Preferential Conduction Properties Along The Left Lateral Ridge And The Arrhythmogenicity Of The Left Pulmonary Veins In Patients With Atrial Fibrillation
Toshiya Kurotobi, MD PhD, Yoshihisa Shimada, MD PhD, Naoto Kino, MD, Kazato Ito, MD, Kosuke Takehara, MD, Daisuke Tonomura, MD, Tomohiro Nakashoji MD, Kentaro Yano, MD, Chiharu Tanaka, MD, Masataka Yoshida, MD,PhD, Takao Tsuchida, MD PhD, Hitoshi Fukumoto, MD PhD
Caridiovascular Division Shiroyama Hospital, Habikino, Habikino City, Osaka, Japan.
Purpose: In this study, we examined the hypothesis that the preferential conduction property along left lateral ridge (LLR) might affect the arrhythmogenicity of left pulmonary veins (LPVs).
Methods: The study population included 40 consecutive AF patients. Radiofrequency energy (RF) was sequentially delivered along the LLR from a lower to upper manner during postero-lateral CS pacing during an isoproterenol infusion.
Results: The conduction time during pacing from the CS was significantly prolonged during radiofrequency (RF) deliveries (before vs. after, upper; 91±26ms vs. 127±38ms, p<0.001, lower; 86±21ms vs. 103±22ms, p<0.001). Remarkable prolongation of more than 30ms was observed in 19 of 40 patients (48%) (both LPVs, 6; only the upper LPVs, 12; and only the lower LPV, 1). Sites with a remarkable prolongation were observed at the carina between the LPVs,4 anterior site of the upper LPV carina,10 anterior wall of the lower LPV,3 and bottom of the lower LPVs 2 Thirty-three arrhythmogenic foci (AMF) from the LPVs were observed in 23/40 patients (56%). The conduction time during pacing from the LPVs during the RF delivery was significantly longer in the patients with AMF from the upper LPV than in those patients without (107±36ms vs. 146±40ms, p<0.01).
Conclusion: The LLR includes the preferential conduction properties between the CS and LPVs, and the observation of the serial changes during the RF delivery could provide us information about the LPVs arrhythmogenicity
Key Words : Marshall Bundle, Coronary Sinus, Atrial Fibrillation, Catheter Ablation.
Corresponding Address : Toshiya Kurotobi, MD, PhDCaridiovascular Division Shiroyama Hospital 2-8-1, Habikino, Habikino City, Osaka, 583-0872, Japan.
The Left lateral ridge (LLR) between left atrial appendage and left pulmonary veins (LPVs) showed a fiber orientation perpendicular to LPVs ostium, and it includes the ligament and vein of Marshall with the ganglia and fibers of the autonomic nervous system. The ligament and vein of Marshall containing the Marshall bundle (MB) with richly innervates the sympathetic and parasympathetic nerves can serve as a source of triggers and the substrate of reentry of atrial fibrillation (AF).1,2
Histological studies indicated that the proximal portion of the MB directly connects to the muscular sleeve of the CS, and the distal portion connects to the left atrial wall along the LLR and LPVs with wide variations.3,4 Because the dominant electrical connections and the conduction of the MB could serve as substrates for reentry as well arrhythmogenicity, the change of activation pattern along the LLR during radiofrequency application (RF) may be associated with the arrhythmogenicity of the LPVs. Actually, our previous study confirmed that the sites of AF initiation can be identified by using the angiographic vein of Marshall with balloon-occluded venography of CS during isoproterenol infusion.5 In this study, we examined the relationship between the conduction properties along LLR and the arrhythmogenicity of the LPVs.
The study population consisted of 40 out of 47 consecutive patients with drug-refractory AF episodes who underwent radiofrequency catheter ablation (CA). Seven patients were excluded because sinus rhythm could not be maintained during the RF ablation. Exclusion criteria for the patient characteristics were as follows, 1) a left atrial diameter (LAD) of more than 50mm, 2) significant valvular disease requiring surgery, 3) an ejection fraction of less than 40%, 4) hypertrophic obstructive cardiomyopathy, and 5) long lasting AF of more than 5 years. The patients’ mean age was 63 years, 29 (73%) were male, and 8 (20%) had persistent AF. Persistent AF was defined as that lasting longer than 7 days, not self-terminating and usually requiring medical intervention. Structural heart disease consisted of 10 patients (25%). The mean period of suffering from an AF episode was 55 months. The mean left atrial diameter was 39.6±5.6 mm, and left ventricular ejection fraction was 60.1±13.0%.
All antiarrhythmic drugs were generally discontinued for at least 3
days before the CA. All patients provided written informed consent
for the electrophysiological study and CA.
(N=23)||AMF (-) (n=17)||p value
|AF periods (months)||5.5±5.4||6.4±8.4||0.596|
|Diabetes Mellitus (%)||17||12||0.452|
|History of HF (%)||13||18||0.624|
|History of CI (%)||9||12||0.774|
|Left atrial diameter (mm)|
HF; heart failure, CI; cerebral infarction, A-P; anterior-posterior, S-L; septal- lateral, PV-MV; pulmonary veins-mitral valve
Electrophysiological Study And Catheter Ablation
A single 3000 IU bolus of heparin was administered and then an
activated clotting time of >300 seconds was maintained after the
transseptal puncture. A 20-pole diagnostic catheter was positioned in
the CS for pacing and recording. A 20-pole catheter was placed in the
right atrium to cover the area along the crista terminalis or superior
vena cava (SVC). The LA and PVs were accessed by a transseptal
approach. We introduced 3 steerable catheters, including two spiral
curve catheters, into the left atrium through a single transseptal
puncture site. The upper and lower LPVs were simultaneously
mapped with two adjustable 20-pole catheters (OPTIMA, Irvine,
USA) (Figure 1).
Catheter locations Twenty-pole adjustable circular catheters (OPTIMA, St. Jude Medical, Minneapolis, Minnesota, USA) were simultaneously positioned at the upper and lower LPVs. A 20-pole catheter was positioned in the CS, and the SVC and crista terminalis were covered with a 20 pole catheter. The roving catheter was initially positioned around the LPVs. The white arrow indicates the location of the pacing site during RF.
Coronary angiography was performed to evaluate the junction of
the CS and great cardiac vein to identify in the orifice of Marshall
vein and ligament. The features of the CS were determined by a
subsequent filling and staining with contrast and/or by noting
the location of the multipolar electrodes of the catheter within
the CS. The 3D constructed geometry of the entire left atrium
including the LPVs and LLR was created by using a NavX system
(St. Jude Medical, St. Paul, Minnesota, USA). At first RF energy
during CS pacing was delivered along the LLR as a part of the
LPV ablation (Figure 2), and each ablation site and the conduction
pattern during the RF delivery were monitored and recorded by
fluoroscopy and a 3D electroanatomical system. The surface ECG
and intracardiac electrograms filtered between 30 to 500 Hz were
recorded simultaneously with a polygraph (Cardiolab; GE, USA or
EP workmate; SJM, USA).
The schema of the RF delivery along the LLR during CS pacing. The pacing site during the RF application was delivered from the postero-lateral CS, possibly from the take-off site of the MB. The RF application along the LLR was sequentially delivered in a lower to upper manner (from the bottom of the inferior LPV, anterior wall of the inferior LPV, and LPV carina, to the anterior wall of the superior LPV) during CS pacing.
Radiofrequency (RF) energy was delivered for 30 to 60 seconds
at each site using a dumbbell shaped 8 mm tip (Japan Life Line,
Fantasista, Tokyo, Japan) or 3.5-mm irrigation tip catheter (St.
Jude Medical, Minneapolis, Minnesota, USA). The RF energy was
delivered with a power of 35 W with 8-mm-tip catheters, and 30 W
with 3.5-mm-tip catheters.
AF initiation and the prolongation of the upper LPV potentials during the RF delivery. AF was initiated from the left upper PV during CS pacing. The early activated reversed double potentials represent arrhythmogenic foci from the upper LPV (a). AF was spontaneously terminated during the RF application on the anterior wall of carina, and the interval from the CS pacing site to the upper LPV suddenly prolonged at the earliest activation site (pre, 53ms vs., post, 105ms) (b). PV; pulmonary vein potential, A; atrial potential
The Detection Of Arrhythmogenic FOCI
An isoproterenol (ISP) infusion (0.5-2μg/min) was administered to determine the arrhythmogenicity of the LPVs during the left PV
ablation. If AF persisted or spontaneously occurred under the ISP
infusion, we attempted to cardiovert the AF up to 3 times. The DC
energy was delivered with an external biphasic wave form of up to
Arrhythmogenic foci (AMF) were detected using our previously
reported methods. In summary, we simultaneously used five multipolar
catheters to record the electrograms from the LPVs to search for any
AMF. A 20-pole catheter (2 mm inter-electrode spacing) covered
the area from the SVC to the crista terminalis, and the coronary sinus
in addition to the ostium of the left PVs.6 AMF were defined as
direct AF triggers or spontaneous reproducible atrial premature beats
with coupling intervals of < 350ms or frequent repetitive firings. The
earliest activated sites were determined according to the sequence
and time difference recoded by multipolar catheters. The early
activated double potentials of the AMF from the PVs and SVC were
reversed, and we considered that those AMF originated from each
site. If the AMF were suspected to have originated from a non-PV
area uncovered by the catheters, we attempted to search the location
with a roving catheter around the early centrifugal activated sites.
The continuous variables are expressed as the mean±SD. The
variables were compared by a t-paired test or chi-square test. The data
without a normal distribution were compared by a Mann–Whitney
U test, which was used for the non-parametric analysis. A P<0.05
was considered statistically significant. All analyses were performed
using SPSS 10.0 statistical software (SPSS Inc., Chicago, IL, USA).
The change in the conduction properties during ablation along the
left lateral ridge
The earliest activated site of the upper LPV during CS pacing was
observed at the carina lesion in 32 of 40 patients (80%), anterior wall
in 4 of 40 (10%), and posterior wall in 4 of 40 (10%). The earliest
activated site was at the upper LPV in 34 of 40 (85%), bottom of the
lower LPV in 4 of 40 (10%), and posterior site in 2 of 40 (5%).
After the RF delivery along the LLR, the PV potentials of the upper LPV completely disappeared in one patient and that of the
lower LPV in 2 patients. The conduction time between the LPVs
and CS stimulus site was significantly prolonged during the RF
delivery (before vs. after, upper; 91±26 ms vs. 127±38 ms, p<0.001,
lower; 86±21ms vs. 103±22ms, p<0.001). A remarkable prolongation
of more than 30 ms was observed in 19 of 40 patients (48%) (both
LPVs; 6, only the upper LPVs; 12, and only the lower LPV; 1). The
sites of the remarkable prolongation during the RF delivery were
observed at the carina between the LPVs,4 anterior site of the upper
LPV carina,10 anterior wall of the lower LPV,3 and bottom of the
lower LPVs2 (Figure 3).
The Features Of The Arrhythmogenic Foci And Their
Relationship To The Conduction Properties
Thirty-three AMF from LPVs (upper; 22, lower; 11) were observed
in 23/40 patients 56%. Fifteen of the detected AMF directly shifted
to AF, and 16 of them exhibited premature atrial contractions and/or
transient frequent repetitive firings.
The patient characteristics in the patients with AMF and without
AMF are shown in Table 1. There were no significant differences in
the gender, age, AF period, hypertension, diabetes mellitus, history of
heart failure, history of cerebral artery disease, left atrial parameters,
and left ventricular ejection fraction, between the two groups.
The earliest activated site of the AMF from the upper LPV was
found at the carina region in 12 of 22[55%], anterior wall in 3 of
22[14%], roof site in 3 of 22[14%], and posterior wall in 4 of 22. The
earliest activated site of the AMF from the lower LPV was found at
the carina region in 6 of 11 [55%] anterior wall in 2 of 1,18% bottom
in 1 of 11[9%], and posterior wall in 2 of 11[18%].
The conduction time from the CS to the earliest activated upper
PV after the RF delivery was significantly longer in the patients with
AMF from the upper LPV than in those patients without (107±36 ms
vs. 146±40 ms, p<0.01), and the conduction time from the CS pacing
site to the earliest activation site of the upper LPV was significantly
prolonged in the patients with AMF than in those without during
the RF delivery (44±22ms vs. 17±11ms, p<0.01). The following AF
after AMF was spontaneously terminated in 2 of 15 AF episodes 13%during RF along LLR, and the prolonged conduction time after
RF along LLR were 47 ms and 44 ms, respectively. The premature
atrial contractions and/or transient frequent repetitive firings were no
more observed after RF along LLR in 11 of 16[69%].
In this study, the dominant conduction from the CS to the
upper LPV was commonly observed in the carina region with its
increased arrhythmogenicity. The conduction time between those
was significantly prolonged during the RF deliveries along the LLR,
and a remarkable jump prolongation of more than 30 ms in those
was observed in approximately half of the patients. The extent of the
prolongation was significantly higher in the patients with AMF, as
compared to the patients without AMF. Thus, these findings could
imply that the LLR containing the MB includes the preferential
conduction properties between the CS and LPVs, and has an
association with the increased arrhythmogenicity of the upper LPV.
The observation of the change in the conduction properties during
the RF delivery could provide us with useful information about the
potential upper LPVs arrhythmogenicity.
Anatomical Myocardial Structure Of The Left Lateral Ridge
The LLR showed a fiber orientation perpendicular to the blood
flow, and the LPVs and left atrial musculature are likely to be
disconnected or was only connected via a narrow isthmus because
of the bulging ridge structure.7 There are abrupt changes in the fiber
orientation in the middle portion of the LPVs.
The VOM, or LOM as the MB including the density of the
ganglia and fibers of the autonomic nervous system, can be traced
on the epicardial aspect of the LLR with a close proximity to the
endocardial surface, and they course obliquely and superficially in the
ridge at variable distances from the endocardial surface of the LLR
within 3 mm from the endocardium. The other most dominant fiber
of the LLR is Bachmann’s bundle, which runs leftward to the neck
of the left atrial appendage on the epicardial aspect of the LLR with
a close relationship to the vein of Marshall or its ligament. Deeper
than Bachmann’s bundle is an another subepicardial fiber, which is
the septopulmonary bundle that covers the orifices of the left PVs.
Futhermore, the subendocardial septoatrial bundle forms a broad flat
bundle towards the orifices of the left PVs.
Arrhythmogenicity Of The Marshall Bundle
The Vein of Marshall or its ligament containing the MB is a
remnant of the left superior vena cava, and is accompanied with
richly innervated sympathetic and parasympathetic nerves, and its
arrhythmogenicity could be revealed during an ISP infusion.6,8, 9
In this study, AMF were highly observed from both LPVs under
an ISP infusion, and the earliest site of those from the LPVs was
often determined to be around the carina region. These observations
are likely to be consistent with the previous report.10 In addition,
the complex crossing of the muscular connections, bridges, neural
inputs, and the adjoining muscle sleeves, possibly related to the
MB conduction in the inter-PV carina, might promote electrical
arrhythmogenicity including spontaneous ectopies of AF.11 From
those observations, intensified RF applications targeting the carina
lesion and LLR should be required to delineate the arrhythmogenicity
of the MB because of its epicardial location.
Conduction Properties Of The Marshall Bundle
The electrical connections and the conduction of the MB could serve as substrates for reentry as well as arrhythmogenicity. The
MB runs along the LLR between the LAA and anterior wall of
the LPVs. The proximal portion of the MB directly connects to the
muscle sleeve of the CS, and the distal end of that connects to the left
atrial wall and LPVs.3, 4, 12 Our recent case report confirmed that the
epicardial MB conduction could include a preferential conduction to
In this study, the RF application along the LLR suddenly and
remarkably prolonged the conduction time between the CS and
LPVs in approximately half of the patients, and these observations
might reflect the presence of a dominant longitudinal conduction
along the LLR. And then, the earliest activated site of the upper
LPVs during CS pacing was highly observed around the carina
region, and also a remarkable prolongation jump during the RF
delivery was highly observed around the carina and/or adjacent
anterior area. A previous report suggested that the distal exit of the
MB into the upper LPV is commonly located around the inter-PV
junction, possibly bypassing the LPV junction to the left atrium.7
These specific muscle orientations and the dominant MB conduction
toward the carina region could promote the preferential conduction
Recent studies demonstrated that the carina region should be the
target site to achieve complete LPV-LA disconnection whether using
circumferential or wide encirclement ablation strategies,14, 15 and
the additional ablation at the PV carina region may be sometimes
required to achieve electrical isolation even after PVI.16, 17 In addition,
the ablation of PV carina region may be associated with the improved
outcome of AF ablation.18, 19 These reports consistently imply that the
carina region can be a favorable target for an AF ablation strategy. In
the meantime, we have to keep in mind that an excessive multiple
RF energy toward carina may increase the risk of PV stenosis, and
the careless catheter manipulation along LLR from LAA side may
be prone to increase the risk of cardiac perforation, because the LAA
has a very thin wall structure.
LPV Arrhythmogenicity And Prolonged Conduction
In this study, the prolongation of the conduction time between
the CS and LPVs during the RF delivery was significantly more
commonly observed in patients with upper LPV arrhythmogenic
foci than in those without. The preferential properties of the MB
connecting to the LPVs might involve cross-talk that promotes an increased LPV arrhythmogenicity.3, 4, 12 Previous reports
demonstrated that the presence of an LSVC and larger VOM were
likely to be related to the increased chance of AF.9, 20 and thus a larger
amount of preserved MB muscle as a remnant of the LSVC, which is
related to the conduction properties of the LPVs, may be crucial for
determining the increased arrhythmogenicity of the LPVs.
CS pacing could not only capture the MB, but also atrial muscle.
In addition, we could not directly record the MB potentials. When
the rapid conduction endocardially traveled through atrium muscle,
the interpretation of MB conduction could be limited. A previous
study reported that the PV muscle covers a large extent of the PV
perimeter, and there are specific breakthroughs from the left atrium.21
If the continuous MB conduction is present, careful 3D mapping
system should be required to assess the preferential conduction
properties via the MB.
MB predominant conduction properties during the RF delivery
could provide us with useful information about the potential upper
LPV arrhythmogenicity. These findings imply the necessity for
intensified RF applications in the carina region and entire LLR.