
myocardium in eight patients (Figure 3C ), but incomplete and not connected to atrial myocardium at
this level in the three other patients. The average
maximum myocardial depth was 5.3 + 2.5 mm. Here
too, the myocardial wall was thin near the annulus:
the average maximum myocardial depth was 1.6 mm
for the first 5 mm near the annulus. The maximum myocardial depth was most often found approximately in
the middle of the section just above the vein. In five
patients, the RCx was present in this section and three
of these arteries were ,5 mm from the endocardium.
Table 1 Data of all sections
Proximal Mitral isthmus ! Distal
Sectionsa
n
Length, mm
Maximum myocardial depth, mmb
Maximum myocardial range, mm
Vein
Present, n (%)
Diameter, mm
Distance to annulus, mm
Muscular sleeve, n (%)
Connected sleeve, n (%)
RCx
n (%)
Diameter, mm
Depth, mm
n with depth ,5 mm
n embeddedc
Atrial arteries .0.25 mm
n
n with depth ,5 mm
Atrial veins .0.25 mm
n
n with depth ,5 mm
230 mm
220 mm
210 mm
0 mm
10 mm
13
32 + 9
5.2 + 1.8
2.6 2 8.4
16
29 + 8
4.3 + 1.7
2.5 2 8.6
16
30 + 7
4.0 + 1.6
1.9 2 7.6
16
35 + 7
3.8 + 0.9
2.2 2 5.5
15
37 + 9
3.6 + 0.8
2.0 2 4.5
13 (100)
5.6 + 1.8
11.1 + 3.7
12 (92)
12 (92)
16 (100)
4.3 + 1.1
11.3 + 3.2
15 (94)
14 (88)
16 (100)
3.6 + 1.0
9.7 + 2.6
11 (69)
8 (50)
16 (100)
3.5 + 0.9
8.4 + 2.7
3 (19)
1(6)
14 (88)
3.1 + 0.9
6.2 + 2.7
0
0
0
–
–
0
0
1(6)
2.8
3.4
1
1
5 (31)
2.3 + 0.4
4.5 + 2.7
3
1
7 (44)
2.5 + 0.6
3.9 + 2.3
5
3
9 (60)
2.8 + 0.7
4.6 + 2.5
6
1
22
19
20
19
14
12
22
20
20
17
5
3
4
3
5
4
7
6
4
2
a
The length of the isthmus is measured along the endocardial surface from the inferior margin of the left inferior pulmonary vein ostium to the base
of the mitral leaflet. The other sections were collected with approximately the same length as the isthmus section.
b
Maximum myocardial depth, maximum distance between endocardium and most subepicardial muscle fibres.
c
Embedded, in direct contact with atrial myocardium.
692
F.H.M. Wittkampf et al.
Table 2 Obstacles in individual patients
Proximal Mitral !Distal
isthmus
Patient 230 mm
220 mm
210 mm
0 mm
10 mm
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
S
S, M
S
S, M
S
S, M
—
S
S
S
S, M, RCx
—
S
S
S
S, M
S
S, M
—
S
—
M
RCx
—
S
RCx
S, M, RCx
—
S
—
S
S, M
—
—
RCx
—
—
RCx
RCx
—
—
RCx
M, RCx
—
S
—
—
—
—
—
RCx
—
—
RCx
RCx
RCx
—
RCx
n.a.
—
—
—
RCx
—
n.a.
S
S, M
S, M
S
n.a
S
S
S
S
S, M
M
S
n.a.
S
S, M
RCx, RCx , 5 mm from the endocardial surface. M, myocardial
depth . 5 mm. S, the presence of a complete muscular sleeve
around the vein. n.a., not available.
More proximal sections
The prevalence of the muscular sleeve around the vein
increased while the prevalence of the RCx decreased.
(Table 1, Figure 5 ) At 30 mm proximal to the isthmus,
the RCx was absent in all sections while the myocardial
sleeve was present in 12/13 cases (Tables 1 and 2 ).
All sections
Figure 3 Three representative sections. (A) Isthmus section with an
occluded RCx in close contact with atrial myocardium and at only
1.4 mm from the endocardium. This section also shows a very thin and
incomplete muscular sleeve around the vein (V). (B) Isthmus section
with an RCx and branch (RCx-b) and two atrial arteries. RCx-b is
located below the level of the annulus and therefore not included in
the data. All three arteries above the annulus are completely embedded
within atrial myocardium. This section also happened to go through the
middle of one of the isthmus crevices and shows the extremely thin myocardial wall at this location. (C) A section 10 mm proximal to the isthmus
with a complete muscular sleeve around the vein. The creation of complete conduction block will only be possible when ablations include application(s) from inside the vein. Sections shown in panels B and C were bent
to fit in the embedding cassette.
There was some increase in myocardial depth from distal
to proximal sections (Table 1 ). Overlap of atrial myocardium onto the endocardial aspect of the mitral valve
leaflet was only found in one patient in each of the
four most distal section groups, but this overlap was
always ,0.5 mm. In all sections where an incomplete
myocardial sleeve was present around the vein, it was
also not connected to atrial myocardium at that level.
Atrial arteries and atrial veins .0.25 mm in diameter,
often embedded in atrial myocardium, were frequently
present at all section levels (Figure 4, Table 1 ).
A notable observation relevant for catheter ablation is
the presence of crevices in approximately the middle
area of the mitral isthmus, close to the base of the left
atrial appendage, in 15/16 patients (Figure 1 ). These
depressions, presumed to be the valleys between
remnants of pectinate muscles that extended from the
left atrial appendage, were present in an otherwise
very smooth area. Importantly, many of them appeared
large enough to engage the tip of an ablation electrode.
The remaining wall thickness at the bottom of the
depressions could be extremely thin (Figure 3B ).
Mitral isthmus
693
isthmus in only 1/16 patient, and 30 mm proximal to
the isthmus in 0/13 patients (Table 2 ).
Discussion
Figure 4 Prevalence of arteries in the 16 isthmus sections classified
according to their diameter. Prevalence (%) was calculated by dividing
the total number of arteries within the specified diameter range by the
number of isthmus sections.16 Only arteries .0.25 mm in diameter and
,5 mm from the endocardium are included. Embedded: in direct
contact with atrial myocardium.
Figure 5 Major obstacles in the various sections. The prevalence (%
scale, left abscissa) of a muscular sleeve around the vein decreases
whereas that of the RCx increases from proximal to distal sections. Also
plotted (mm scale, right abscissa) is the maximum ‘myocardial depth’,
defined as the maximum distance between the endocardium and the
most subepicardial muscle fibres (not including the myocardial venous
sleeve) measured over the complete length of each section, with its standard deviation (vertical bars).
The histological data allowed for selecting the optimal
location(s) for an ablation line through the isthmus area
in the individual patients using arbitrary limits for the
distance between endocardium and RCx (5 mm),
maximum myocardial depth (5 mm), and the presence
or absence of a muscular sleeve around the vein that
was connected to atrial myocardium. With these criteria,
isthmus block could have been created safely and
successfully 10 mm distal to the isthmus in 9/15 patients,
at the isthmus in 10/16 patients, 10 mm proximal to
the isthmus in 5/16 patients, 20 mm proximal to the
Ablation for atrial fibrillation is mainly carried out in the
left atrium and an understanding of left atrial anatomy
and pulmonary veno-atrial junctions is helpful to electrophysiologists. Anatomically, the left atrium comprises
four components: septum, appendage, vestibule, and
venous component.17 The vestibular component is the
atrial wall leading to, and terminating in, the hinge line
(annulus) of the mitral valve. In recent years, a linear
lesion has been added in a part of the vestibule, the
so-called mitral isthmus, as part of the catheter ablation
strategy for atrial fibrillation. Although the vestibular
component is generally smooth on the endocardial
surface and appears simple in composition, our study
shows that there are features that may affect the rate
of success in creating a transmural lesion line through
the isthmus or, conversely, result in complications
should too much energy be deployed. Applying the
nomenclature of Cosio et al. 18 in fluoroscopic left
anterior-oblique projection, the isthmus is estimated
to lie adjacent to the posterior sector of the left
atrioventricular junction. With the index cut at the
isthmus, the cut distal to the index is at 10 mm superior
while the proximal cuts are inferior in attitudinal
orientation.
At all five section levels, the myocardium was relatively thin near the annulus. There, relatively low radio
frequency (RF) power should theoretically suffice to
create transmural lesions and problems in creating
conduction block in that area are therefore most likely
due to poor tissue contact or catheter instability. The
maximum myocardial depth was most often found
approximately in the middle of the sections, predominantly close to and above the vein. Besides relatively
thick myocardium, other structures may complicate or
impede the creation of conduction block by catheter
ablation.19,20 This includes (i) a myocardial sleeve
around the vein, continuous with atrial myocardium
that may bridge an endocardial lesion line, (ii) an RCx
in intimate contact with atrial myocardium that may be
damaged by RF ablation, (iii) local cooling of atrial myocardium by the above-mentioned vessels and by other
atrial arteries and veins, and (iv) crevices in the
isthmus area that may entrap the tip of the ablation catheter. While open flush, irrigated ablation electrodes may
be safer than conventional electrodes by preventing
protein aggregation and coagulum formation, the lack
of temperature feedback may impose certain risks.
When the tip of the ablation electrode is entrapped in
one of the crevices in the isthmus (Figures 1 and 3B ),
the delivery of nominal RF power levels without
temperature feedback may lead to steam explosions
within the thin atrial wall and pericardial effusion.21,22
Our serial sectioning demonstrates that the muscular
venous sleeve and relatively thick myocardium are the
694
main obstacles with a too proximal position of the ablation line, while the RCx may be at risk with a more
distal position of the line (Figure 5, Tables 1 and
2 ).23–26 The optimal location for the creation of isthmus
conduction block varied between patients. Within the
40-mm wide area that was investigated, endocardially
applied lesions of 5 mm depth would suffice to safely
and successfully create an isthmus block in 60, 63, 31,
6, and 0% at 10 mm distal to the isthmus, in the isthmus,
and at 10, 20, and 30 mm proximal to the isthmus,
respectively (Table 2 ). In 3/16 patients, the creation of
isthmus block by endocardial RF application may have
been very difficult due to the presence of an obstacle
throughout the complete isthmus area that was investigated. While a proximal location of the ablation line will
be safer by avoiding the RCx, such a procedure will
often require ablation from inside the vein due to the presence of a myocardial sleeve around this vein.
Recently, Becker15 studied the gross morphological features of the isthmus section in 20 patients. Contrary to
his findings, our histological assessment revealed thickest
atrial wall midway, with tapering at either end of the
isthmus. This study also described the isthmus as a watershed area between right coronary artery and left circumflex coronary arteries. Our serial sectioning, however,
demonstrates that the prevalence of major coronary
arteries decreased from distal to proximal sections, and
thus the likelihood of arterial damage would decrease
with a more proximal location of the ablation line. In
addition, the prevalence of atrial arteries did not differ
between the various sections although it appeared to
be somewhat lower in the section 10 mm proximal to
the isthmus. During an ablation procedure, one is
usually not informed about the extension of the myocardial sleeve around the vein, the thickness of atrial myocardium, or about the presence and position of
important arteries. Preferably, the creation of isthmus
block should be attempted as far as possible from the
RCx, but just distal to the end of the complete sleeve.
When the sleeve is incomplete at its distal end, ablation
of such a sleeve does not appear to be necessary for
obtaining isthmus block because the histological images
suggest that such incomplete sleeves are not connected
to the myocardial wall.
Our study confirms the observation of Becker15 is that
the CS and great cardiac vein do not mark the annulus.
In the area that was studied (5 cuts ¼ 40 mm), the vein
runs at the atrial side of the annulus at a distance that
increased from 6 mm in the most distal section to
11 mm in the most proximal section (Table 1 ). This
slanted course corresponds to an angle of 78 relative to
the annulus, and this angle appears small enough to
allow for estimation of the direction of the shortest
connection line between LIPV ostium and mitral annulus.
Atrial arteries that are fully embedded in atrial
myocardium are likely to be damaged by transmural
ablations. Such ablations may then affect more atrial
myocardium than the ablation line itself and one might
speculate that this could contribute to the late curative effect of left atrial lesions in patients with atrial
fibrillation.27
F.H.M. Wittkampf et al.
Study limitations
Although the heart specimens were not from patients
with atrial fibrillation, the size of the left atrium was
within normal range and comparable to patients with
idiopathic atrial fibrillation, the patient group usually
treated with catheter ablation. We acknowledge that
the relevance of our observations to catheter ablation
is necessarily speculative, but we think it is important
to draw attention to the variability in the structure of
the mitral isthmus and its vicinity.
Conclusions
The muscle sleeve around the CS and an RCx close to
the endocardial surface are the two major limiting
factors for the creation of mitral isthmus conduction
block by catheter ablation. On average, the distal end
of the sleeve terminates 10 mm proximal to the shortest connecting line between the LIPV and mitral
annulus. The RCx, approaching superiorly, may reach
the isthmus and be ,5 mm from the endocardium
in 30% of patients. The optimal location for the creation
of mitral isthmus conduction block differs between
patients. The highest success rates may be expected
at the isthmus and 10 mm distal to the isthmus, but
cooling by the RCx blood flow and/or damage to this
artery may complicate such a procedure at either
location. A more proximal location of the ablation line
will lower the risk of arterial damage, but may require
ablation from inside the vein in a high number of
patients. Important atrial arteries are often present in
the isthmus area. Isthmus ablation and arterial
damage may thus affect more atrial myocardium than
the ablation line itself. Small crevices, present in the
isthmus area in almost all patients, can entrap the tip
of the ablation catheter, which may lead to excessive
tissue heating and tamponade.
Acknowledgements
The authors are grateful to Pieter Doevendans for his
help with the preparation of this manuscript.
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